Neil Osterweil

The question of whether primary transoral surgery or radiation is a better treatment deescalation option for patients with low-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is still unanswered, despite the best efforts of investigators in the randomized phase 2 ORATOR2 trial.

Transoral surgery was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, the study found.

The trial, begun in early 2018, was halted in late 2020 because of safety concerns after 2 of 31 patients randomized to surgery died from treatment-related causes.

But the story doesn’t end there, investigators and observers say.

In both trial arms, patients had good swallowing outcomes and other favorable quality-of-life measures at 1 year, and it’s too early to tell whether the transoral surgery (TOS) was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, wrote investigators Daniel A. Palma, MD, from Western University in London, Ontario, and colleagues in JAMA Oncology.

Nonetheless, “the results of this randomized clinical trial suggest that a primary [surgery] approach was associated with an up-front risk of treatment-related mortality, and caution is warranted with this approach,” the investigators wrote.
 

Hard to interpret

“It’s challenging to do that study in Canada, frankly, and it’s hard to make much of it, with the trial being terminated early,” said Neil D. Gross, MD, a head and neck cancer surgeon-scientist with MD Anderson Cancer Center, Houston, in an interview.

Dr. Gross and Sewit Teckie, MD, system chief of radiation oncology at NYC Health and Hospitals, cowrote an editorial accompanying the ORATOR2 results that was published in JAMA Oncology.

“There’s a huge difference in the volume of transoral robotic surgery performed in the United States, compared with Canada – it’s night and day, and that’s due to the different kind of healthcare systems that we have,” Dr. Gross said.

[embed:render:related:node:250329]

As he and Dr. Teckie noted, the combined mortality rate for surgical patients in the multicenter ORATOR2 and the earlier ORATOR trial, which was not limited to patients with HPV-related cancers, was 3.6%.

In contrast, in the ECOG-ACRIN 3311 trial comparing standard radiation with reduced dose radiation following TOS in patients with intermediate-risk HPV-positive oropharynx cancer, there was only one death among 495 patients, for a mortality rate of 0.2%.

“In the United States, mortality after transoral robotic surgery compares favorably with nonsurgical treatment and is lowest at high-volume centers. ORATOR2 also mandated prophylactic tracheostomy, a practice rarely used in contemporary transoral surgery for low-risk HPV-related OPSCC,” the authors wrote.

In defense of surgery

In an interview posted on the JAMA Network website, ORATOR2 co-investigator Anthony C. Nichols, MD, from the department of otolaryngology, head and neck surgery at Western University, London, Ontario, said that despite the findings of ORATOR2, transoral surgery is a good option for patients with low-risk disease and favorable anatomy.

“When you even look at the subset of these early T-stage patients that have anatomy that’s favorable towards transoral surgery, they do better. Their burden of disease is smaller, there’s less extensive neck disease ... so what happens very frequently, including even in the discussion of ECOG-ACRIN 3311, is comparisons to these large cooperative group studies that include T3, T4 tumors that no one on the planet would think about removing transorally,” he said.

“Everyone focuses on the surgical stopping, but what we should also focus on is how outstanding the patients did in the RT arm in both these studies,” he added.

Dr. Nichols also noted that quality-of-life metrics for patients randomized to surgery are comparable with those of patients randomized to radiation and that swallowing outcomes with surgery may be superior.

“In our minds, I think the issue is resolved, and we’re just moving on to the next concept, and the debate will rage on,” he said.
 

ORATOR2 study methodology

The primary endpoint of the trial was OS, compared with historical controls, with secondary endpoints of PFS, quality of life, and toxicity.

A total of 30 patients were randomized to receive RT, and 31 to receive TOS and neck dissection, with adjuvant reduced-dose RT depending on pathologic findings.

At a median follow-up of 17 months, there were 3 deaths in the surgery arm, including the 2 previously mentioned patients who died from treatment-related causes at 0.7 and 4.3 months after randomization, and 1 patient who died from myocardial infarction at 8.5 months. As noted before, OS and PFS data were not mature at the time of study termination.

Quality of life and functional outcomes were generally similar between the trial arms, except for worse scores among patients randomized to TOS and neck dissection in subdomains of coughing and weight loss on the European Organisation for Research and Treatment of Cancer H&N35 scale.

The trial was supported by an Ontario Institute for Cancer Research clinician-scientist operating grant and Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers Fund. Dr. Nichols reported grants from Novartis Canada outside the submitted work. Dr. Gross reported grants and personal fees from Regeneron, personal fees from Sanofi-Genzyme, Intuitive Surgical, and DragonFly Therapeutics, as well as advisory board service for PDS Biotechnology, Shattuck Labs, and Sanofi-Genzyme outside the submitted work.

The question of whether primary transoral surgery or radiation is a better treatment deescalation option for patients with low-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is still unanswered, despite the best efforts of investigators in the randomized phase 2 ORATOR2 trial.

Transoral surgery was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, the study found.

The trial, begun in early 2018, was halted in late 2020 because of safety concerns after 2 of 31 patients randomized to surgery died from treatment-related causes.

But the story doesn’t end there, investigators and observers say.

In both trial arms, patients had good swallowing outcomes and other favorable quality-of-life measures at 1 year, and it’s too early to tell whether the transoral surgery (TOS) was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, wrote investigators Daniel A. Palma, MD, from Western University in London, Ontario, and colleagues in JAMA Oncology.

Nonetheless, “the results of this randomized clinical trial suggest that a primary [surgery] approach was associated with an up-front risk of treatment-related mortality, and caution is warranted with this approach,” the investigators wrote.
 

Hard to interpret

“It’s challenging to do that study in Canada, frankly, and it’s hard to make much of it, with the trial being terminated early,” said Neil D. Gross, MD, a head and neck cancer surgeon-scientist with MD Anderson Cancer Center, Houston, in an interview.

Dr. Gross and Sewit Teckie, MD, system chief of radiation oncology at NYC Health and Hospitals, cowrote an editorial accompanying the ORATOR2 results that was published in JAMA Oncology.

“There’s a huge difference in the volume of transoral robotic surgery performed in the United States, compared with Canada – it’s night and day, and that’s due to the different kind of healthcare systems that we have,” Dr. Gross said.

[embed:render:related:node:250329]

As he and Dr. Teckie noted, the combined mortality rate for surgical patients in the multicenter ORATOR2 and the earlier ORATOR trial, which was not limited to patients with HPV-related cancers, was 3.6%.

In contrast, in the ECOG-ACRIN 3311 trial comparing standard radiation with reduced dose radiation following TOS in patients with intermediate-risk HPV-positive oropharynx cancer, there was only one death among 495 patients, for a mortality rate of 0.2%.

“In the United States, mortality after transoral robotic surgery compares favorably with nonsurgical treatment and is lowest at high-volume centers. ORATOR2 also mandated prophylactic tracheostomy, a practice rarely used in contemporary transoral surgery for low-risk HPV-related OPSCC,” the authors wrote.

In defense of surgery

In an interview posted on the JAMA Network website, ORATOR2 co-investigator Anthony C. Nichols, MD, from the department of otolaryngology, head and neck surgery at Western University, London, Ontario, said that despite the findings of ORATOR2, transoral surgery is a good option for patients with low-risk disease and favorable anatomy.

“When you even look at the subset of these early T-stage patients that have anatomy that’s favorable towards transoral surgery, they do better. Their burden of disease is smaller, there’s less extensive neck disease ... so what happens very frequently, including even in the discussion of ECOG-ACRIN 3311, is comparisons to these large cooperative group studies that include T3, T4 tumors that no one on the planet would think about removing transorally,” he said.

“Everyone focuses on the surgical stopping, but what we should also focus on is how outstanding the patients did in the RT arm in both these studies,” he added.

Dr. Nichols also noted that quality-of-life metrics for patients randomized to surgery are comparable with those of patients randomized to radiation and that swallowing outcomes with surgery may be superior.

“In our minds, I think the issue is resolved, and we’re just moving on to the next concept, and the debate will rage on,” he said.
 

ORATOR2 study methodology

The primary endpoint of the trial was OS, compared with historical controls, with secondary endpoints of PFS, quality of life, and toxicity.

A total of 30 patients were randomized to receive RT, and 31 to receive TOS and neck dissection, with adjuvant reduced-dose RT depending on pathologic findings.

At a median follow-up of 17 months, there were 3 deaths in the surgery arm, including the 2 previously mentioned patients who died from treatment-related causes at 0.7 and 4.3 months after randomization, and 1 patient who died from myocardial infarction at 8.5 months. As noted before, OS and PFS data were not mature at the time of study termination.

Quality of life and functional outcomes were generally similar between the trial arms, except for worse scores among patients randomized to TOS and neck dissection in subdomains of coughing and weight loss on the European Organisation for Research and Treatment of Cancer H&N35 scale.

The trial was supported by an Ontario Institute for Cancer Research clinician-scientist operating grant and Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers Fund. Dr. Nichols reported grants from Novartis Canada outside the submitted work. Dr. Gross reported grants and personal fees from Regeneron, personal fees from Sanofi-Genzyme, Intuitive Surgical, and DragonFly Therapeutics, as well as advisory board service for PDS Biotechnology, Shattuck Labs, and Sanofi-Genzyme outside the submitted work.

The question of whether primary transoral surgery or radiation is a better treatment deescalation option for patients with low-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is still unanswered, despite the best efforts of investigators in the randomized phase 2 ORATOR2 trial.

Transoral surgery was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, the study found.

The trial, begun in early 2018, was halted in late 2020 because of safety concerns after 2 of 31 patients randomized to surgery died from treatment-related causes.

But the story doesn’t end there, investigators and observers say.

In both trial arms, patients had good swallowing outcomes and other favorable quality-of-life measures at 1 year, and it’s too early to tell whether the transoral surgery (TOS) was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year, wrote investigators Daniel A. Palma, MD, from Western University in London, Ontario, and colleagues in JAMA Oncology.

Nonetheless, “the results of this randomized clinical trial suggest that a primary [surgery] approach was associated with an up-front risk of treatment-related mortality, and caution is warranted with this approach,” the investigators wrote.
 

Hard to interpret

“It’s challenging to do that study in Canada, frankly, and it’s hard to make much of it, with the trial being terminated early,” said Neil D. Gross, MD, a head and neck cancer surgeon-scientist with MD Anderson Cancer Center, Houston, in an interview.

Dr. Gross and Sewit Teckie, MD, system chief of radiation oncology at NYC Health and Hospitals, cowrote an editorial accompanying the ORATOR2 results that was published in JAMA Oncology.

“There’s a huge difference in the volume of transoral robotic surgery performed in the United States, compared with Canada – it’s night and day, and that’s due to the different kind of healthcare systems that we have,” Dr. Gross said.

[embed:render:related:node:250329]

As he and Dr. Teckie noted, the combined mortality rate for surgical patients in the multicenter ORATOR2 and the earlier ORATOR trial, which was not limited to patients with HPV-related cancers, was 3.6%.

In contrast, in the ECOG-ACRIN 3311 trial comparing standard radiation with reduced dose radiation following TOS in patients with intermediate-risk HPV-positive oropharynx cancer, there was only one death among 495 patients, for a mortality rate of 0.2%.

“In the United States, mortality after transoral robotic surgery compares favorably with nonsurgical treatment and is lowest at high-volume centers. ORATOR2 also mandated prophylactic tracheostomy, a practice rarely used in contemporary transoral surgery for low-risk HPV-related OPSCC,” the authors wrote.

In defense of surgery

In an interview posted on the JAMA Network website, ORATOR2 co-investigator Anthony C. Nichols, MD, from the department of otolaryngology, head and neck surgery at Western University, London, Ontario, said that despite the findings of ORATOR2, transoral surgery is a good option for patients with low-risk disease and favorable anatomy.

“When you even look at the subset of these early T-stage patients that have anatomy that’s favorable towards transoral surgery, they do better. Their burden of disease is smaller, there’s less extensive neck disease ... so what happens very frequently, including even in the discussion of ECOG-ACRIN 3311, is comparisons to these large cooperative group studies that include T3, T4 tumors that no one on the planet would think about removing transorally,” he said.

“Everyone focuses on the surgical stopping, but what we should also focus on is how outstanding the patients did in the RT arm in both these studies,” he added.

Dr. Nichols also noted that quality-of-life metrics for patients randomized to surgery are comparable with those of patients randomized to radiation and that swallowing outcomes with surgery may be superior.

“In our minds, I think the issue is resolved, and we’re just moving on to the next concept, and the debate will rage on,” he said.
 

ORATOR2 study methodology

The primary endpoint of the trial was OS, compared with historical controls, with secondary endpoints of PFS, quality of life, and toxicity.

A total of 30 patients were randomized to receive RT, and 31 to receive TOS and neck dissection, with adjuvant reduced-dose RT depending on pathologic findings.

At a median follow-up of 17 months, there were 3 deaths in the surgery arm, including the 2 previously mentioned patients who died from treatment-related causes at 0.7 and 4.3 months after randomization, and 1 patient who died from myocardial infarction at 8.5 months. As noted before, OS and PFS data were not mature at the time of study termination.

Quality of life and functional outcomes were generally similar between the trial arms, except for worse scores among patients randomized to TOS and neck dissection in subdomains of coughing and weight loss on the European Organisation for Research and Treatment of Cancer H&N35 scale.

The trial was supported by an Ontario Institute for Cancer Research clinician-scientist operating grant and Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers Fund. Dr. Nichols reported grants from Novartis Canada outside the submitted work. Dr. Gross reported grants and personal fees from Regeneron, personal fees from Sanofi-Genzyme, Intuitive Surgical, and DragonFly Therapeutics, as well as advisory board service for PDS Biotechnology, Shattuck Labs, and Sanofi-Genzyme outside the submitted work.

Young women with a new diagnosis of node-negative triple-negative breast cancer (TNBC) who have high levels of stromal tumor-infiltrating lymphocytes (sTILs) have a very good long-term prognosis, and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.

Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.

In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.

“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
 

Markers for immune response

Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.

For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).

“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
 

Retrospective study

To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.

Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,

During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.

The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.

“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.

The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.

Young women with a new diagnosis of node-negative triple-negative breast cancer (TNBC) who have high levels of stromal tumor-infiltrating lymphocytes (sTILs) have a very good long-term prognosis, and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.

Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.

In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.

“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
 

Markers for immune response

Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.

For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).

“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
 

Retrospective study

To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.

Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,

During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.

The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.

“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.

The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.

Young women with a new diagnosis of node-negative triple-negative breast cancer (TNBC) who have high levels of stromal tumor-infiltrating lymphocytes (sTILs) have a very good long-term prognosis, and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.

Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.

In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.

“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
 

Markers for immune response

Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.

For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).

“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
 

Retrospective study

To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.

Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,

During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.

The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.

“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.

The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.

In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.

Now, researchers at Harvard Medical School, Boston, report that patients with high-deductible health insurance plans are significantly more likely to have a delay in diagnosis of metastatic cancer, compared with patients with low-deductible plans.

Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.

After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.

“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
 

‘Deductible relief day’

Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.

This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.

“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.

High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.

In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
 

Insurance claims data

Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.

The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.

To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.

During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.

During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.

According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.

The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.

“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
 

Further evidence of a flawed system

The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.

“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.

“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.

The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.

“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.

In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.

Now, researchers at Harvard Medical School, Boston, report that patients with high-deductible health insurance plans are significantly more likely to have a delay in diagnosis of metastatic cancer, compared with patients with low-deductible plans.

Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.

After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.

“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
 

‘Deductible relief day’

Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.

This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.

“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.

High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.

In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
 

Insurance claims data

Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.

The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.

To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.

During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.

During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.

According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.

The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.

“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
 

Further evidence of a flawed system

The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.

“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.

“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.

The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.

“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.

In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.

Now, researchers at Harvard Medical School, Boston, report that patients with high-deductible health insurance plans are significantly more likely to have a delay in diagnosis of metastatic cancer, compared with patients with low-deductible plans.

Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.

After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.

“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
 

‘Deductible relief day’

Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.

This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.

“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.

High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.

In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
 

Insurance claims data

Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.

The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.

To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.

During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.

During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.

According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.

The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.

“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
 

Further evidence of a flawed system

The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.

“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.

“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.

The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.

“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

158969_OR_heart_transplant_web.jpg

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

158969_heart_in_liquid_web.jpg

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

158969_OR_heart_transplant_web.jpg

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

158969_heart_in_liquid_web.jpg

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

158969_OR_heart_transplant_web.jpg

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

158969_heart_in_liquid_web.jpg

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

van der Heijde_Desiree_NL_3_web.jpg

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

[embed:render:related:node:238207]

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

Proft_Fabian_GERMANY_web.jpg

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

van der Heijde_Desiree_NL_3_web.jpg

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

[embed:render:related:node:238207]

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

Proft_Fabian_GERMANY_web.jpg

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

van der Heijde_Desiree_NL_3_web.jpg

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

[embed:render:related:node:238207]

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

Proft_Fabian_GERMANY_web.jpg

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

Ramiro_Sofia_NETHERLANDS_2_web.jpg

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

Gensler_Lianne_CA2_web.jpg

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

Ramiro_Sofia_NETHERLANDS_2_web.jpg

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

Gensler_Lianne_CA2_web.jpg

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

Ramiro_Sofia_NETHERLANDS_2_web.jpg

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

Gensler_Lianne_CA2_web.jpg

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

Flatman_Leah_CANADA_web.jpg

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

Flatman_Leah_CANADA_web.jpg

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

Flatman_Leah_CANADA_web.jpg

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.

For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.

Topalovic_Marko_web.JPG

“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.

AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
 

Reading between the lines

In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.

“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.

Leon_William_web.JPG

“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
 

Putting it together

Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.

“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
 

AI Spirometry details

In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.

The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.

In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.

The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.

In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.

Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).

There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
 

Language processing details

Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.

The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.

The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.

For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.

The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).

The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.

SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.

For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.

Topalovic_Marko_web.JPG

“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.

AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
 

Reading between the lines

In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.

“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.

Leon_William_web.JPG

“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
 

Putting it together

Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.

“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
 

AI Spirometry details

In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.

The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.

In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.

The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.

In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.

Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).

There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
 

Language processing details

Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.

The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.

The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.

For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.

The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).

The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.

SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.

For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.

Topalovic_Marko_web.JPG

“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.

AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
 

Reading between the lines

In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.

“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.

Leon_William_web.JPG

“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
 

Putting it together

Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.

“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
 

AI Spirometry details

In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.

The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.

In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.

The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.

In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.

Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).

There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
 

Language processing details

Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.

The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.

The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.

For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.

The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).

The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

Mehta_Bella_NY_web.jpg

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

[embed:render:related:node:220615]

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

[embed:render:related:node:204230]

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

158295_graphic_web.png

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

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

Mehta_Bella_NY_web.jpg

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

[embed:render:related:node:220615]

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

[embed:render:related:node:204230]

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

158295_graphic_web.png

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

COPENHAGEN – Pregnant women with systemic lupus erythematosus (SLE) are at significantly higher risk of requiring transfusion, developing a cerebrovascular disorder, or developing acute renal failure than pregnant women without SLE, a review of data from an American national sample indicates.

Pregnant women with SLE also have a twofold-higher risk for premature delivery, and a threefold risk of having a fetus with intrauterine growth restriction than their pregnant counterparts without SLE, reported Bella Mehta, MBBS, MS, MD, a rheumatologist at the Hospital for Special Surgery in New York.

Mehta_Bella_NY_web.jpg

“Severe maternal morbidity and fetal morbidity still remain high, but this work can help inform physicians and counsel patients for pregnancy planning and management,” she said at the annual European Congress of Rheumatology.

Although in-hospital maternal and fetal mortality rates for women with SLE have declined over the past 2 decades, the same cannot be said for morbidities, prompting the investigators to conduct a study to determine the proportion of fetal and maternal morbidity in SLE deliveries, compared with non-SLE deliveries over a decade.

[embed:render:related:node:220615]

Inpatient Sample

Dr. Mehta and colleagues studied retrospective data on 40 million delivery-related admissions from the National Inpatient Sample database. Of these patients, 51,161 had a diagnosis of SLE.

They identified all delivery-related hospital admissions for patients with and without SLE from 2008 through 2017 using diagnostic codes.

The researchers looked at fetal morbidity indicators, including preterm delivery and intrauterine growth restriction, and used the Centers for Disease Control and Prevention standard definition of severe maternal morbidity as “unexpected outcomes of labor and delivery that result in significant short- or long- term consequences to a woman’s health.”

They identified 21 severe maternal morbidity outcomes, including blood transfusion requirements, acute renal failure, eclampsia and disseminated intravascular coagulation, cardiovascular and peripheral vascular disorders, and general medical issues (hysterectomy, shock, sepsis, adult respiratory distress syndrome, severe anesthesia complications, temporary tracheostomy, and ventilation).

[embed:render:related:node:204230]

Study results

Women with SLE were slightly older at the time of delivery (mean age, 30.05 vs. 29.19 years) and had more comorbidities, according to the Elixhauser Comorbidity Scale, with 97.84% of women in this group having one to four comorbidities, compared with 19.4% of women without SLE.

158295_graphic_web.png

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