Psoriasis Collection

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

health_insurance_web.jpg

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

health_insurance_web.jpg

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

health_insurance_web.jpg

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Injecting Vaccine_web.jpg

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Injecting Vaccine_web.jpg

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Injecting Vaccine_web.jpg

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

A version of this article first appeared on Medscape.com.

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

A version of this article first appeared on Medscape.com.

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

A version of this article first appeared on Medscape.com.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

self_injection_web.jpg

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

Gelfand_Joel_web.jpg

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

[embed:render:related:node:228614]

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Hanauer_Stephen_B_CHICAGO_web.jpg

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

self_injection_web.jpg

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

Gelfand_Joel_web.jpg

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

[embed:render:related:node:228614]

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Hanauer_Stephen_B_CHICAGO_web.jpg

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

self_injection_web.jpg

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

Gelfand_Joel_web.jpg

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

[embed:render:related:node:228614]

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Hanauer_Stephen_B_CHICAGO_web.jpg

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

[embed:render:related:node:244983]

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Ritchlin_Christopher_NY_web2.jpg

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

144542_Gelfand_Joel_web.JPG

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

[embed:render:related:node:242060]

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

[embed:render:related:node:244983]

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Ritchlin_Christopher_NY_web2.jpg

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

144542_Gelfand_Joel_web.JPG

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

[embed:render:related:node:242060]

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

[embed:render:related:node:244983]

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Ritchlin_Christopher_NY_web2.jpg

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

144542_Gelfand_Joel_web.JPG

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

[embed:render:related:node:242060]

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

A version of this article first appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

A version of this article first appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

A version of this article first appeared on Medscape.com.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

money_pills_web.jpg

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

[embed:render:related:node:221333]

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

money_pills_web.jpg

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

[embed:render:related:node:221333]

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

money_pills_web.jpg

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

[embed:render:related:node:221333]

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

Armstrong_April_LA_web.jpg

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

[embed:render:related:node:232580]

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

Garg_Amit_NY_web.jpg

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

[embed:render:related:node:241185]

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

Armstrong_April_LA_web.jpg

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

[embed:render:related:node:232580]

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

Garg_Amit_NY_web.jpg

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

[embed:render:related:node:241185]

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

Armstrong_April_LA_web.jpg

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

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IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

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He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

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In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

[embed:render:related:node:226491]

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

[embed:render:related:node:226491]

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

[embed:render:related:node:226491]

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.