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Ixekizumab found superior to ustekinumab in psoriasis at 24 weeks
ORLANDO – The interleukin-17A inhibitor ixekizumab was associated with superior efficacy and safety when compared with ustekinumab at 24 weeks, a head-to-head trial of the two monoclonal antibodies in plaque psoriasis has shown.
The 24-week data from the IXORA-S trial were presented during a late-breaking clinical trial session at the annual meeting of the American Academy of Dermatology by Kristian Reich, MD, PhD, a founder of SCIderm in Hamburg, Germany.
At 24 weeks, 49% in the ixekizumab arm achieved a Psoriasis Area and Severity Index (PASI) 100 level of skin clearance, compared with 24% in the ustekinumab arm (P = .001). Ixekizumab treatment also reached significantly higher skin clearances than ustekinumab at 24 weeks at the level of PASI 90 (83% vs. 59%; P less than .001) and PASI 75 (91% vs. 82%; P = .015).
Treatment with ixekizumab produced a Static Physician’s Global Assessment (sPGA) score of 0 in 54% at 24 weeks, compared with 24% with ustekinumab (P less than .001). A sPGA score of 0 or 1 occurred in 87% of patients who took ixekizumab and in 59% of the ustekinumab group.
An improvement of 4 or more points in the pruritus Numeric Rating Scale was reported by 86% of ixekizumab patients at 24 weeks, compared with 72% of those who took ustekinumab (P = .018).
Dr. Reich reported that there were no deaths or any significant differences in overall treatment-related adverse events across both arms, although he cautioned against putting too much stock in 24-week safety data. “I hesitate to show safety data for only 300 patients at 24 weeks, but it’s good to see here that there doesn’t seem to be a difference. I still would want to see larger patient numbers and more long-term data,” he said.
Dr. Reich had numerous disclosures, including honoraria for serving as a speaker for Eli Lilly, the sponsor of this trial.
ORLANDO – The interleukin-17A inhibitor ixekizumab was associated with superior efficacy and safety when compared with ustekinumab at 24 weeks, a head-to-head trial of the two monoclonal antibodies in plaque psoriasis has shown.
The 24-week data from the IXORA-S trial were presented during a late-breaking clinical trial session at the annual meeting of the American Academy of Dermatology by Kristian Reich, MD, PhD, a founder of SCIderm in Hamburg, Germany.
At 24 weeks, 49% in the ixekizumab arm achieved a Psoriasis Area and Severity Index (PASI) 100 level of skin clearance, compared with 24% in the ustekinumab arm (P = .001). Ixekizumab treatment also reached significantly higher skin clearances than ustekinumab at 24 weeks at the level of PASI 90 (83% vs. 59%; P less than .001) and PASI 75 (91% vs. 82%; P = .015).
Treatment with ixekizumab produced a Static Physician’s Global Assessment (sPGA) score of 0 in 54% at 24 weeks, compared with 24% with ustekinumab (P less than .001). A sPGA score of 0 or 1 occurred in 87% of patients who took ixekizumab and in 59% of the ustekinumab group.
An improvement of 4 or more points in the pruritus Numeric Rating Scale was reported by 86% of ixekizumab patients at 24 weeks, compared with 72% of those who took ustekinumab (P = .018).
Dr. Reich reported that there were no deaths or any significant differences in overall treatment-related adverse events across both arms, although he cautioned against putting too much stock in 24-week safety data. “I hesitate to show safety data for only 300 patients at 24 weeks, but it’s good to see here that there doesn’t seem to be a difference. I still would want to see larger patient numbers and more long-term data,” he said.
Dr. Reich had numerous disclosures, including honoraria for serving as a speaker for Eli Lilly, the sponsor of this trial.
ORLANDO – The interleukin-17A inhibitor ixekizumab was associated with superior efficacy and safety when compared with ustekinumab at 24 weeks, a head-to-head trial of the two monoclonal antibodies in plaque psoriasis has shown.
The 24-week data from the IXORA-S trial were presented during a late-breaking clinical trial session at the annual meeting of the American Academy of Dermatology by Kristian Reich, MD, PhD, a founder of SCIderm in Hamburg, Germany.
At 24 weeks, 49% in the ixekizumab arm achieved a Psoriasis Area and Severity Index (PASI) 100 level of skin clearance, compared with 24% in the ustekinumab arm (P = .001). Ixekizumab treatment also reached significantly higher skin clearances than ustekinumab at 24 weeks at the level of PASI 90 (83% vs. 59%; P less than .001) and PASI 75 (91% vs. 82%; P = .015).
Treatment with ixekizumab produced a Static Physician’s Global Assessment (sPGA) score of 0 in 54% at 24 weeks, compared with 24% with ustekinumab (P less than .001). A sPGA score of 0 or 1 occurred in 87% of patients who took ixekizumab and in 59% of the ustekinumab group.
An improvement of 4 or more points in the pruritus Numeric Rating Scale was reported by 86% of ixekizumab patients at 24 weeks, compared with 72% of those who took ustekinumab (P = .018).
Dr. Reich reported that there were no deaths or any significant differences in overall treatment-related adverse events across both arms, although he cautioned against putting too much stock in 24-week safety data. “I hesitate to show safety data for only 300 patients at 24 weeks, but it’s good to see here that there doesn’t seem to be a difference. I still would want to see larger patient numbers and more long-term data,” he said.
Dr. Reich had numerous disclosures, including honoraria for serving as a speaker for Eli Lilly, the sponsor of this trial.
AT AAD 2017
<p> </p><p><strong>Key clinical point: </strong><span class="tag metaDescription">Patients with moderate to severe plaque psoriasis can expect a better skin clearance response by 24 weeks with ixekizumab vs. ustekinumab.</span><br><br><strong>Major finding: </strong>At 24 weeks, ixekizumab was associated with significantly better PASI response rates and reduction in itch than ustekinumab in patients with moderate to severe plaque psoriasis.<br><br><strong>Data source: </strong>Head-to-head trial of 302 adults with moderate to severe plaque psoriasis treated with either ixekizumab or ustekinumab.<br><br><strong>Disclosures:</strong> Dr. Reich had numerous disclosures, including honoraria for serving as a speaker for Eli Lilly, the sponsor of this trial.</p>
Dupilumab improved eczema scores in children in open label trial
ORLANDO – Treatment with dupilumab in children and adolescents with moderate to severe atopic dermatitis (AD) reduced severity and pruritus scores from baseline and was well tolerated, in a multicenter, open-label trial of 78 children and adolescents.
Dupilumab’s “powerful ability” to block interleukin-4 and interleukin-13 pathways of inflammation is “especially exciting because AD is even more Th-2 cell driven in children,” said Michael J. Cork, MD, PhD, head of dermatologic research at the University of Sheffield (England), who presented the findings during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The study assessed the pharmacokinetics, safety, and efficacy of dupilumab and was conducted with 38 children, aged 6-11 years, and 40 adolescents, aged 12-17 years, with moderate to severe AD. All had failed topical corticosteroid therapy. Some of the children (16%) and adolescents (22.5%) had failed at least one systemic therapy.
Both age groups were given either a 2 mg/kg or a 4 mg/kg dose of dupilumab (administered subcutaneously), nothing for 8 weeks, followed by 4 weekly doses of their respective regimens. Mean Eczema Area and Severity Index (EASI) scores at baseline were 31.7 among the adolescents and 35.9 among the children.
At week 12, mean scores in the younger cohort given either 2 mg/kg or 4 mg/kg had improved by 76.2% and 63.4%, respectively, from baseline. In the adolescents, EASI scores at week 12 had improved by a mean of 66.4% in the 2-mg/kg group and 69.7% in the 4-mg/kg group.
Itch also improved “dramatically,” according to Dr. Cork. In the younger children, peak pruritus Numerical Rating Scale scores improved from baseline by a mean of 41.6% in the lower-dose group and 39.6% in the higher-dose group. In the older cohort, pruritus scores improved from baseline by a mean of 30.8% in the lower-dose group and 37.6% in the higher-dose group.
Treatment was well tolerated across the study, and adverse events were “mild, transient, and unrelated,” Dr. Cork said. “I would like to emphasize that these were not related to dupilumab, as they occurred during the period of time after the first dose, in weeks 6 and 7,” he commented. He attributed AD flares experienced in the study to the quick clearance of the drug in the first few weeks.
Dr. Cork reported numerous disclosures, including serving as an adviser, consultant, and investigator for Regeneron, the sponsor of the trial, and Sanofi; the companies developing dupilumab.
ORLANDO – Treatment with dupilumab in children and adolescents with moderate to severe atopic dermatitis (AD) reduced severity and pruritus scores from baseline and was well tolerated, in a multicenter, open-label trial of 78 children and adolescents.
Dupilumab’s “powerful ability” to block interleukin-4 and interleukin-13 pathways of inflammation is “especially exciting because AD is even more Th-2 cell driven in children,” said Michael J. Cork, MD, PhD, head of dermatologic research at the University of Sheffield (England), who presented the findings during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The study assessed the pharmacokinetics, safety, and efficacy of dupilumab and was conducted with 38 children, aged 6-11 years, and 40 adolescents, aged 12-17 years, with moderate to severe AD. All had failed topical corticosteroid therapy. Some of the children (16%) and adolescents (22.5%) had failed at least one systemic therapy.
Both age groups were given either a 2 mg/kg or a 4 mg/kg dose of dupilumab (administered subcutaneously), nothing for 8 weeks, followed by 4 weekly doses of their respective regimens. Mean Eczema Area and Severity Index (EASI) scores at baseline were 31.7 among the adolescents and 35.9 among the children.
At week 12, mean scores in the younger cohort given either 2 mg/kg or 4 mg/kg had improved by 76.2% and 63.4%, respectively, from baseline. In the adolescents, EASI scores at week 12 had improved by a mean of 66.4% in the 2-mg/kg group and 69.7% in the 4-mg/kg group.
Itch also improved “dramatically,” according to Dr. Cork. In the younger children, peak pruritus Numerical Rating Scale scores improved from baseline by a mean of 41.6% in the lower-dose group and 39.6% in the higher-dose group. In the older cohort, pruritus scores improved from baseline by a mean of 30.8% in the lower-dose group and 37.6% in the higher-dose group.
Treatment was well tolerated across the study, and adverse events were “mild, transient, and unrelated,” Dr. Cork said. “I would like to emphasize that these were not related to dupilumab, as they occurred during the period of time after the first dose, in weeks 6 and 7,” he commented. He attributed AD flares experienced in the study to the quick clearance of the drug in the first few weeks.
Dr. Cork reported numerous disclosures, including serving as an adviser, consultant, and investigator for Regeneron, the sponsor of the trial, and Sanofi; the companies developing dupilumab.
ORLANDO – Treatment with dupilumab in children and adolescents with moderate to severe atopic dermatitis (AD) reduced severity and pruritus scores from baseline and was well tolerated, in a multicenter, open-label trial of 78 children and adolescents.
Dupilumab’s “powerful ability” to block interleukin-4 and interleukin-13 pathways of inflammation is “especially exciting because AD is even more Th-2 cell driven in children,” said Michael J. Cork, MD, PhD, head of dermatologic research at the University of Sheffield (England), who presented the findings during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The study assessed the pharmacokinetics, safety, and efficacy of dupilumab and was conducted with 38 children, aged 6-11 years, and 40 adolescents, aged 12-17 years, with moderate to severe AD. All had failed topical corticosteroid therapy. Some of the children (16%) and adolescents (22.5%) had failed at least one systemic therapy.
Both age groups were given either a 2 mg/kg or a 4 mg/kg dose of dupilumab (administered subcutaneously), nothing for 8 weeks, followed by 4 weekly doses of their respective regimens. Mean Eczema Area and Severity Index (EASI) scores at baseline were 31.7 among the adolescents and 35.9 among the children.
At week 12, mean scores in the younger cohort given either 2 mg/kg or 4 mg/kg had improved by 76.2% and 63.4%, respectively, from baseline. In the adolescents, EASI scores at week 12 had improved by a mean of 66.4% in the 2-mg/kg group and 69.7% in the 4-mg/kg group.
Itch also improved “dramatically,” according to Dr. Cork. In the younger children, peak pruritus Numerical Rating Scale scores improved from baseline by a mean of 41.6% in the lower-dose group and 39.6% in the higher-dose group. In the older cohort, pruritus scores improved from baseline by a mean of 30.8% in the lower-dose group and 37.6% in the higher-dose group.
Treatment was well tolerated across the study, and adverse events were “mild, transient, and unrelated,” Dr. Cork said. “I would like to emphasize that these were not related to dupilumab, as they occurred during the period of time after the first dose, in weeks 6 and 7,” he commented. He attributed AD flares experienced in the study to the quick clearance of the drug in the first few weeks.
Dr. Cork reported numerous disclosures, including serving as an adviser, consultant, and investigator for Regeneron, the sponsor of the trial, and Sanofi; the companies developing dupilumab.
AT AAD 17
<p> </p><p><strong>Key clinical point: </strong>Data on dupilumab for treating moderate to severe atopic dermatitis in children and adolescents are promising.<br><br><strong>Major finding: </strong>At week 12, treatment with dupilumab at 2 mg/kg and 4 mg/kg doses, across 8 weeks in two pediatric cohorts improved baseline EASI scores by 69.7% and pruritus scores by a third and was well tolerated.<br><br><strong>Data source: </strong>A phase IIa, multicenter, open label pharmacokinetics, safety, and efficacy trial evaluating two dosing regimens of dupilumab in 78 children with moderate to severe AD.<br><br><strong>Disclosures: </strong>Dr. Cork reported numerous disclosures, including serving as an adviser, consultant, and investigator for Regeneron, the sponsor of the trial, and Sanofi – the two companies developing dupilumab.</p>
Are new medications on horizon for patients with depression, inflammation?
SCOTTSDALE, ARIZ. – Inflammation is inextricably linked to depression in a subset of patients who differ from other depressed patients in their responses to certain interventions, according to Charles L. Raison, MD.
“The brains of people who are depressed and who have inflammation look very different from those of people who are depressed without inflammation,” Dr. Raison said in an interview at the annual meeting of the American College of Psychiatrists. “They have different connectivity patterns, different glutaminergic patterns, different signaling. It seems that inflammatory processes change the way different parts of the brain talk to each other and seem to do so in consistent ways.”
Dr. Raison, the Mary Sue and Mike Shannon Chair for Healthy Minds, Children & Families at the University of Wisconsin–Madison, told a plenary audience at the meeting: “We [psychiatrists] are so brain centric, it’s easy to forget how much the immune system drives us. It’s either like a second brain, or it is at least part of the brain.” 
Over the years, Dr. Raison and his colleagues have observed how inflammation can interfere with mood, leading to depression in people who previously did not report or describe depressive symptoms.
In the early 2000s, Dr. Raison and others such as Andrew H. Miller, MD, a psychiatric oncologist, investigated the inflammatory response and levels of depression in people treated with interferon-alpha for hepatitis C infection (J Clin Psychiatry. 2005 Jan;66[1]:41-8). They found that more than half of people who had not reported or described depressive symptoms at baseline subsequently reported depressive symptoms. “In a nutshell, we found that interferon-alpha induces every single brain-body function associated with regular old major depression,” said Dr. Raison, also a professor of psychiatry at the university.
In another study, this one led by neuropsychosomatic specialist Dominique L. Musselman, MD, a similar cohort of hepatitis C patients assessed for baseline depression was randomly assigned to either placebo or paroxetine during the course of interferon-alpha treatment. Patients treated with placebo had a 0.24 relative risk (95% confidence interval, 0.08-0.93) of developing depression, compared with the paroxetine group (N Eng J Med. 2001;344:961-6).
The real “breakthrough” in understanding the role of inflammation in depression, Dr. Raison said, came from studies that made the association between early-life adversity, depression, and inflammation. In one particular study, Dr. Raison and colleagues found that stress-induced spikes in interleukin-6 and NF-kappaB DNA-binding were greater in patients with higher baseline levels of depression and higher levels of early life stress (Am J Psychiatry. 2006 Sep;163[9]:1630-3).
Spikes in the inflammatory response independently correlated with depression severity but not with early life stress, which Dr. Raison said suggests that adversity likely can cause inflammation – and thus predisposes people to depression, and not necessarily vice versa.
“Something about early adversity in life programs the brain-body complex to run inflammatory systems hot, probably because it’s an effective way to be ready for [a stream of] unpredictable miseries,” Dr. Raison said during the session. “Chronic, elevated inflammation [early on] seems to predict increased depression later.”
Now that the link has been established between some depression and inflammation, the next step for science is to tease out who is most likely to respond to anti-inflammatory interventions for depression, Dr. Raison said.
“Something that is just starting to emerge is that maybe the relationship between inflammation and depression is not a straight line but a U-shaped curve, such that if you have too much inflammation, you’re in trouble, and if you have too little, you’re also in trouble,” he said in the interview, citing a study he and others conducted into blocking the inflammatory response. In that study, people with major depression who were otherwise medically healthy received either three infusions of the anti-inflammatory tumor necrosis factor–alpha antagonist infliximab (5 mg/kg), or of salt water. The investigators found that placebo worked just as well as infliximab. But patients with lower levels of inflammation at baseline had the greatest improvements in their Hamilton Rating Scale for Depression scores with placebo when compared with treatment (JAMA Psychiatry. 2013 Jan;70[1]:31-41).
Data are not yet conclusive, but Dr. Raison said the field soon could use biomarkers such as levels of C-reactive protein to determine whether patients will respond to anti-inflammatories such as omega-3 essential fatty acids. “Everyone in psychiatry is desperate to find clear, unambiguous answers. We’re right on the edge, but we’re not there yet.”
Until then, Dr. Raison cautioned against the “indiscriminate” use of anti-inflammatories, lest they exacerbate patients’ depressive symptoms. “For instance, omega-3 fatty acids might actually be counterproductive in a lot of depressed people,” he said. Still, he believes that “developing and studying anti-inflammatory strategies is probably going to lead to a novel way of treating depression in some people. What is beautiful is that if these studies continue, we might actually be able – for the first time – to target a subgroup of patients for a specific treatment.”
Dr. Raison is on the scientific advisory board of the Usona Institute, a nonprofit medical research firm.
SCOTTSDALE, ARIZ. – Inflammation is inextricably linked to depression in a subset of patients who differ from other depressed patients in their responses to certain interventions, according to Charles L. Raison, MD.
“The brains of people who are depressed and who have inflammation look very different from those of people who are depressed without inflammation,” Dr. Raison said in an interview at the annual meeting of the American College of Psychiatrists. “They have different connectivity patterns, different glutaminergic patterns, different signaling. It seems that inflammatory processes change the way different parts of the brain talk to each other and seem to do so in consistent ways.”
Dr. Raison, the Mary Sue and Mike Shannon Chair for Healthy Minds, Children & Families at the University of Wisconsin–Madison, told a plenary audience at the meeting: “We [psychiatrists] are so brain centric, it’s easy to forget how much the immune system drives us. It’s either like a second brain, or it is at least part of the brain.”
Over the years, Dr. Raison and his colleagues have observed how inflammation can interfere with mood, leading to depression in people who previously did not report or describe depressive symptoms.
In the early 2000s, Dr. Raison and others such as Andrew H. Miller, MD, a psychiatric oncologist, investigated the inflammatory response and levels of depression in people treated with interferon-alpha for hepatitis C infection (J Clin Psychiatry. 2005 Jan;66[1]:41-8). They found that more than half of people who had not reported or described depressive symptoms at baseline subsequently reported depressive symptoms. “In a nutshell, we found that interferon-alpha induces every single brain-body function associated with regular old major depression,” said Dr. Raison, also a professor of psychiatry at the university.
In another study, this one led by neuropsychosomatic specialist Dominique L. Musselman, MD, a similar cohort of hepatitis C patients assessed for baseline depression was randomly assigned to either placebo or paroxetine during the course of interferon-alpha treatment. Patients treated with placebo had a 0.24 relative risk (95% confidence interval, 0.08-0.93) of developing depression, compared with the paroxetine group (N Eng J Med. 2001;344:961-6).
The real “breakthrough” in understanding the role of inflammation in depression, Dr. Raison said, came from studies that made the association between early-life adversity, depression, and inflammation. In one particular study, Dr. Raison and colleagues found that stress-induced spikes in interleukin-6 and NF-kappaB DNA-binding were greater in patients with higher baseline levels of depression and higher levels of early life stress (Am J Psychiatry. 2006 Sep;163[9]:1630-3).
Spikes in the inflammatory response independently correlated with depression severity but not with early life stress, which Dr. Raison said suggests that adversity likely can cause inflammation – and thus predisposes people to depression, and not necessarily vice versa.
“Something about early adversity in life programs the brain-body complex to run inflammatory systems hot, probably because it’s an effective way to be ready for [a stream of] unpredictable miseries,” Dr. Raison said during the session. “Chronic, elevated inflammation [early on] seems to predict increased depression later.”
Now that the link has been established between some depression and inflammation, the next step for science is to tease out who is most likely to respond to anti-inflammatory interventions for depression, Dr. Raison said.
“Something that is just starting to emerge is that maybe the relationship between inflammation and depression is not a straight line but a U-shaped curve, such that if you have too much inflammation, you’re in trouble, and if you have too little, you’re also in trouble,” he said in the interview, citing a study he and others conducted into blocking the inflammatory response. In that study, people with major depression who were otherwise medically healthy received either three infusions of the anti-inflammatory tumor necrosis factor–alpha antagonist infliximab (5 mg/kg), or of salt water. The investigators found that placebo worked just as well as infliximab. But patients with lower levels of inflammation at baseline had the greatest improvements in their Hamilton Rating Scale for Depression scores with placebo when compared with treatment (JAMA Psychiatry. 2013 Jan;70[1]:31-41).
Data are not yet conclusive, but Dr. Raison said the field soon could use biomarkers such as levels of C-reactive protein to determine whether patients will respond to anti-inflammatories such as omega-3 essential fatty acids. “Everyone in psychiatry is desperate to find clear, unambiguous answers. We’re right on the edge, but we’re not there yet.”
Until then, Dr. Raison cautioned against the “indiscriminate” use of anti-inflammatories, lest they exacerbate patients’ depressive symptoms. “For instance, omega-3 fatty acids might actually be counterproductive in a lot of depressed people,” he said. Still, he believes that “developing and studying anti-inflammatory strategies is probably going to lead to a novel way of treating depression in some people. What is beautiful is that if these studies continue, we might actually be able – for the first time – to target a subgroup of patients for a specific treatment.”
Dr. Raison is on the scientific advisory board of the Usona Institute, a nonprofit medical research firm.
SCOTTSDALE, ARIZ. – Inflammation is inextricably linked to depression in a subset of patients who differ from other depressed patients in their responses to certain interventions, according to Charles L. Raison, MD.
“The brains of people who are depressed and who have inflammation look very different from those of people who are depressed without inflammation,” Dr. Raison said in an interview at the annual meeting of the American College of Psychiatrists. “They have different connectivity patterns, different glutaminergic patterns, different signaling. It seems that inflammatory processes change the way different parts of the brain talk to each other and seem to do so in consistent ways.”
Dr. Raison, the Mary Sue and Mike Shannon Chair for Healthy Minds, Children & Families at the University of Wisconsin–Madison, told a plenary audience at the meeting: “We [psychiatrists] are so brain centric, it’s easy to forget how much the immune system drives us. It’s either like a second brain, or it is at least part of the brain.”
Over the years, Dr. Raison and his colleagues have observed how inflammation can interfere with mood, leading to depression in people who previously did not report or describe depressive symptoms.
In the early 2000s, Dr. Raison and others such as Andrew H. Miller, MD, a psychiatric oncologist, investigated the inflammatory response and levels of depression in people treated with interferon-alpha for hepatitis C infection (J Clin Psychiatry. 2005 Jan;66[1]:41-8). They found that more than half of people who had not reported or described depressive symptoms at baseline subsequently reported depressive symptoms. “In a nutshell, we found that interferon-alpha induces every single brain-body function associated with regular old major depression,” said Dr. Raison, also a professor of psychiatry at the university.
In another study, this one led by neuropsychosomatic specialist Dominique L. Musselman, MD, a similar cohort of hepatitis C patients assessed for baseline depression was randomly assigned to either placebo or paroxetine during the course of interferon-alpha treatment. Patients treated with placebo had a 0.24 relative risk (95% confidence interval, 0.08-0.93) of developing depression, compared with the paroxetine group (N Eng J Med. 2001;344:961-6).
The real “breakthrough” in understanding the role of inflammation in depression, Dr. Raison said, came from studies that made the association between early-life adversity, depression, and inflammation. In one particular study, Dr. Raison and colleagues found that stress-induced spikes in interleukin-6 and NF-kappaB DNA-binding were greater in patients with higher baseline levels of depression and higher levels of early life stress (Am J Psychiatry. 2006 Sep;163[9]:1630-3).
Spikes in the inflammatory response independently correlated with depression severity but not with early life stress, which Dr. Raison said suggests that adversity likely can cause inflammation – and thus predisposes people to depression, and not necessarily vice versa.
“Something about early adversity in life programs the brain-body complex to run inflammatory systems hot, probably because it’s an effective way to be ready for [a stream of] unpredictable miseries,” Dr. Raison said during the session. “Chronic, elevated inflammation [early on] seems to predict increased depression later.”
Now that the link has been established between some depression and inflammation, the next step for science is to tease out who is most likely to respond to anti-inflammatory interventions for depression, Dr. Raison said.
“Something that is just starting to emerge is that maybe the relationship between inflammation and depression is not a straight line but a U-shaped curve, such that if you have too much inflammation, you’re in trouble, and if you have too little, you’re also in trouble,” he said in the interview, citing a study he and others conducted into blocking the inflammatory response. In that study, people with major depression who were otherwise medically healthy received either three infusions of the anti-inflammatory tumor necrosis factor–alpha antagonist infliximab (5 mg/kg), or of salt water. The investigators found that placebo worked just as well as infliximab. But patients with lower levels of inflammation at baseline had the greatest improvements in their Hamilton Rating Scale for Depression scores with placebo when compared with treatment (JAMA Psychiatry. 2013 Jan;70[1]:31-41).
Data are not yet conclusive, but Dr. Raison said the field soon could use biomarkers such as levels of C-reactive protein to determine whether patients will respond to anti-inflammatories such as omega-3 essential fatty acids. “Everyone in psychiatry is desperate to find clear, unambiguous answers. We’re right on the edge, but we’re not there yet.”
Until then, Dr. Raison cautioned against the “indiscriminate” use of anti-inflammatories, lest they exacerbate patients’ depressive symptoms. “For instance, omega-3 fatty acids might actually be counterproductive in a lot of depressed people,” he said. Still, he believes that “developing and studying anti-inflammatory strategies is probably going to lead to a novel way of treating depression in some people. What is beautiful is that if these studies continue, we might actually be able – for the first time – to target a subgroup of patients for a specific treatment.”
Dr. Raison is on the scientific advisory board of the Usona Institute, a nonprofit medical research firm.
EXPERT OPINION FROM THE AMERICAN COLLEGE OF PSYCHIATRISTS MEETING
Adalimumab for psoriasis: Blocking TNF-alpha had no effect on vascular inflammation
ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.
Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.
At 16 weeks, there were no significant differences in vascular inflammation between the treatment and control arms, based on the change from baseline in the vessel wall target to background ratio from the ascending aorta (the primary endpoint). In the carotid arteries at 16 weeks, differences in vascular inflammation between the adalimumab group and control group were also not significant.
At 52 weeks, there was no significant change in target to background ratio from the ascending aorta between baseline and the start of adalimumab, although in the carotid arteries, there was a modest increase in vascular inflammation.
Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”
Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.
Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).
Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.
In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).
Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.
Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.
Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.
At 16 weeks, there were no significant differences in vascular inflammation between the treatment and control arms, based on the change from baseline in the vessel wall target to background ratio from the ascending aorta (the primary endpoint). In the carotid arteries at 16 weeks, differences in vascular inflammation between the adalimumab group and control group were also not significant.
At 52 weeks, there was no significant change in target to background ratio from the ascending aorta between baseline and the start of adalimumab, although in the carotid arteries, there was a modest increase in vascular inflammation.
Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”
Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.
Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).
Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.
In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).
Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.
Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.
Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.
At 16 weeks, there were no significant differences in vascular inflammation between the treatment and control arms, based on the change from baseline in the vessel wall target to background ratio from the ascending aorta (the primary endpoint). In the carotid arteries at 16 weeks, differences in vascular inflammation between the adalimumab group and control group were also not significant.
At 52 weeks, there was no significant change in target to background ratio from the ascending aorta between baseline and the start of adalimumab, although in the carotid arteries, there was a modest increase in vascular inflammation.
Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”
Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.
Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).
Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.
In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).
Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.
Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
<p> </p><p><strong>Key clinical point: </strong><span class="tag metaDescription">Treatment with a tumor necrosis factor alpha-antagonist may not reduce vascular inflammation.</span><br><br><strong>Major finding: </strong>At 16 weeks, there were no significant differences in aortic and carotid inflammation in the change from baseline in moderate psoriasis patients given adalimumab and controls.<br><br><strong>Data source: </strong>A randomized, double-blind multicenter study that used PET-CT scans to evaluate the impact of treatment on vascular inflammation in 107 adults with moderate to severe psoriasis.<br><br><strong>Disclosures:</strong> Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.<br> </p>
VIDEO: Stress alleviation strategies boost inflammatory skin treatment regimens
ORLANDO – “Consider the effects of the mind on the skin when treating patients with some skin diseases.” That was the message of several speakers during a session titled “The Skin and the Mind” at the annual meeting of the American Academy of Dermatology.
“I certainly believe that the time has come to use stress alleviation techniques, at least for selected patients, and this should certainly be part of our armamentarium in the clinic,” said Richard D. Granstein, MD, George W. Hambrick Jr. professor and chairman of the department of dermatology, Cornell University, New York. During the session, he spoke about the emerging science of stress in dermatology.
While it has long been believed that stress exacerbates different skin diseases, the connection has been difficult to prove scientifically, he pointed out. However, “the overwhelming number of reports and studies indicate that stress probably does exacerbate a number of inflammatory skin diseases,” he added.
In a video interview at the meeting, Dr. Granstein notes that a number of pathways that help explain this link have now been identified and discusses one of those pathways, which involves neuropeptides and future directions in understanding the relationship between stress and inflammatory skin diseases.
Dr. Granstein disclosed serving as an advisor to Castle Biosciences, Elysium Health, Galderma Laboratories, and Velius.
ORLANDO – “Consider the effects of the mind on the skin when treating patients with some skin diseases.” That was the message of several speakers during a session titled “The Skin and the Mind” at the annual meeting of the American Academy of Dermatology.
“I certainly believe that the time has come to use stress alleviation techniques, at least for selected patients, and this should certainly be part of our armamentarium in the clinic,” said Richard D. Granstein, MD, George W. Hambrick Jr. professor and chairman of the department of dermatology, Cornell University, New York. During the session, he spoke about the emerging science of stress in dermatology.
While it has long been believed that stress exacerbates different skin diseases, the connection has been difficult to prove scientifically, he pointed out. However, “the overwhelming number of reports and studies indicate that stress probably does exacerbate a number of inflammatory skin diseases,” he added.
In a video interview at the meeting, Dr. Granstein notes that a number of pathways that help explain this link have now been identified and discusses one of those pathways, which involves neuropeptides and future directions in understanding the relationship between stress and inflammatory skin diseases.
Dr. Granstein disclosed serving as an advisor to Castle Biosciences, Elysium Health, Galderma Laboratories, and Velius.
ORLANDO – “Consider the effects of the mind on the skin when treating patients with some skin diseases.” That was the message of several speakers during a session titled “The Skin and the Mind” at the annual meeting of the American Academy of Dermatology.
“I certainly believe that the time has come to use stress alleviation techniques, at least for selected patients, and this should certainly be part of our armamentarium in the clinic,” said Richard D. Granstein, MD, George W. Hambrick Jr. professor and chairman of the department of dermatology, Cornell University, New York. During the session, he spoke about the emerging science of stress in dermatology.
While it has long been believed that stress exacerbates different skin diseases, the connection has been difficult to prove scientifically, he pointed out. However, “the overwhelming number of reports and studies indicate that stress probably does exacerbate a number of inflammatory skin diseases,” he added.
In a video interview at the meeting, Dr. Granstein notes that a number of pathways that help explain this link have now been identified and discusses one of those pathways, which involves neuropeptides and future directions in understanding the relationship between stress and inflammatory skin diseases.
Dr. Granstein disclosed serving as an advisor to Castle Biosciences, Elysium Health, Galderma Laboratories, and Velius.
AT AAD 17
VIDEO: Consider alopecia ‘camouflage kits’ to boost patients’ self-esteem
ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.
Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.
“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.
Dr. Schmidt had no relevant disclosures.
ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.
Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.
“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.
Dr. Schmidt had no relevant disclosures.
ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.
Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.
“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.
Dr. Schmidt had no relevant disclosures.
AT AAD 2017
New 52-week EASI, pruritus data strengthen case for dupilumab in adult atopic dermatitis
ORLANDO – Treatment with dupilumab was associated with significantly improved measures of disease severity, including in quality of life and pruritus symptoms, at 16 and 52 weeks in adults with moderate to severe atopic dermatitis (AD) in the phase III CHRONOS trial.
In the CHRONOS study of adults with uncontrolled, moderate to severe AD, patients were treated with the investigational biologic dupilumab (Dupixent), an interleukin-4 and interleukin-13 pathway blocker administered in subcutaneous injections, in combination with topical corticosteroids. At 52 weeks, they had achieved significantly improved measures of overall disease severity, compared with those who received corticosteroids alone, according to Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, who presented the new data from the study in a late-breaking clinical session at the annual meeting of the American Academy of Dermatology.
The new 52-week data presented at AAD show that the mean improvement in the EASI score from baseline was 80% in the 300 mg dupilumab every week plus corticosteroid group (group 1) and 78% in the group treated every 2 weeks (group 2), compared with 46% in the placebo plus corticosteroids group (control) (P less than .0001).
The mean improvement in self-reported itch from baseline, as measured by the Pruritus Numerical Rating Scale, was 54% in the first group, 56% in the second group, compared with 27% in controls (P less than .0001).
In the first group, 65% achieved a 4-point or greater improvement in their Patient Oriented Eczema Measure scores, as did 76% of the second group, compared with 26% of controls (P less than .0001).
At least a 4-point improvement over baseline in Dermatology Life Quality Index scores was seen in 63% of group 1, 80% of group 2, and 30% of controls (P less than .0001).
Adverse events across the study were similar, although the treatment groups had higher incidences of injection site reactions: 19% in group 1 and 15% in group 2, compared with 8% in controls. The treatment groups also had higher rates of conjunctivitis: 19% in group 1 and 14% in group 2, compared with 8% in controls.
Dr. Blauvelt said that patients who were “exited from the trial were continued for follow-up” and that rescue therapies such as cyclosporine, and other systemic agents, were also available. The rate of rescue therapy was about 15% in the first two groups, while half of controls needed rescue therapy. “We considered those patients who needed rescue nonresponders,” he noted.
The dropout rate at week 52 was about 15% across the treatment groups, compared with twice that in controls.
“Atopic dermatitis is the new psoriasis. We’re in an exciting area now, and we’ll be seeing more biologic therapies for moderate to severe atopic dermatitis. We have a tremendous need for this,” Dr. Blauvelt commented.
The Food and Drug Administration is expected to make a decision on approval of dupilumab by March 29, 2017. Dupilumab was designated by the FDA as a breakthrough therapy for uncontrolled, moderate to severe AD in 2014.
Dr. Blauvelt disclosed many pharmaceutical industry relationships, including with Regeneron Pharmaceuticals and Sanofi, which are developing dupilumab. (If approved, Regeneron and Sanofi Genzyme, part of Sanofi, will commercialize dupilumab).
CORRECTION 3/10/17: An earlier version of this article misstated the rates of clear or nearly clear skin.
ORLANDO – Treatment with dupilumab was associated with significantly improved measures of disease severity, including in quality of life and pruritus symptoms, at 16 and 52 weeks in adults with moderate to severe atopic dermatitis (AD) in the phase III CHRONOS trial.
In the CHRONOS study of adults with uncontrolled, moderate to severe AD, patients were treated with the investigational biologic dupilumab (Dupixent), an interleukin-4 and interleukin-13 pathway blocker administered in subcutaneous injections, in combination with topical corticosteroids. At 52 weeks, they had achieved significantly improved measures of overall disease severity, compared with those who received corticosteroids alone, according to Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, who presented the new data from the study in a late-breaking clinical session at the annual meeting of the American Academy of Dermatology.
The new 52-week data presented at AAD show that the mean improvement in the EASI score from baseline was 80% in the 300 mg dupilumab every week plus corticosteroid group (group 1) and 78% in the group treated every 2 weeks (group 2), compared with 46% in the placebo plus corticosteroids group (control) (P less than .0001).
The mean improvement in self-reported itch from baseline, as measured by the Pruritus Numerical Rating Scale, was 54% in the first group, 56% in the second group, compared with 27% in controls (P less than .0001).
In the first group, 65% achieved a 4-point or greater improvement in their Patient Oriented Eczema Measure scores, as did 76% of the second group, compared with 26% of controls (P less than .0001).
At least a 4-point improvement over baseline in Dermatology Life Quality Index scores was seen in 63% of group 1, 80% of group 2, and 30% of controls (P less than .0001).
Adverse events across the study were similar, although the treatment groups had higher incidences of injection site reactions: 19% in group 1 and 15% in group 2, compared with 8% in controls. The treatment groups also had higher rates of conjunctivitis: 19% in group 1 and 14% in group 2, compared with 8% in controls.
Dr. Blauvelt said that patients who were “exited from the trial were continued for follow-up” and that rescue therapies such as cyclosporine, and other systemic agents, were also available. The rate of rescue therapy was about 15% in the first two groups, while half of controls needed rescue therapy. “We considered those patients who needed rescue nonresponders,” he noted.
The dropout rate at week 52 was about 15% across the treatment groups, compared with twice that in controls.
“Atopic dermatitis is the new psoriasis. We’re in an exciting area now, and we’ll be seeing more biologic therapies for moderate to severe atopic dermatitis. We have a tremendous need for this,” Dr. Blauvelt commented.
The Food and Drug Administration is expected to make a decision on approval of dupilumab by March 29, 2017. Dupilumab was designated by the FDA as a breakthrough therapy for uncontrolled, moderate to severe AD in 2014.
Dr. Blauvelt disclosed many pharmaceutical industry relationships, including with Regeneron Pharmaceuticals and Sanofi, which are developing dupilumab. (If approved, Regeneron and Sanofi Genzyme, part of Sanofi, will commercialize dupilumab).
CORRECTION 3/10/17: An earlier version of this article misstated the rates of clear or nearly clear skin.
ORLANDO – Treatment with dupilumab was associated with significantly improved measures of disease severity, including in quality of life and pruritus symptoms, at 16 and 52 weeks in adults with moderate to severe atopic dermatitis (AD) in the phase III CHRONOS trial.
In the CHRONOS study of adults with uncontrolled, moderate to severe AD, patients were treated with the investigational biologic dupilumab (Dupixent), an interleukin-4 and interleukin-13 pathway blocker administered in subcutaneous injections, in combination with topical corticosteroids. At 52 weeks, they had achieved significantly improved measures of overall disease severity, compared with those who received corticosteroids alone, according to Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, who presented the new data from the study in a late-breaking clinical session at the annual meeting of the American Academy of Dermatology.
The new 52-week data presented at AAD show that the mean improvement in the EASI score from baseline was 80% in the 300 mg dupilumab every week plus corticosteroid group (group 1) and 78% in the group treated every 2 weeks (group 2), compared with 46% in the placebo plus corticosteroids group (control) (P less than .0001).
The mean improvement in self-reported itch from baseline, as measured by the Pruritus Numerical Rating Scale, was 54% in the first group, 56% in the second group, compared with 27% in controls (P less than .0001).
In the first group, 65% achieved a 4-point or greater improvement in their Patient Oriented Eczema Measure scores, as did 76% of the second group, compared with 26% of controls (P less than .0001).
At least a 4-point improvement over baseline in Dermatology Life Quality Index scores was seen in 63% of group 1, 80% of group 2, and 30% of controls (P less than .0001).
Adverse events across the study were similar, although the treatment groups had higher incidences of injection site reactions: 19% in group 1 and 15% in group 2, compared with 8% in controls. The treatment groups also had higher rates of conjunctivitis: 19% in group 1 and 14% in group 2, compared with 8% in controls.
Dr. Blauvelt said that patients who were “exited from the trial were continued for follow-up” and that rescue therapies such as cyclosporine, and other systemic agents, were also available. The rate of rescue therapy was about 15% in the first two groups, while half of controls needed rescue therapy. “We considered those patients who needed rescue nonresponders,” he noted.
The dropout rate at week 52 was about 15% across the treatment groups, compared with twice that in controls.
“Atopic dermatitis is the new psoriasis. We’re in an exciting area now, and we’ll be seeing more biologic therapies for moderate to severe atopic dermatitis. We have a tremendous need for this,” Dr. Blauvelt commented.
The Food and Drug Administration is expected to make a decision on approval of dupilumab by March 29, 2017. Dupilumab was designated by the FDA as a breakthrough therapy for uncontrolled, moderate to severe AD in 2014.
Dr. Blauvelt disclosed many pharmaceutical industry relationships, including with Regeneron Pharmaceuticals and Sanofi, which are developing dupilumab. (If approved, Regeneron and Sanofi Genzyme, part of Sanofi, will commercialize dupilumab).
CORRECTION 3/10/17: An earlier version of this article misstated the rates of clear or nearly clear skin.
AT AAD 2017
<p> </p><p><strong>Key clinical point: </strong><span class="tag metaDescription">Treatment with the interleukin-4 and -13 inhibitor dupilumab results in significant clearing and reduced itching of disease, as well as reduces severity of disease, in patients with moderate to severe AD.</span><br><br><strong>Major finding:</strong> At 52 weeks, dupilumab 300 mg administered in a subcutaneous injection once a week or every two weeks plus topical corticosteroids resulted in significantly more clearing compared with topical corticosteroids alone (<em>P</em> less than .0001). Self-reported measures of itch and quality-of-life measures were also higher across treatment groups.<br><br><strong>Data source: </strong>A phase III trial of 740 adults with moderate to severe AD, randomized to treatment with one of the two regimens or corticosteroids alone.<br><br><strong>Disclosures:</strong> Dr. Blauvelt disclosed many pharmaceutical industry relationships, including with Regeneron Pharmaceuticals and Sanofi, which are developing dupilumab. (If approved, Regeneron and Sanofi Genzyme, part of Sanofi, will commercialize dupilumab).</p>
VIDEO: Tips, tricks, and pearls for keloid scar steroid injections
ORLANDO – What are the best ways to avoid atrophy when treating keloid scars with steroid injections? When should a keloid be treated with smaller amounts, but with a stronger steroid concentration? What is the most effective way to avoid precipitation in the syringe?
The answers to these questions – along with other tips, tricks, and pearls for treating keloids, both in patients with skin of color and those with white skin – are provided by Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, in a video interview at the annual meeting of the American Academy of Dermatology.
Dr. Ogunleye had no relevant disclosures.
ORLANDO – What are the best ways to avoid atrophy when treating keloid scars with steroid injections? When should a keloid be treated with smaller amounts, but with a stronger steroid concentration? What is the most effective way to avoid precipitation in the syringe?
The answers to these questions – along with other tips, tricks, and pearls for treating keloids, both in patients with skin of color and those with white skin – are provided by Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, in a video interview at the annual meeting of the American Academy of Dermatology.
Dr. Ogunleye had no relevant disclosures.
ORLANDO – What are the best ways to avoid atrophy when treating keloid scars with steroid injections? When should a keloid be treated with smaller amounts, but with a stronger steroid concentration? What is the most effective way to avoid precipitation in the syringe?
The answers to these questions – along with other tips, tricks, and pearls for treating keloids, both in patients with skin of color and those with white skin – are provided by Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, in a video interview at the annual meeting of the American Academy of Dermatology.
Dr. Ogunleye had no relevant disclosures.
AT AAD 17
VIDEO: Working with alopecia patients’ insurers when using novel therapies
ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.
In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”
In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.
She had no disclosures.
ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.
In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”
In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.
She had no disclosures.
ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.
In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”
In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.
She had no disclosures.
AT AAD 17
VIDEO: Grading tools help set alopecia treatment expectations and monitor progress
ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.
The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.
He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.
Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.
ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.
The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.
He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.
Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.
ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.
The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.
He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.
Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.
AT AAD 17
