Psoriasis

Psoriasis is a chronic inflammatory skin disorder that affects patients’ quality of life and social interactions.¹ Several studies have shown a strong consistent association between psoriasis and depression as well as possible suicidal ideation and behavior (SIB).^1-13 Notable findings from a 2018 review found depression prevalence ranged from 2.1% to 33.7% among patients with psoriasis vs 0% to 22.7% among unaffected patients.⁷ In a 2017 meta-analysis, Singh et al² found increased odds of SIB (odds ratio [OR], 2.05), attempted suicide (OR, 1.32), and completed suicide (OR, 1.20) in patients with psoriasis compared to those without psoriasis. In 2018, Wu and colleagues⁷ reported that odds of SIB among patients with psoriasis ranged from 1.01 to 1.94 times those of patients without psoriasis, and SIB and suicide attempts were more common than in patients with other dermatologic conditions. Koo and colleagues¹ reached similar conclusions. At the same time, the occurrence of attempted and completed suicides among patients in psoriasis clinical trials has raised concerns about whether psoriasis medications also may increase the risk for SIB.⁷

We review research on the effects of psoriasis treatment on patients’ symptoms of depression and SIB, with a focus on recent analyses of depressive symptoms and SIB among patients with psoriasis who received brodalumab in clinical trials. Finally, we suggest approaches clinicians may consider when caring for patients with psoriasis who may be at risk for depression and SIB.

MATERIALS AND METHODS

We reviewed research on the effects of biologic therapy for psoriasis on depression and SIB, with a primary focus on recent large meta-analyses. Published findings on the pattern of SIB in brodalumab clinical trials and effects of brodalumab treatment on symptoms of depression and anxiety are summarized. The most recent evidence (January 2014–December 2018) regarding the mental health comorbidities of psoriasis was assessed using published English-language research data and review articles according to a PubMed search of articles indexed for MEDLINE using the following terms: depression, anxiety, suicide, suicidal ideation and behavior, SIB, brodalumab, or psoriasis. We also reviewed citations within articles to identify relevant sources. Implications for clinical care of patients with psoriasis are discussed based on expert recommendations and the authors’ clinical experience.

RESULTS

Effects of Psoriasis Treatment on Symptoms of Depression and Suicidality

Occurrences of attempted suicide and completed suicide have been reported during treatment with several psoriasis medications,^7,9 raising concerns about whether these medications increase the risk for depression and SIB in an already vulnerable population. Wu and colleagues⁷ reviewed 11 studies published from 2006 to 2017 reporting the effects of medications for the treatment of psoriasis—adalimumab, apremilast, brodalumab, etanercept, and ustekinumab—on measures of depression and anxiety such as the Beck Depression Inventory, the Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire (PHQ) 8. In each of the 11 studies, symptoms of depression improved after treatment, over time, or compared to placebo. Notably, the magnitude of improvement in symptoms of depression was not strongly linked to the magnitude of clinical improvement.⁷ Other recent studies have reported reductions in symptoms of depression with biologic therapies, including adalimumab, etanercept, guselkumab, ixekizumab, secukinumab, and ustekinumab.^14-21

With respect to suicidality, an analysis of publicly available data found low rates of completed and attempted suicides (point estimates of 0.0–0.15 per 100 patient-years) in clinical development programs of apremilast, brodalumab, ixekizumab, and secukinumab. Patient suicidality in these trials often occurred in the context of risk factors or stressors such as work, financial difficulties, depression, and substance abuse.⁷ In a detailed 2016 analysis of suicidal behaviors during clinical trials of apremilast, brodalumab, etanercept, infliximab, ixekizumab, secukinumab, tofacitinib, ustekinumab, and other investigational agents, Gooderham and colleagues⁹ concluded that the behaviors may have resulted from the disease or patients’ psychosocial status rather than from treatment and that treatment with biologics does not increase the risk for SIB. Improvements in symptoms of depression during treatment suggest the potential to improve patients’ psychiatric outcomes with biologic treatment.⁹

Evidence From Brodalumab Studies

Intensive efforts have been made to assess the effect of brodalumab, a fully human anti–IL-17RA monoclonal antibody shown to be efficacious in the treatment of moderate to severe plaque psoriasis, on symptoms of depression and to understand the incidence of SIB among patients receiving brodalumab in clinical trials.^22-27

Depression and Anxiety in Studies of Brodalumab
To examine the effects of brodalumab on symptoms of depression, the HADS questionnaire²⁸ was administered to patients in 1 of 3 phase 3 clinical trials of brodalumab.²³ A HADS score of 0 to 7 is considered normal, 8 to 10 is mild, 11 to 14 is moderate, and 15 to 21 is severe.²³ The HADS questionnaire was administered to evaluate the presence and severity of depression and anxiety symptoms at baseline and at weeks 12, 24, 36, and 52.²⁵ This scale was not used in the other 2 phase 3 studies of brodalumab because at the time those studies were initiated, there was no indication to include mental health screenings as part of the study protocol.

Patients were initially randomized to placebo (n=220), brodalumab 140 mg every 2 weeks (Q2W; n=219), or brodalumab 210 mg Q2W (the eventual approved dose; n=222) for 12 weeks.²³ At week 12, patients initially randomized to placebo were switched to brodalumab through week 52. Patients initially randomized to brodalumab 210 mg Q2W were re-randomized to either placebo or brodalumab 210 mg Q2W.²³ Depression and anxiety were common at baseline. Based on HADS scores, depression occurred among 27% and 26% of patients randomized to brodalumab and placebo, respectively; anxiety occurred in 36% of patients in each group.²² Among patients receiving brodalumab 210 mg Q2W from baseline to week 12, HADS depression scores improved in 67% of patients and worsened in 19%. In contrast, the proportion of patients receiving placebo whose depression scores improved (45%) was similar to the proportion whose scores worsened (38%). Hospital Anxiety and Depression Scale anxiety scores also improved more often with brodalumab than with placebo.²²

Furthermore, among patients who had moderate or severe depression or anxiety at baseline, a greater percentage experienced improvement with brodalumab than placebo.²³ Among 30 patients with moderate to severe HADS depression scores at baseline who were treated with brodalumab 210 mg Q2W, 22 (73%) improved by at least 1 depression category by week 12; in the placebo group, 10 of 22 (45%) improved. Among patients with moderate or severe anxiety scores, 28 of 42 patients (67%) treated with brodalumab 210 mg Q2W improved by at least 1 anxiety category compared to 8 of 27 (30%) placebo-treated patients.²³

Over 52 weeks, HADS depression and anxiety scores continued to show a pattern of improvement among patients receiving brodalumab vs placebo.²⁵ Among patients initially receiving placebo, mean HADS depression scores were unchanged from baseline (5.3) to week 12 (5.5). After patients were switched to brodalumab 210 mg Q2W, there was a trend toward improvement between week 12 (5.4) and week 52 (3.1). Among patients initially treated with brodalumab 210 mg Q2W, mean depression scores fell from baseline (5.5) to week 12 (3.4), then rose again between weeks 12 (2.9) and 52 (3.5) in patients switched to placebo (Figure, A). The pattern of findings was similar for HADS anxiety scores (Figure, B).²⁵ Overall, brodalumab treatment appears to improve symptoms of depression and anxiety in patients being treated for psoriasis. This finding is consistent with the effects reported for other biologic therapies previously discussed.

SIB in Studies of Brodalumab
In addition to assessing the effect of brodalumab treatment on symptoms of depression and anxiety in patients with psoriasis, the brodalumab clinical trial program also tracked patterns of SIB among enrolled patients. In contrast with other clinical trials in which patients with a history of psychiatric disorders or substance abuse were excluded, clinical trials of brodalumab did not exclude patients with psychiatric disorders (eg, SIB, depression) and were therefore reflective of the real-world population of patients with moderate to severe psoriasis.²²

In a recently published, detailed analysis of psychiatric adverse events (AEs) in the brodalumab clinical trials, data related to SIB in patients with moderate to severe psoriasis were analyzed from the placebo-controlled phases and open-label, long-term extensions of a placebo-controlled phase 2 clinical trial and from the previously mentioned 3 phase 3 clinical trials.²² From the initiation of the clinical trial program, AEs were monitored during all trials. In response to completed suicides during some studies, additional SIB evaluations were later added at the request of the US Food and Drug Administration, including the Columbia Suicide Severity Rating Scale, the PHQ-8, and the Columbia Classification Algorithm for Suicide Assessment, to independently adjudicate SIB events.²²

In total, 4464 patients in the brodalumab clinical trials received at least 1 dose of brodalumab, and 4126 of these patients received at least 1 dose of brodalumab 210 mg Q2W.²² Total exposure was 9174 patient-years of brodalumab, and mean exposure was 23 months. During the 52-week controlled phases of the clinical trials, 7 patients receiving brodalumab experienced any form of SIB event, representing a time-adjusted incidence rate of 0.20 events (95% confidence interval [CI], 0.08-0.41 events) per 100 patient-years of exposure. During the same 52-week period, patients receiving the comparator drug ustekinumab had an SIB rate of 0.60 events (95% CI, 0.12-1.74 events) per 100 patient-years, which was numerically higher than the rate with brodalumab. Inferential statistical analyses were not performed, but overlapping 95% CIs around these point estimates imply a similar level of SIB risk associated with each agent in these studies. During controlled and uncontrolled treatment periods in all studies, the SIB rate among brodalumab-treated patients was 0.37 events per 100 patient-years.²²

Over all study phases, 3 completed suicides and 1 case adjudicated as indeterminate by the Columbia Classification Algorithm for Suicide Assessment review board were reported.²² All occurred in men aged 39 to 59 years. Of 6 patients with an AE of suicide attempt, all patients had at least 1 SIB risk factor and 3 had a history of SIB. The rate of SIB events was greater in patients with a history of depression (1.42) or suicidality (3.21) compared to those without any history of depression or suicidality (0.21 and 0.20, respectively).²² An examination of the regions in which the brodalumab studies were conducted showed generally consistent SIB incidence rates: 0.52, 0.29, 0.77, and 0 events per 100 patient-years in North America, Europe, Australia, and Russia, respectively.²⁴

As previously described, depression and other risk factors for SIB are prevalent among patients with psoriasis. In addition, the rate of suicide mortality has increased substantially over the last decade in the general population, particularly among middle-aged white men,²⁹ who made up much of the brodalumab clinical trial population.²² Therefore, even without treatment, it would not be surprising that SIB events occurred during the brodalumab trials. Most patients with SIB events during the trials had a history of predisposing risk factors.²² Prescribing information for brodalumab in the United States includes a boxed warning advising physicians to be aware of the risk of SIB as well as a statement that a causal relationship between SIB and brodalumab treatment has not been established.²⁷

COMMENT

This review indicates that depression is increased among patients with psoriasis regardless of treatment regimen⁷; however, the association between psoriasis and suicidality is unclear. In clinical trials of brodalumab, treatment resulted in improved symptoms of depression and anxiety among patients with psoriasis and was associated with lower rates of SIB compared to ustekinumab.^22,23

Despite the boxed warning in the brodalumab package insert concerning suicidality, a causal relationship between brodalumab treatment and increased risk of SIB has not been firmly established.²⁷ The US boxed warning is based on 3 completed suicides and 1 case adjudicated as indeterminate among more than 4000 patients who received at least 1 dose of brodalumab during global clinical trials (0.07% [3/4464]). Compliance in the Risk Evaluation and Mitigation Strategy (REMS) program is mandatory, and patient screening and counseling should not be minimized.²⁷ The 3 completed suicides occurred in patients who reported a history of financial stressors, legal difficulties, or depression and anxiety, and they occurred at least 140 days after initiation of treatment with brodalumab, a chronology that does not support a strong association between brodalumab exposure and SIB.²² Taking into consideration the increased risk for depression among individuals with psoriasis and the details surrounding the 3 completed suicides, an evidence-based causal relationship between brodalumab and increased risk for suicidality cannot be concluded. However, physicians must assess risks and benefits of any therapy in the context of the individual patient’s preferences, risk factors, and response to treatment.

Dermatologists who are aware of the comorbidity between psoriasis and mood disorders play an important role in evaluating patients with psoriasis for psychiatric risk factors.^30-32 The dermatologist should discuss with patients the relationship between psoriasis and depression, assess for any history of depression and SIB, and evaluate for signs and symptoms of depression and current SIB.³³ Screening tools, including the HADS or the short, easily administered PHQ-2³⁴ or PHQ-4,³⁵ can be used to assess whether patients have symptoms of depression.^1,36,37 Patients at risk for depression or SIB should be referred to their primary care physician or a mental health care practitioner.³⁷ Currently, there is a gap in knowledge in screening patients for psychiatric issues within the dermatology community^33,38; however, health care providers can give support to help bridge this gap.

Acknowledgments
This study was sponsored by Amgen Inc. Medical writing support was provided under the direction of the authors by Lisa Baker, PhD, and Rebecca E. Slager, PhD, of MedThink SciCom (Cary, North Carolina) and funded by Ortho Dermatologics, a division of Bausch Health US, LLC.

Psoriasis is a chronic inflammatory skin disorder that affects patients’ quality of life and social interactions.¹ Several studies have shown a strong consistent association between psoriasis and depression as well as possible suicidal ideation and behavior (SIB).^1-13 Notable findings from a 2018 review found depression prevalence ranged from 2.1% to 33.7% among patients with psoriasis vs 0% to 22.7% among unaffected patients.⁷ In a 2017 meta-analysis, Singh et al² found increased odds of SIB (odds ratio [OR], 2.05), attempted suicide (OR, 1.32), and completed suicide (OR, 1.20) in patients with psoriasis compared to those without psoriasis. In 2018, Wu and colleagues⁷ reported that odds of SIB among patients with psoriasis ranged from 1.01 to 1.94 times those of patients without psoriasis, and SIB and suicide attempts were more common than in patients with other dermatologic conditions. Koo and colleagues¹ reached similar conclusions. At the same time, the occurrence of attempted and completed suicides among patients in psoriasis clinical trials has raised concerns about whether psoriasis medications also may increase the risk for SIB.⁷

We review research on the effects of psoriasis treatment on patients’ symptoms of depression and SIB, with a focus on recent analyses of depressive symptoms and SIB among patients with psoriasis who received brodalumab in clinical trials. Finally, we suggest approaches clinicians may consider when caring for patients with psoriasis who may be at risk for depression and SIB.

MATERIALS AND METHODS

We reviewed research on the effects of biologic therapy for psoriasis on depression and SIB, with a primary focus on recent large meta-analyses. Published findings on the pattern of SIB in brodalumab clinical trials and effects of brodalumab treatment on symptoms of depression and anxiety are summarized. The most recent evidence (January 2014–December 2018) regarding the mental health comorbidities of psoriasis was assessed using published English-language research data and review articles according to a PubMed search of articles indexed for MEDLINE using the following terms: depression, anxiety, suicide, suicidal ideation and behavior, SIB, brodalumab, or psoriasis. We also reviewed citations within articles to identify relevant sources. Implications for clinical care of patients with psoriasis are discussed based on expert recommendations and the authors’ clinical experience.

RESULTS

Effects of Psoriasis Treatment on Symptoms of Depression and Suicidality

Occurrences of attempted suicide and completed suicide have been reported during treatment with several psoriasis medications,^7,9 raising concerns about whether these medications increase the risk for depression and SIB in an already vulnerable population. Wu and colleagues⁷ reviewed 11 studies published from 2006 to 2017 reporting the effects of medications for the treatment of psoriasis—adalimumab, apremilast, brodalumab, etanercept, and ustekinumab—on measures of depression and anxiety such as the Beck Depression Inventory, the Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire (PHQ) 8. In each of the 11 studies, symptoms of depression improved after treatment, over time, or compared to placebo. Notably, the magnitude of improvement in symptoms of depression was not strongly linked to the magnitude of clinical improvement.⁷ Other recent studies have reported reductions in symptoms of depression with biologic therapies, including adalimumab, etanercept, guselkumab, ixekizumab, secukinumab, and ustekinumab.^14-21

With respect to suicidality, an analysis of publicly available data found low rates of completed and attempted suicides (point estimates of 0.0–0.15 per 100 patient-years) in clinical development programs of apremilast, brodalumab, ixekizumab, and secukinumab. Patient suicidality in these trials often occurred in the context of risk factors or stressors such as work, financial difficulties, depression, and substance abuse.⁷ In a detailed 2016 analysis of suicidal behaviors during clinical trials of apremilast, brodalumab, etanercept, infliximab, ixekizumab, secukinumab, tofacitinib, ustekinumab, and other investigational agents, Gooderham and colleagues⁹ concluded that the behaviors may have resulted from the disease or patients’ psychosocial status rather than from treatment and that treatment with biologics does not increase the risk for SIB. Improvements in symptoms of depression during treatment suggest the potential to improve patients’ psychiatric outcomes with biologic treatment.⁹

Evidence From Brodalumab Studies

Intensive efforts have been made to assess the effect of brodalumab, a fully human anti–IL-17RA monoclonal antibody shown to be efficacious in the treatment of moderate to severe plaque psoriasis, on symptoms of depression and to understand the incidence of SIB among patients receiving brodalumab in clinical trials.^22-27

Depression and Anxiety in Studies of Brodalumab
To examine the effects of brodalumab on symptoms of depression, the HADS questionnaire²⁸ was administered to patients in 1 of 3 phase 3 clinical trials of brodalumab.²³ A HADS score of 0 to 7 is considered normal, 8 to 10 is mild, 11 to 14 is moderate, and 15 to 21 is severe.²³ The HADS questionnaire was administered to evaluate the presence and severity of depression and anxiety symptoms at baseline and at weeks 12, 24, 36, and 52.²⁵ This scale was not used in the other 2 phase 3 studies of brodalumab because at the time those studies were initiated, there was no indication to include mental health screenings as part of the study protocol.

Patients were initially randomized to placebo (n=220), brodalumab 140 mg every 2 weeks (Q2W; n=219), or brodalumab 210 mg Q2W (the eventual approved dose; n=222) for 12 weeks.²³ At week 12, patients initially randomized to placebo were switched to brodalumab through week 52. Patients initially randomized to brodalumab 210 mg Q2W were re-randomized to either placebo or brodalumab 210 mg Q2W.²³ Depression and anxiety were common at baseline. Based on HADS scores, depression occurred among 27% and 26% of patients randomized to brodalumab and placebo, respectively; anxiety occurred in 36% of patients in each group.²² Among patients receiving brodalumab 210 mg Q2W from baseline to week 12, HADS depression scores improved in 67% of patients and worsened in 19%. In contrast, the proportion of patients receiving placebo whose depression scores improved (45%) was similar to the proportion whose scores worsened (38%). Hospital Anxiety and Depression Scale anxiety scores also improved more often with brodalumab than with placebo.²²

Furthermore, among patients who had moderate or severe depression or anxiety at baseline, a greater percentage experienced improvement with brodalumab than placebo.²³ Among 30 patients with moderate to severe HADS depression scores at baseline who were treated with brodalumab 210 mg Q2W, 22 (73%) improved by at least 1 depression category by week 12; in the placebo group, 10 of 22 (45%) improved. Among patients with moderate or severe anxiety scores, 28 of 42 patients (67%) treated with brodalumab 210 mg Q2W improved by at least 1 anxiety category compared to 8 of 27 (30%) placebo-treated patients.²³

Over 52 weeks, HADS depression and anxiety scores continued to show a pattern of improvement among patients receiving brodalumab vs placebo.²⁵ Among patients initially receiving placebo, mean HADS depression scores were unchanged from baseline (5.3) to week 12 (5.5). After patients were switched to brodalumab 210 mg Q2W, there was a trend toward improvement between week 12 (5.4) and week 52 (3.1). Among patients initially treated with brodalumab 210 mg Q2W, mean depression scores fell from baseline (5.5) to week 12 (3.4), then rose again between weeks 12 (2.9) and 52 (3.5) in patients switched to placebo (Figure, A). The pattern of findings was similar for HADS anxiety scores (Figure, B).²⁵ Overall, brodalumab treatment appears to improve symptoms of depression and anxiety in patients being treated for psoriasis. This finding is consistent with the effects reported for other biologic therapies previously discussed.

SIB in Studies of Brodalumab
In addition to assessing the effect of brodalumab treatment on symptoms of depression and anxiety in patients with psoriasis, the brodalumab clinical trial program also tracked patterns of SIB among enrolled patients. In contrast with other clinical trials in which patients with a history of psychiatric disorders or substance abuse were excluded, clinical trials of brodalumab did not exclude patients with psychiatric disorders (eg, SIB, depression) and were therefore reflective of the real-world population of patients with moderate to severe psoriasis.²²

In a recently published, detailed analysis of psychiatric adverse events (AEs) in the brodalumab clinical trials, data related to SIB in patients with moderate to severe psoriasis were analyzed from the placebo-controlled phases and open-label, long-term extensions of a placebo-controlled phase 2 clinical trial and from the previously mentioned 3 phase 3 clinical trials.²² From the initiation of the clinical trial program, AEs were monitored during all trials. In response to completed suicides during some studies, additional SIB evaluations were later added at the request of the US Food and Drug Administration, including the Columbia Suicide Severity Rating Scale, the PHQ-8, and the Columbia Classification Algorithm for Suicide Assessment, to independently adjudicate SIB events.²²

In total, 4464 patients in the brodalumab clinical trials received at least 1 dose of brodalumab, and 4126 of these patients received at least 1 dose of brodalumab 210 mg Q2W.²² Total exposure was 9174 patient-years of brodalumab, and mean exposure was 23 months. During the 52-week controlled phases of the clinical trials, 7 patients receiving brodalumab experienced any form of SIB event, representing a time-adjusted incidence rate of 0.20 events (95% confidence interval [CI], 0.08-0.41 events) per 100 patient-years of exposure. During the same 52-week period, patients receiving the comparator drug ustekinumab had an SIB rate of 0.60 events (95% CI, 0.12-1.74 events) per 100 patient-years, which was numerically higher than the rate with brodalumab. Inferential statistical analyses were not performed, but overlapping 95% CIs around these point estimates imply a similar level of SIB risk associated with each agent in these studies. During controlled and uncontrolled treatment periods in all studies, the SIB rate among brodalumab-treated patients was 0.37 events per 100 patient-years.²²

Over all study phases, 3 completed suicides and 1 case adjudicated as indeterminate by the Columbia Classification Algorithm for Suicide Assessment review board were reported.²² All occurred in men aged 39 to 59 years. Of 6 patients with an AE of suicide attempt, all patients had at least 1 SIB risk factor and 3 had a history of SIB. The rate of SIB events was greater in patients with a history of depression (1.42) or suicidality (3.21) compared to those without any history of depression or suicidality (0.21 and 0.20, respectively).²² An examination of the regions in which the brodalumab studies were conducted showed generally consistent SIB incidence rates: 0.52, 0.29, 0.77, and 0 events per 100 patient-years in North America, Europe, Australia, and Russia, respectively.²⁴

As previously described, depression and other risk factors for SIB are prevalent among patients with psoriasis. In addition, the rate of suicide mortality has increased substantially over the last decade in the general population, particularly among middle-aged white men,²⁹ who made up much of the brodalumab clinical trial population.²² Therefore, even without treatment, it would not be surprising that SIB events occurred during the brodalumab trials. Most patients with SIB events during the trials had a history of predisposing risk factors.²² Prescribing information for brodalumab in the United States includes a boxed warning advising physicians to be aware of the risk of SIB as well as a statement that a causal relationship between SIB and brodalumab treatment has not been established.²⁷

COMMENT

This review indicates that depression is increased among patients with psoriasis regardless of treatment regimen⁷; however, the association between psoriasis and suicidality is unclear. In clinical trials of brodalumab, treatment resulted in improved symptoms of depression and anxiety among patients with psoriasis and was associated with lower rates of SIB compared to ustekinumab.^22,23

Despite the boxed warning in the brodalumab package insert concerning suicidality, a causal relationship between brodalumab treatment and increased risk of SIB has not been firmly established.²⁷ The US boxed warning is based on 3 completed suicides and 1 case adjudicated as indeterminate among more than 4000 patients who received at least 1 dose of brodalumab during global clinical trials (0.07% [3/4464]). Compliance in the Risk Evaluation and Mitigation Strategy (REMS) program is mandatory, and patient screening and counseling should not be minimized.²⁷ The 3 completed suicides occurred in patients who reported a history of financial stressors, legal difficulties, or depression and anxiety, and they occurred at least 140 days after initiation of treatment with brodalumab, a chronology that does not support a strong association between brodalumab exposure and SIB.²² Taking into consideration the increased risk for depression among individuals with psoriasis and the details surrounding the 3 completed suicides, an evidence-based causal relationship between brodalumab and increased risk for suicidality cannot be concluded. However, physicians must assess risks and benefits of any therapy in the context of the individual patient’s preferences, risk factors, and response to treatment.

Dermatologists who are aware of the comorbidity between psoriasis and mood disorders play an important role in evaluating patients with psoriasis for psychiatric risk factors.^30-32 The dermatologist should discuss with patients the relationship between psoriasis and depression, assess for any history of depression and SIB, and evaluate for signs and symptoms of depression and current SIB.³³ Screening tools, including the HADS or the short, easily administered PHQ-2³⁴ or PHQ-4,³⁵ can be used to assess whether patients have symptoms of depression.^1,36,37 Patients at risk for depression or SIB should be referred to their primary care physician or a mental health care practitioner.³⁷ Currently, there is a gap in knowledge in screening patients for psychiatric issues within the dermatology community^33,38; however, health care providers can give support to help bridge this gap.

Acknowledgments
This study was sponsored by Amgen Inc. Medical writing support was provided under the direction of the authors by Lisa Baker, PhD, and Rebecca E. Slager, PhD, of MedThink SciCom (Cary, North Carolina) and funded by Ortho Dermatologics, a division of Bausch Health US, LLC.

Psoriasis is a chronic inflammatory skin disorder that affects patients’ quality of life and social interactions.¹ Several studies have shown a strong consistent association between psoriasis and depression as well as possible suicidal ideation and behavior (SIB).^1-13 Notable findings from a 2018 review found depression prevalence ranged from 2.1% to 33.7% among patients with psoriasis vs 0% to 22.7% among unaffected patients.⁷ In a 2017 meta-analysis, Singh et al² found increased odds of SIB (odds ratio [OR], 2.05), attempted suicide (OR, 1.32), and completed suicide (OR, 1.20) in patients with psoriasis compared to those without psoriasis. In 2018, Wu and colleagues⁷ reported that odds of SIB among patients with psoriasis ranged from 1.01 to 1.94 times those of patients without psoriasis, and SIB and suicide attempts were more common than in patients with other dermatologic conditions. Koo and colleagues¹ reached similar conclusions. At the same time, the occurrence of attempted and completed suicides among patients in psoriasis clinical trials has raised concerns about whether psoriasis medications also may increase the risk for SIB.⁷

We review research on the effects of psoriasis treatment on patients’ symptoms of depression and SIB, with a focus on recent analyses of depressive symptoms and SIB among patients with psoriasis who received brodalumab in clinical trials. Finally, we suggest approaches clinicians may consider when caring for patients with psoriasis who may be at risk for depression and SIB.

MATERIALS AND METHODS

We reviewed research on the effects of biologic therapy for psoriasis on depression and SIB, with a primary focus on recent large meta-analyses. Published findings on the pattern of SIB in brodalumab clinical trials and effects of brodalumab treatment on symptoms of depression and anxiety are summarized. The most recent evidence (January 2014–December 2018) regarding the mental health comorbidities of psoriasis was assessed using published English-language research data and review articles according to a PubMed search of articles indexed for MEDLINE using the following terms: depression, anxiety, suicide, suicidal ideation and behavior, SIB, brodalumab, or psoriasis. We also reviewed citations within articles to identify relevant sources. Implications for clinical care of patients with psoriasis are discussed based on expert recommendations and the authors’ clinical experience.

RESULTS

Effects of Psoriasis Treatment on Symptoms of Depression and Suicidality

Occurrences of attempted suicide and completed suicide have been reported during treatment with several psoriasis medications,^7,9 raising concerns about whether these medications increase the risk for depression and SIB in an already vulnerable population. Wu and colleagues⁷ reviewed 11 studies published from 2006 to 2017 reporting the effects of medications for the treatment of psoriasis—adalimumab, apremilast, brodalumab, etanercept, and ustekinumab—on measures of depression and anxiety such as the Beck Depression Inventory, the Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire (PHQ) 8. In each of the 11 studies, symptoms of depression improved after treatment, over time, or compared to placebo. Notably, the magnitude of improvement in symptoms of depression was not strongly linked to the magnitude of clinical improvement.⁷ Other recent studies have reported reductions in symptoms of depression with biologic therapies, including adalimumab, etanercept, guselkumab, ixekizumab, secukinumab, and ustekinumab.^14-21

With respect to suicidality, an analysis of publicly available data found low rates of completed and attempted suicides (point estimates of 0.0–0.15 per 100 patient-years) in clinical development programs of apremilast, brodalumab, ixekizumab, and secukinumab. Patient suicidality in these trials often occurred in the context of risk factors or stressors such as work, financial difficulties, depression, and substance abuse.⁷ In a detailed 2016 analysis of suicidal behaviors during clinical trials of apremilast, brodalumab, etanercept, infliximab, ixekizumab, secukinumab, tofacitinib, ustekinumab, and other investigational agents, Gooderham and colleagues⁹ concluded that the behaviors may have resulted from the disease or patients’ psychosocial status rather than from treatment and that treatment with biologics does not increase the risk for SIB. Improvements in symptoms of depression during treatment suggest the potential to improve patients’ psychiatric outcomes with biologic treatment.⁹

Evidence From Brodalumab Studies

Intensive efforts have been made to assess the effect of brodalumab, a fully human anti–IL-17RA monoclonal antibody shown to be efficacious in the treatment of moderate to severe plaque psoriasis, on symptoms of depression and to understand the incidence of SIB among patients receiving brodalumab in clinical trials.^22-27

Depression and Anxiety in Studies of Brodalumab
To examine the effects of brodalumab on symptoms of depression, the HADS questionnaire²⁸ was administered to patients in 1 of 3 phase 3 clinical trials of brodalumab.²³ A HADS score of 0 to 7 is considered normal, 8 to 10 is mild, 11 to 14 is moderate, and 15 to 21 is severe.²³ The HADS questionnaire was administered to evaluate the presence and severity of depression and anxiety symptoms at baseline and at weeks 12, 24, 36, and 52.²⁵ This scale was not used in the other 2 phase 3 studies of brodalumab because at the time those studies were initiated, there was no indication to include mental health screenings as part of the study protocol.

Patients were initially randomized to placebo (n=220), brodalumab 140 mg every 2 weeks (Q2W; n=219), or brodalumab 210 mg Q2W (the eventual approved dose; n=222) for 12 weeks.²³ At week 12, patients initially randomized to placebo were switched to brodalumab through week 52. Patients initially randomized to brodalumab 210 mg Q2W were re-randomized to either placebo or brodalumab 210 mg Q2W.²³ Depression and anxiety were common at baseline. Based on HADS scores, depression occurred among 27% and 26% of patients randomized to brodalumab and placebo, respectively; anxiety occurred in 36% of patients in each group.²² Among patients receiving brodalumab 210 mg Q2W from baseline to week 12, HADS depression scores improved in 67% of patients and worsened in 19%. In contrast, the proportion of patients receiving placebo whose depression scores improved (45%) was similar to the proportion whose scores worsened (38%). Hospital Anxiety and Depression Scale anxiety scores also improved more often with brodalumab than with placebo.²²

Furthermore, among patients who had moderate or severe depression or anxiety at baseline, a greater percentage experienced improvement with brodalumab than placebo.²³ Among 30 patients with moderate to severe HADS depression scores at baseline who were treated with brodalumab 210 mg Q2W, 22 (73%) improved by at least 1 depression category by week 12; in the placebo group, 10 of 22 (45%) improved. Among patients with moderate or severe anxiety scores, 28 of 42 patients (67%) treated with brodalumab 210 mg Q2W improved by at least 1 anxiety category compared to 8 of 27 (30%) placebo-treated patients.²³

Over 52 weeks, HADS depression and anxiety scores continued to show a pattern of improvement among patients receiving brodalumab vs placebo.²⁵ Among patients initially receiving placebo, mean HADS depression scores were unchanged from baseline (5.3) to week 12 (5.5). After patients were switched to brodalumab 210 mg Q2W, there was a trend toward improvement between week 12 (5.4) and week 52 (3.1). Among patients initially treated with brodalumab 210 mg Q2W, mean depression scores fell from baseline (5.5) to week 12 (3.4), then rose again between weeks 12 (2.9) and 52 (3.5) in patients switched to placebo (Figure, A). The pattern of findings was similar for HADS anxiety scores (Figure, B).²⁵ Overall, brodalumab treatment appears to improve symptoms of depression and anxiety in patients being treated for psoriasis. This finding is consistent with the effects reported for other biologic therapies previously discussed.

SIB in Studies of Brodalumab
In addition to assessing the effect of brodalumab treatment on symptoms of depression and anxiety in patients with psoriasis, the brodalumab clinical trial program also tracked patterns of SIB among enrolled patients. In contrast with other clinical trials in which patients with a history of psychiatric disorders or substance abuse were excluded, clinical trials of brodalumab did not exclude patients with psychiatric disorders (eg, SIB, depression) and were therefore reflective of the real-world population of patients with moderate to severe psoriasis.²²

In a recently published, detailed analysis of psychiatric adverse events (AEs) in the brodalumab clinical trials, data related to SIB in patients with moderate to severe psoriasis were analyzed from the placebo-controlled phases and open-label, long-term extensions of a placebo-controlled phase 2 clinical trial and from the previously mentioned 3 phase 3 clinical trials.²² From the initiation of the clinical trial program, AEs were monitored during all trials. In response to completed suicides during some studies, additional SIB evaluations were later added at the request of the US Food and Drug Administration, including the Columbia Suicide Severity Rating Scale, the PHQ-8, and the Columbia Classification Algorithm for Suicide Assessment, to independently adjudicate SIB events.²²

In total, 4464 patients in the brodalumab clinical trials received at least 1 dose of brodalumab, and 4126 of these patients received at least 1 dose of brodalumab 210 mg Q2W.²² Total exposure was 9174 patient-years of brodalumab, and mean exposure was 23 months. During the 52-week controlled phases of the clinical trials, 7 patients receiving brodalumab experienced any form of SIB event, representing a time-adjusted incidence rate of 0.20 events (95% confidence interval [CI], 0.08-0.41 events) per 100 patient-years of exposure. During the same 52-week period, patients receiving the comparator drug ustekinumab had an SIB rate of 0.60 events (95% CI, 0.12-1.74 events) per 100 patient-years, which was numerically higher than the rate with brodalumab. Inferential statistical analyses were not performed, but overlapping 95% CIs around these point estimates imply a similar level of SIB risk associated with each agent in these studies. During controlled and uncontrolled treatment periods in all studies, the SIB rate among brodalumab-treated patients was 0.37 events per 100 patient-years.²²

Over all study phases, 3 completed suicides and 1 case adjudicated as indeterminate by the Columbia Classification Algorithm for Suicide Assessment review board were reported.²² All occurred in men aged 39 to 59 years. Of 6 patients with an AE of suicide attempt, all patients had at least 1 SIB risk factor and 3 had a history of SIB. The rate of SIB events was greater in patients with a history of depression (1.42) or suicidality (3.21) compared to those without any history of depression or suicidality (0.21 and 0.20, respectively).²² An examination of the regions in which the brodalumab studies were conducted showed generally consistent SIB incidence rates: 0.52, 0.29, 0.77, and 0 events per 100 patient-years in North America, Europe, Australia, and Russia, respectively.²⁴

As previously described, depression and other risk factors for SIB are prevalent among patients with psoriasis. In addition, the rate of suicide mortality has increased substantially over the last decade in the general population, particularly among middle-aged white men,²⁹ who made up much of the brodalumab clinical trial population.²² Therefore, even without treatment, it would not be surprising that SIB events occurred during the brodalumab trials. Most patients with SIB events during the trials had a history of predisposing risk factors.²² Prescribing information for brodalumab in the United States includes a boxed warning advising physicians to be aware of the risk of SIB as well as a statement that a causal relationship between SIB and brodalumab treatment has not been established.²⁷

COMMENT

This review indicates that depression is increased among patients with psoriasis regardless of treatment regimen⁷; however, the association between psoriasis and suicidality is unclear. In clinical trials of brodalumab, treatment resulted in improved symptoms of depression and anxiety among patients with psoriasis and was associated with lower rates of SIB compared to ustekinumab.^22,23

Despite the boxed warning in the brodalumab package insert concerning suicidality, a causal relationship between brodalumab treatment and increased risk of SIB has not been firmly established.²⁷ The US boxed warning is based on 3 completed suicides and 1 case adjudicated as indeterminate among more than 4000 patients who received at least 1 dose of brodalumab during global clinical trials (0.07% [3/4464]). Compliance in the Risk Evaluation and Mitigation Strategy (REMS) program is mandatory, and patient screening and counseling should not be minimized.²⁷ The 3 completed suicides occurred in patients who reported a history of financial stressors, legal difficulties, or depression and anxiety, and they occurred at least 140 days after initiation of treatment with brodalumab, a chronology that does not support a strong association between brodalumab exposure and SIB.²² Taking into consideration the increased risk for depression among individuals with psoriasis and the details surrounding the 3 completed suicides, an evidence-based causal relationship between brodalumab and increased risk for suicidality cannot be concluded. However, physicians must assess risks and benefits of any therapy in the context of the individual patient’s preferences, risk factors, and response to treatment.

Dermatologists who are aware of the comorbidity between psoriasis and mood disorders play an important role in evaluating patients with psoriasis for psychiatric risk factors.^30-32 The dermatologist should discuss with patients the relationship between psoriasis and depression, assess for any history of depression and SIB, and evaluate for signs and symptoms of depression and current SIB.³³ Screening tools, including the HADS or the short, easily administered PHQ-2³⁴ or PHQ-4,³⁵ can be used to assess whether patients have symptoms of depression.^1,36,37 Patients at risk for depression or SIB should be referred to their primary care physician or a mental health care practitioner.³⁷ Currently, there is a gap in knowledge in screening patients for psychiatric issues within the dermatology community^33,38; however, health care providers can give support to help bridge this gap.

Acknowledgments
This study was sponsored by Amgen Inc. Medical writing support was provided under the direction of the authors by Lisa Baker, PhD, and Rebecca E. Slager, PhD, of MedThink SciCom (Cary, North Carolina) and funded by Ortho Dermatologics, a division of Bausch Health US, LLC.

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

LAS VEGAS – Recent research is offering new insights into psoriasis and alopecia in the pediatric population, a dermatologist told colleagues, and it’s time to be on the lookout for psoriasis linked to treatment with tumor necrosis factor (TNF) inhibitors.

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics, at the University of California, San Diego, offered these tips and comments in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

Psoriasis

It’s a brand new day for adult psoriasis sufferers, but it seems to be only a brand new morning for their pediatric counterparts. “Kids and teenagers were left behind in the biologic revolution,” Dr. Eichenfield said. “Only two systemic biologics have been approved for psoriasis in children.” They are ustekinumab (Stelara), approved by the Food and Drug Administration for treating psoriasis in children aged 12 years and older, and etanercept, approved for aged 4 years and older.

The good news, he said, is that “our new biologic agents are now being studied in children.”

Research is also providing new insight into pediatric psoriasis, said Dr. Eichenfield, who is also chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. It’s now clear that “there’s a lot more facial involvement, and a high involvement of scalp and nail,” he noted.

It’s also clear, he said, that inflammation begins early in pediatric psoriasis. That raises the question of whether it’s a good idea to launch aggressive treatment to stop the “psoriatic march” toward cardiovascular and other medical problems down the line, he commented.

“Keep an open mind to getting aggressive in therapy,” he advised, although he acknowledged that “it’s hard to get beyond the two biologics, and only one is approved for children under 12.”

Dr. Eichenfield advised colleagues to keep an eye out for TNF inhibitor–induced psoriasis. “We’re seeing it pretty regularly,” he said, commonly in children who are treated with TNF inhibitors for rheumatoid arthritis or Crohn’s disease.

The lesions “look like dermatitis but are very psoriasiform,” he said, and research suggests this can appear after a single dose or after as many as 63 months of treatment. Topical and light therapy can be helpful. But if those treatments do not help, he said, it’s time to consider changing the biologic that the patient is taking. “Is the biologic adequately controlling their underlying disease? If not, you can help find one that would be great for their underlying disease and clear up their psoriasis.”

Alopecia

Pediatric alopecia “is a problem I see pretty regularly in practice,” Dr. Eichenfield said. When he sees patients with alopecia, he says that, “‘if your child doesn’t have 50% hair loss, you’re in the good group. It will generally heal up and never come back again.’ ”

He referred to a recent study, where investigators at the Children’s Hospital of Philadelphia retrospectively studied 125 children under age 4 years who were diagnosed with alopecia areata and followed for 2 years. Over time, those children with over 50% of hair loss initially were more likely to have worsening Severity of Alopecia Tool (SALT) scores over the follow-up period. But a high proportion of those with mild alopecia initially continued to have mild alopecia at follow-up (Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990).

Dr. Eichenfield noted that the study found that 41% of the patients also had atopic dermatitis.

He also highlighted two other recent studies on pediatric alopecia: One found that while vitamin D levels were low in a majority of children with alopecia in the study, the proportion who had a deficiency was similar to the proportion in a larger pediatric population, at about 22% in both groups (J Am Acad Dermatol. 2018 Sep;79(3):e43-e44). Supplementation doesn’t seem to help. “It’s not important to test levels,” he said.

Another study examined whether it’s a good idea to test patients for celiac disease in children with alopecia (Pediatr Dermatol. 2018 Jul;35[4]:535-8). Some parents may ask this question, but the answer, he said, is generally no.

What’s next? “We were hoping oral and topical JAK inhibitors would work well” in this population, Dr. Eichenfield said, but study findings haven’t been promising.

Still, oral tofacitinib (Xeljanz) showed some “pretty impressive” success in a recent study in four children, he noted. Based on the results, the authors wrote that “we suggest that, after proper counseling regarding the risks, including severe infection and malignancy, the use of tofacitinib may be considered for preadolescent children with AA [alopecia areata] who are experiencing psychosocial impairment” (J Am Acad Dermatol. 2019 Feb;80[2]:568-70).

In general, Dr. Eichenfield said, research on pediatric alopecia “will be secondary, especially with JAK inhibitors because of the risk of side effects. But [children will] probably tolerate them better than adults do because they have fewer medical problems.”

Meanwhile, he added, controversy continues to swirl around how to treat children over age 10 years who have lost 50% or more of their hair. “I’ve seen hundreds of kids with alopecia areata,” he said, “and I can’t predict what the course may be.”

Dr. Eichenfield reports multiple relationships (consultant or investigator) with various pharmaceutical companies, including Abbvie, Allergan, Lilly, Novartis, and others. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Recent research is offering new insights into psoriasis and alopecia in the pediatric population, a dermatologist told colleagues, and it’s time to be on the lookout for psoriasis linked to treatment with tumor necrosis factor (TNF) inhibitors.

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics, at the University of California, San Diego, offered these tips and comments in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

Psoriasis

It’s a brand new day for adult psoriasis sufferers, but it seems to be only a brand new morning for their pediatric counterparts. “Kids and teenagers were left behind in the biologic revolution,” Dr. Eichenfield said. “Only two systemic biologics have been approved for psoriasis in children.” They are ustekinumab (Stelara), approved by the Food and Drug Administration for treating psoriasis in children aged 12 years and older, and etanercept, approved for aged 4 years and older.

The good news, he said, is that “our new biologic agents are now being studied in children.”

Research is also providing new insight into pediatric psoriasis, said Dr. Eichenfield, who is also chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. It’s now clear that “there’s a lot more facial involvement, and a high involvement of scalp and nail,” he noted.

It’s also clear, he said, that inflammation begins early in pediatric psoriasis. That raises the question of whether it’s a good idea to launch aggressive treatment to stop the “psoriatic march” toward cardiovascular and other medical problems down the line, he commented.

“Keep an open mind to getting aggressive in therapy,” he advised, although he acknowledged that “it’s hard to get beyond the two biologics, and only one is approved for children under 12.”

Dr. Eichenfield advised colleagues to keep an eye out for TNF inhibitor–induced psoriasis. “We’re seeing it pretty regularly,” he said, commonly in children who are treated with TNF inhibitors for rheumatoid arthritis or Crohn’s disease.

The lesions “look like dermatitis but are very psoriasiform,” he said, and research suggests this can appear after a single dose or after as many as 63 months of treatment. Topical and light therapy can be helpful. But if those treatments do not help, he said, it’s time to consider changing the biologic that the patient is taking. “Is the biologic adequately controlling their underlying disease? If not, you can help find one that would be great for their underlying disease and clear up their psoriasis.”

Alopecia

Pediatric alopecia “is a problem I see pretty regularly in practice,” Dr. Eichenfield said. When he sees patients with alopecia, he says that, “‘if your child doesn’t have 50% hair loss, you’re in the good group. It will generally heal up and never come back again.’ ”

He referred to a recent study, where investigators at the Children’s Hospital of Philadelphia retrospectively studied 125 children under age 4 years who were diagnosed with alopecia areata and followed for 2 years. Over time, those children with over 50% of hair loss initially were more likely to have worsening Severity of Alopecia Tool (SALT) scores over the follow-up period. But a high proportion of those with mild alopecia initially continued to have mild alopecia at follow-up (Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990).

Dr. Eichenfield noted that the study found that 41% of the patients also had atopic dermatitis.

He also highlighted two other recent studies on pediatric alopecia: One found that while vitamin D levels were low in a majority of children with alopecia in the study, the proportion who had a deficiency was similar to the proportion in a larger pediatric population, at about 22% in both groups (J Am Acad Dermatol. 2018 Sep;79(3):e43-e44). Supplementation doesn’t seem to help. “It’s not important to test levels,” he said.

Another study examined whether it’s a good idea to test patients for celiac disease in children with alopecia (Pediatr Dermatol. 2018 Jul;35[4]:535-8). Some parents may ask this question, but the answer, he said, is generally no.

What’s next? “We were hoping oral and topical JAK inhibitors would work well” in this population, Dr. Eichenfield said, but study findings haven’t been promising.

Still, oral tofacitinib (Xeljanz) showed some “pretty impressive” success in a recent study in four children, he noted. Based on the results, the authors wrote that “we suggest that, after proper counseling regarding the risks, including severe infection and malignancy, the use of tofacitinib may be considered for preadolescent children with AA [alopecia areata] who are experiencing psychosocial impairment” (J Am Acad Dermatol. 2019 Feb;80[2]:568-70).

In general, Dr. Eichenfield said, research on pediatric alopecia “will be secondary, especially with JAK inhibitors because of the risk of side effects. But [children will] probably tolerate them better than adults do because they have fewer medical problems.”

Meanwhile, he added, controversy continues to swirl around how to treat children over age 10 years who have lost 50% or more of their hair. “I’ve seen hundreds of kids with alopecia areata,” he said, “and I can’t predict what the course may be.”

Dr. Eichenfield reports multiple relationships (consultant or investigator) with various pharmaceutical companies, including Abbvie, Allergan, Lilly, Novartis, and others. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Recent research is offering new insights into psoriasis and alopecia in the pediatric population, a dermatologist told colleagues, and it’s time to be on the lookout for psoriasis linked to treatment with tumor necrosis factor (TNF) inhibitors.

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics, at the University of California, San Diego, offered these tips and comments in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

Psoriasis

It’s a brand new day for adult psoriasis sufferers, but it seems to be only a brand new morning for their pediatric counterparts. “Kids and teenagers were left behind in the biologic revolution,” Dr. Eichenfield said. “Only two systemic biologics have been approved for psoriasis in children.” They are ustekinumab (Stelara), approved by the Food and Drug Administration for treating psoriasis in children aged 12 years and older, and etanercept, approved for aged 4 years and older.

The good news, he said, is that “our new biologic agents are now being studied in children.”

Research is also providing new insight into pediatric psoriasis, said Dr. Eichenfield, who is also chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego. It’s now clear that “there’s a lot more facial involvement, and a high involvement of scalp and nail,” he noted.

It’s also clear, he said, that inflammation begins early in pediatric psoriasis. That raises the question of whether it’s a good idea to launch aggressive treatment to stop the “psoriatic march” toward cardiovascular and other medical problems down the line, he commented.

“Keep an open mind to getting aggressive in therapy,” he advised, although he acknowledged that “it’s hard to get beyond the two biologics, and only one is approved for children under 12.”

Dr. Eichenfield advised colleagues to keep an eye out for TNF inhibitor–induced psoriasis. “We’re seeing it pretty regularly,” he said, commonly in children who are treated with TNF inhibitors for rheumatoid arthritis or Crohn’s disease.

The lesions “look like dermatitis but are very psoriasiform,” he said, and research suggests this can appear after a single dose or after as many as 63 months of treatment. Topical and light therapy can be helpful. But if those treatments do not help, he said, it’s time to consider changing the biologic that the patient is taking. “Is the biologic adequately controlling their underlying disease? If not, you can help find one that would be great for their underlying disease and clear up their psoriasis.”

Alopecia

Pediatric alopecia “is a problem I see pretty regularly in practice,” Dr. Eichenfield said. When he sees patients with alopecia, he says that, “‘if your child doesn’t have 50% hair loss, you’re in the good group. It will generally heal up and never come back again.’ ”

He referred to a recent study, where investigators at the Children’s Hospital of Philadelphia retrospectively studied 125 children under age 4 years who were diagnosed with alopecia areata and followed for 2 years. Over time, those children with over 50% of hair loss initially were more likely to have worsening Severity of Alopecia Tool (SALT) scores over the follow-up period. But a high proportion of those with mild alopecia initially continued to have mild alopecia at follow-up (Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990).

Dr. Eichenfield noted that the study found that 41% of the patients also had atopic dermatitis.

He also highlighted two other recent studies on pediatric alopecia: One found that while vitamin D levels were low in a majority of children with alopecia in the study, the proportion who had a deficiency was similar to the proportion in a larger pediatric population, at about 22% in both groups (J Am Acad Dermatol. 2018 Sep;79(3):e43-e44). Supplementation doesn’t seem to help. “It’s not important to test levels,” he said.

Another study examined whether it’s a good idea to test patients for celiac disease in children with alopecia (Pediatr Dermatol. 2018 Jul;35[4]:535-8). Some parents may ask this question, but the answer, he said, is generally no.

What’s next? “We were hoping oral and topical JAK inhibitors would work well” in this population, Dr. Eichenfield said, but study findings haven’t been promising.

Still, oral tofacitinib (Xeljanz) showed some “pretty impressive” success in a recent study in four children, he noted. Based on the results, the authors wrote that “we suggest that, after proper counseling regarding the risks, including severe infection and malignancy, the use of tofacitinib may be considered for preadolescent children with AA [alopecia areata] who are experiencing psychosocial impairment” (J Am Acad Dermatol. 2019 Feb;80[2]:568-70).

In general, Dr. Eichenfield said, research on pediatric alopecia “will be secondary, especially with JAK inhibitors because of the risk of side effects. But [children will] probably tolerate them better than adults do because they have fewer medical problems.”

Meanwhile, he added, controversy continues to swirl around how to treat children over age 10 years who have lost 50% or more of their hair. “I’ve seen hundreds of kids with alopecia areata,” he said, “and I can’t predict what the course may be.”

Dr. Eichenfield reports multiple relationships (consultant or investigator) with various pharmaceutical companies, including Abbvie, Allergan, Lilly, Novartis, and others. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – While biologics have dramatically changed the picture, drugs like methotrexate, acitretin, cyclosporine, and apremilast still have roles to play in the treatment of psoriasis, a dermatologist told colleagues.

However, caution is necessary, especially when the drugs are used in combination with biologics, Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn., said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Dr. Strober offered these tips about the proper use of these four drugs in psoriasis patients:

Acitretin (Soriatane). “This was used as monotherapy initially, but at this point in history, fewer and fewer patients are getting it as monotherapy,” he said. A dose of 25 mg/day appears to provide the best mix of efficacy and side-effect control, “although it’s not a high-efficacy drug, especially at 25 mg a day. It’s a slow-acting drug, and you may need 4 if not 6 months to see the maximum effect before you give up on it.”

What about using acitretin in combination with other therapies? Studies examining its use with phototherapy haven’t been promising, Dr. Strober said. The drug can be used with methotrexate, he said, even though the combination will worry pharmacists. “Follow the liver, and you’ll be fine” he noted. “That combination can be successful. Laboratory monitoring is not onerous: Discontinue after a few months if you’ve not seen any movement.” The drug can also be used with biologics, he said.

Apremilast (Otezla). This drug will bring about a third of patients to a Psoriasis Area and Severity Index (PASI) 75. “That’s not the most impressive efficacy. Rarely do we clear patients with this drug, and it has tolerability issues in some patients,” Dr. Strober said. Side effects can include diarrhea, nausea, headache, and depression. “Warn patients of these possibilities,” he added.

Methotrexate. “It’s very helpful and not a drug to be feared if it’s monitored correctly,” Dr. Strober said. “It’s certainly not a biologic, but it’s not a bad drug from an efficacy standpoint, and it does have efficacy in psoriatic arthritis.”

The drug’s low cost can make it a good alternative to biologics in patients with limited insurance options – such as those on Medicare – or those who don’t have insurance, he said.

“Psoriasis is often controlled at a mean dose of 15 mg/week [orally], with no test dose; start at 15-mg weekly,” he said. “It’s an interesting drug that allows you to dose weekly and still get efficacy,” especially when dosed subcutaneously.

Beware the many contraindications such as pregnancy, possible pregnancy, and high alcohol intake, he added. Dr. Strober doesn’t recommend liver biopsies to monitor hepatic effects. “It’s a poor test with risk and sampling error,” he said.

Cyclosporine. This drug is best “in severe patients in need of a quick response,” said Dr. Strober, who added that biologics are often a better option even in patients who are sensitive to price since samples and free-drug programs are available. “It’s in and out of the body quickly, and most people skip doses and get recurrence of their disease quickly,” he said.

Blood tests are a hassle for patients, he said, and “people often don’t feel great on the drug,” said Dr. Strober, who added, however, that he still does occasionally use it.

Dr. Strober reported multiple disclosures including consultant/advisory board (AbbVie, Amgen, Lilly, Pfizer, among others) and investigator relationships. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – While biologics have dramatically changed the picture, drugs like methotrexate, acitretin, cyclosporine, and apremilast still have roles to play in the treatment of psoriasis, a dermatologist told colleagues.

However, caution is necessary, especially when the drugs are used in combination with biologics, Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn., said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Dr. Strober offered these tips about the proper use of these four drugs in psoriasis patients:

Acitretin (Soriatane). “This was used as monotherapy initially, but at this point in history, fewer and fewer patients are getting it as monotherapy,” he said. A dose of 25 mg/day appears to provide the best mix of efficacy and side-effect control, “although it’s not a high-efficacy drug, especially at 25 mg a day. It’s a slow-acting drug, and you may need 4 if not 6 months to see the maximum effect before you give up on it.”

What about using acitretin in combination with other therapies? Studies examining its use with phototherapy haven’t been promising, Dr. Strober said. The drug can be used with methotrexate, he said, even though the combination will worry pharmacists. “Follow the liver, and you’ll be fine” he noted. “That combination can be successful. Laboratory monitoring is not onerous: Discontinue after a few months if you’ve not seen any movement.” The drug can also be used with biologics, he said.

Apremilast (Otezla). This drug will bring about a third of patients to a Psoriasis Area and Severity Index (PASI) 75. “That’s not the most impressive efficacy. Rarely do we clear patients with this drug, and it has tolerability issues in some patients,” Dr. Strober said. Side effects can include diarrhea, nausea, headache, and depression. “Warn patients of these possibilities,” he added.

Methotrexate. “It’s very helpful and not a drug to be feared if it’s monitored correctly,” Dr. Strober said. “It’s certainly not a biologic, but it’s not a bad drug from an efficacy standpoint, and it does have efficacy in psoriatic arthritis.”

The drug’s low cost can make it a good alternative to biologics in patients with limited insurance options – such as those on Medicare – or those who don’t have insurance, he said.

“Psoriasis is often controlled at a mean dose of 15 mg/week [orally], with no test dose; start at 15-mg weekly,” he said. “It’s an interesting drug that allows you to dose weekly and still get efficacy,” especially when dosed subcutaneously.

Beware the many contraindications such as pregnancy, possible pregnancy, and high alcohol intake, he added. Dr. Strober doesn’t recommend liver biopsies to monitor hepatic effects. “It’s a poor test with risk and sampling error,” he said.

Cyclosporine. This drug is best “in severe patients in need of a quick response,” said Dr. Strober, who added that biologics are often a better option even in patients who are sensitive to price since samples and free-drug programs are available. “It’s in and out of the body quickly, and most people skip doses and get recurrence of their disease quickly,” he said.

Blood tests are a hassle for patients, he said, and “people often don’t feel great on the drug,” said Dr. Strober, who added, however, that he still does occasionally use it.

Dr. Strober reported multiple disclosures including consultant/advisory board (AbbVie, Amgen, Lilly, Pfizer, among others) and investigator relationships. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – While biologics have dramatically changed the picture, drugs like methotrexate, acitretin, cyclosporine, and apremilast still have roles to play in the treatment of psoriasis, a dermatologist told colleagues.

However, caution is necessary, especially when the drugs are used in combination with biologics, Bruce E. Strober, MD, PhD, of Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn., said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Dr. Strober offered these tips about the proper use of these four drugs in psoriasis patients:

Acitretin (Soriatane). “This was used as monotherapy initially, but at this point in history, fewer and fewer patients are getting it as monotherapy,” he said. A dose of 25 mg/day appears to provide the best mix of efficacy and side-effect control, “although it’s not a high-efficacy drug, especially at 25 mg a day. It’s a slow-acting drug, and you may need 4 if not 6 months to see the maximum effect before you give up on it.”

What about using acitretin in combination with other therapies? Studies examining its use with phototherapy haven’t been promising, Dr. Strober said. The drug can be used with methotrexate, he said, even though the combination will worry pharmacists. “Follow the liver, and you’ll be fine” he noted. “That combination can be successful. Laboratory monitoring is not onerous: Discontinue after a few months if you’ve not seen any movement.” The drug can also be used with biologics, he said.

Apremilast (Otezla). This drug will bring about a third of patients to a Psoriasis Area and Severity Index (PASI) 75. “That’s not the most impressive efficacy. Rarely do we clear patients with this drug, and it has tolerability issues in some patients,” Dr. Strober said. Side effects can include diarrhea, nausea, headache, and depression. “Warn patients of these possibilities,” he added.

Methotrexate. “It’s very helpful and not a drug to be feared if it’s monitored correctly,” Dr. Strober said. “It’s certainly not a biologic, but it’s not a bad drug from an efficacy standpoint, and it does have efficacy in psoriatic arthritis.”

The drug’s low cost can make it a good alternative to biologics in patients with limited insurance options – such as those on Medicare – or those who don’t have insurance, he said.

“Psoriasis is often controlled at a mean dose of 15 mg/week [orally], with no test dose; start at 15-mg weekly,” he said. “It’s an interesting drug that allows you to dose weekly and still get efficacy,” especially when dosed subcutaneously.

Beware the many contraindications such as pregnancy, possible pregnancy, and high alcohol intake, he added. Dr. Strober doesn’t recommend liver biopsies to monitor hepatic effects. “It’s a poor test with risk and sampling error,” he said.

Cyclosporine. This drug is best “in severe patients in need of a quick response,” said Dr. Strober, who added that biologics are often a better option even in patients who are sensitive to price since samples and free-drug programs are available. “It’s in and out of the body quickly, and most people skip doses and get recurrence of their disease quickly,” he said.

Blood tests are a hassle for patients, he said, and “people often don’t feel great on the drug,” said Dr. Strober, who added, however, that he still does occasionally use it.

Dr. Strober reported multiple disclosures including consultant/advisory board (AbbVie, Amgen, Lilly, Pfizer, among others) and investigator relationships. SDEF and this news organization are owned by the same parent company.

ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

[email protected]

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

[email protected]

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

[email protected]

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

MADRID – Psoriasis patients with a new prescription for oral apremilast were significantly less likely to switch to a different therapy within the next 12 months than were patients on their first tumor necrosis factor (TNF) inhibitor, in a large retrospective national propensity score-matched study.

Bruce Jancin/MDedge News

“This was surprising to us,” David L. Kaplan, MD, admitted in presenting the study findings at the annual congress of the European Academy of Dermatology and Venereology.

The surprise came because apremilast, a phosphodiesterase 4 (PDE4)-inhibitor, is less potent than the injectable biologics at driving down Psoriasis Area and Severity Index (PASI) scores.

“This is real-world data. And this is what patients are saying at 1 year: that they’re actually happier [with apremilast] and they’re not interested in changing,” said Dr. Kaplan, a dermatologist at the University of Kansas and in private practice in Overland Park, Kan.

He and his coinvestigators tapped the IBM Watson MarketScan health insurance claims database for 2015-2016 and identified 1,645 biologic-naive adults with psoriasis who started on apremilast therapy and an equal number of biologic-naive psoriasis patients who initiated treatment with a biologic, of whom 1,207 started on an TNF inhibitor and 438 began on an interleukin inhibitor, which was ustekinumab in 81% of cases. The TNF inhibitor cohort was split 80/20 between adalimumab and etanercept. The three groups – new users of apremilast, a TNF inhibitor, or an interleukin inhibitor – were propensity-matched based upon age, prior usage of systemic psoriasis therapies, Charlson Comorbidity Index scores, and other potential confounders.

The primary endpoint was the switch rate to a different psoriasis treatment within 12 months. The switch rate was significantly lower in patients who had started on apremilast than in those on a TNF inhibitor by a margin of 14% to 25%, while the 11% switch rate among patients on an interleukin inhibitor was not significantly different from the rate in the apremilast group.

“I think this data kind of gives us pause,” the dermatologist said. “As a clinician myself, when patients come back in the first question I always ask is, ‘How’re you doing? Are you happy?’ And at the end of the day, the data in terms of switch rates shows where patients are at. And that doesn’t really follow what we see with PASI scores.”

A secondary endpoint was the switch rate through 24 months. The same pattern held true: 24.9% in the apremilast starters, which was similar to the 22.9% in patients initiated on an interleukin inhibitor, and significantly less than the 39.1% rate in the TNF inhibitor group.

Among patients who switched medications within the first 12 months, the mean number of days to the switch was similar across all three groups.

The study had several limitations. Propensity score–matching is not a cure-all that can eradicate all potential biases. And the claims database didn’t include information on why patients switched, nor what their PASI scores were. “This is real-world data, and clinicians don’t do PASI scores in the real world,” he noted.

Audience member Andrew Blauvelt, MD, a dermatologist and president of the Oregon Medical Research Center, Portland, rose to challenge Dr. Kaplan’s conclusion that patients on apremilast were happier with their care.

“How can you rule out that it’s just practices that don’t use biologics, and they’re keeping patients on apremilast regardless of whether they’re better or happy because they’re not using biologics?” inquired Dr. Blauvelt.

Dr. Kaplan conceded that might well be a partial explanation for the results.

“Reluctance to use biologics is out there,” he agreed.

Dr. Kaplan reported serving as a consultant and paid speaker for Celgene, the study sponsor, as well as several other pharmaceutical companies.

[email protected]

SOURCE: Kaplan DL. EADV Abstract FC04.04.

MADRID – Psoriasis patients with a new prescription for oral apremilast were significantly less likely to switch to a different therapy within the next 12 months than were patients on their first tumor necrosis factor (TNF) inhibitor, in a large retrospective national propensity score-matched study.

Bruce Jancin/MDedge News

“This was surprising to us,” David L. Kaplan, MD, admitted in presenting the study findings at the annual congress of the European Academy of Dermatology and Venereology.

The surprise came because apremilast, a phosphodiesterase 4 (PDE4)-inhibitor, is less potent than the injectable biologics at driving down Psoriasis Area and Severity Index (PASI) scores.

“This is real-world data. And this is what patients are saying at 1 year: that they’re actually happier [with apremilast] and they’re not interested in changing,” said Dr. Kaplan, a dermatologist at the University of Kansas and in private practice in Overland Park, Kan.

He and his coinvestigators tapped the IBM Watson MarketScan health insurance claims database for 2015-2016 and identified 1,645 biologic-naive adults with psoriasis who started on apremilast therapy and an equal number of biologic-naive psoriasis patients who initiated treatment with a biologic, of whom 1,207 started on an TNF inhibitor and 438 began on an interleukin inhibitor, which was ustekinumab in 81% of cases. The TNF inhibitor cohort was split 80/20 between adalimumab and etanercept. The three groups – new users of apremilast, a TNF inhibitor, or an interleukin inhibitor – were propensity-matched based upon age, prior usage of systemic psoriasis therapies, Charlson Comorbidity Index scores, and other potential confounders.

The primary endpoint was the switch rate to a different psoriasis treatment within 12 months. The switch rate was significantly lower in patients who had started on apremilast than in those on a TNF inhibitor by a margin of 14% to 25%, while the 11% switch rate among patients on an interleukin inhibitor was not significantly different from the rate in the apremilast group.

“I think this data kind of gives us pause,” the dermatologist said. “As a clinician myself, when patients come back in the first question I always ask is, ‘How’re you doing? Are you happy?’ And at the end of the day, the data in terms of switch rates shows where patients are at. And that doesn’t really follow what we see with PASI scores.”

A secondary endpoint was the switch rate through 24 months. The same pattern held true: 24.9% in the apremilast starters, which was similar to the 22.9% in patients initiated on an interleukin inhibitor, and significantly less than the 39.1% rate in the TNF inhibitor group.

Among patients who switched medications within the first 12 months, the mean number of days to the switch was similar across all three groups.

The study had several limitations. Propensity score–matching is not a cure-all that can eradicate all potential biases. And the claims database didn’t include information on why patients switched, nor what their PASI scores were. “This is real-world data, and clinicians don’t do PASI scores in the real world,” he noted.

Audience member Andrew Blauvelt, MD, a dermatologist and president of the Oregon Medical Research Center, Portland, rose to challenge Dr. Kaplan’s conclusion that patients on apremilast were happier with their care.

“How can you rule out that it’s just practices that don’t use biologics, and they’re keeping patients on apremilast regardless of whether they’re better or happy because they’re not using biologics?” inquired Dr. Blauvelt.

Dr. Kaplan conceded that might well be a partial explanation for the results.

“Reluctance to use biologics is out there,” he agreed.

Dr. Kaplan reported serving as a consultant and paid speaker for Celgene, the study sponsor, as well as several other pharmaceutical companies.

[email protected]

SOURCE: Kaplan DL. EADV Abstract FC04.04.

MADRID – Psoriasis patients with a new prescription for oral apremilast were significantly less likely to switch to a different therapy within the next 12 months than were patients on their first tumor necrosis factor (TNF) inhibitor, in a large retrospective national propensity score-matched study.

Bruce Jancin/MDedge News

“This was surprising to us,” David L. Kaplan, MD, admitted in presenting the study findings at the annual congress of the European Academy of Dermatology and Venereology.

The surprise came because apremilast, a phosphodiesterase 4 (PDE4)-inhibitor, is less potent than the injectable biologics at driving down Psoriasis Area and Severity Index (PASI) scores.

“This is real-world data. And this is what patients are saying at 1 year: that they’re actually happier [with apremilast] and they’re not interested in changing,” said Dr. Kaplan, a dermatologist at the University of Kansas and in private practice in Overland Park, Kan.

He and his coinvestigators tapped the IBM Watson MarketScan health insurance claims database for 2015-2016 and identified 1,645 biologic-naive adults with psoriasis who started on apremilast therapy and an equal number of biologic-naive psoriasis patients who initiated treatment with a biologic, of whom 1,207 started on an TNF inhibitor and 438 began on an interleukin inhibitor, which was ustekinumab in 81% of cases. The TNF inhibitor cohort was split 80/20 between adalimumab and etanercept. The three groups – new users of apremilast, a TNF inhibitor, or an interleukin inhibitor – were propensity-matched based upon age, prior usage of systemic psoriasis therapies, Charlson Comorbidity Index scores, and other potential confounders.

The primary endpoint was the switch rate to a different psoriasis treatment within 12 months. The switch rate was significantly lower in patients who had started on apremilast than in those on a TNF inhibitor by a margin of 14% to 25%, while the 11% switch rate among patients on an interleukin inhibitor was not significantly different from the rate in the apremilast group.

“I think this data kind of gives us pause,” the dermatologist said. “As a clinician myself, when patients come back in the first question I always ask is, ‘How’re you doing? Are you happy?’ And at the end of the day, the data in terms of switch rates shows where patients are at. And that doesn’t really follow what we see with PASI scores.”

A secondary endpoint was the switch rate through 24 months. The same pattern held true: 24.9% in the apremilast starters, which was similar to the 22.9% in patients initiated on an interleukin inhibitor, and significantly less than the 39.1% rate in the TNF inhibitor group.

Among patients who switched medications within the first 12 months, the mean number of days to the switch was similar across all three groups.

The study had several limitations. Propensity score–matching is not a cure-all that can eradicate all potential biases. And the claims database didn’t include information on why patients switched, nor what their PASI scores were. “This is real-world data, and clinicians don’t do PASI scores in the real world,” he noted.

Audience member Andrew Blauvelt, MD, a dermatologist and president of the Oregon Medical Research Center, Portland, rose to challenge Dr. Kaplan’s conclusion that patients on apremilast were happier with their care.

“How can you rule out that it’s just practices that don’t use biologics, and they’re keeping patients on apremilast regardless of whether they’re better or happy because they’re not using biologics?” inquired Dr. Blauvelt.

Dr. Kaplan conceded that might well be a partial explanation for the results.

“Reluctance to use biologics is out there,” he agreed.

Dr. Kaplan reported serving as a consultant and paid speaker for Celgene, the study sponsor, as well as several other pharmaceutical companies.

[email protected]

SOURCE: Kaplan DL. EADV Abstract FC04.04.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]