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Mark Lebwohl - One of the best experts on this subject based on the ideXlab platform.
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Two-Year US Pharmacovigilance Report on Brodalumab
Dermatology and Therapy, 2020Co-Authors: Mark Lebwohl, Craig Leonardi, April Armstrong, Nicole Rawnsley, Mohammed Merchant, Binu Alexander, Abby JacobsonAbstract:Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, Brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between Brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took Brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. Methods This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the Brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. Results Data were collected from 2677 patients in the United States who took Brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn’s disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to Brodalumab. Conclusions This pharmacovigilance report supports the safety profile of Brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.
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recapture rate of Brodalumab in patients with a lapse in treatment
Journal of Drugs in Dermatology, 2020Co-Authors: Mark Lebwohl, April W. Armstrong, Abby S. Van Voorhees, Jennifer Clay Cather, Abby JacobsonAbstract:The National Psoriasis Foundation has emphasized the importance of achieving skin clearance targets throughout the course of treatment. However, patients with psoriasis often stop and restart treatment for reasons such as psychological distress, dissatisfaction with treatment, inconvenience, cost, or comorbidities. Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of moderate-to-severe plaque psoriasis. This review discusses the efficacy and safety of Brodalumab and other biologic therapies in patients with psoriasis who stop and restart treatment. These clinically relevant and important findings can help inform real-world treatment decisions. J Drugs Dermatol. 2020;19(4):384-387. doi:10.36849/JDD.2020.5026.
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Malignancy Rates in Brodalumab Clinical Studies for Psoriasis
American Journal of Clinical Dermatology, 2020Co-Authors: Alice Gottlieb, Mark Lebwohl, Robert J. Israel, Abby JacobsonAbstract:Background Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis. Objective This study summarizes malignancy rates in psoriasis clinical studies of Brodalumab. Methods Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of Brodalumab for the treatment of psoriasis, including two studies with randomization to Brodalumab, ustekinumab, or placebo. Data from the 52-week (Brodalumab and ustekinumab) and long-term (Brodalumab) pools were summarized as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY). Results Exposure-adjusted event rates per 100 PY at 52 weeks were lower with Brodalumab ( n = 4019; 3446 total PY of exposure) than with ustekinumab ( n = 613; 495 total PY of exposure), including adjudicated malignancies (0.9 vs 2.6) and Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies (0.3 vs 0.4). The exposure-adjusted event rate of adjudicated malignancies in the Brodalumab group remained stable in the long-term analysis (0.9 [82 events]). Conclusions Rates of malignancy among Brodalumab-treated patients with psoriasis were generally low. Trial registry ClinicalTrials.gov identifier NCT00975637; NCT01101100; NCT01708590 (AMAGINE-1); NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).
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Expert Panel Discussion among Psoriasis and Psychodermatology Specialists: How Best to Manage Depressed Psoriasis Patients with Brodalumab
SKIN The Journal of Cutaneous Medicine, 2019Co-Authors: Quinn Thibodeaux, Mark Lebwohl, Sylvia Hsu, Graham H Litchman, Gary Goldenberg, George Han, Rick Fried, Melissa Knuckles, Leon Kircik, Andrea MurinaAbstract:Psoriasis patients with comorbid depression represent a common therapeutic challenge for dermatologists. Depressed patients often require the practicing dermatologist to go outside of their comfort zone, and the FDA’s labeling of medications such as Brodalumab have further complicated an already difficult-to-treat patient population. A multi-disciplinary work-group consisting of a board-certified psychiatrist, a licensed clinical psychologist, and multiple dermatologists was convened to formulate practical recommendations for the evaluation and treatment of this at-risk population. How to broach the subject of depression and when to refer patients for formal evaluation were discussed. The expert panel also produced a consensus statement regarding the use of Brodalumab in patients with both psoriasis and depression.
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Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study.
American journal of clinical dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to
Abby Jacobson - One of the best experts on this subject based on the ideXlab platform.
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Two-Year US Pharmacovigilance Report on Brodalumab
Dermatology and Therapy, 2020Co-Authors: Mark Lebwohl, Craig Leonardi, April Armstrong, Nicole Rawnsley, Mohammed Merchant, Binu Alexander, Abby JacobsonAbstract:Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, Brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between Brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took Brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. Methods This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the Brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. Results Data were collected from 2677 patients in the United States who took Brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn’s disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to Brodalumab. Conclusions This pharmacovigilance report supports the safety profile of Brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.
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Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics.
Dermatology and therapy, 2020Co-Authors: Alan Menter, April W. Armstrong, Abby S. Van Voorhees, Clive Liu, Abby JacobsonAbstract:While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of Brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with Brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with Brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that Brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.
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recapture rate of Brodalumab in patients with a lapse in treatment
Journal of Drugs in Dermatology, 2020Co-Authors: Mark Lebwohl, April W. Armstrong, Abby S. Van Voorhees, Jennifer Clay Cather, Abby JacobsonAbstract:The National Psoriasis Foundation has emphasized the importance of achieving skin clearance targets throughout the course of treatment. However, patients with psoriasis often stop and restart treatment for reasons such as psychological distress, dissatisfaction with treatment, inconvenience, cost, or comorbidities. Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of moderate-to-severe plaque psoriasis. This review discusses the efficacy and safety of Brodalumab and other biologic therapies in patients with psoriasis who stop and restart treatment. These clinically relevant and important findings can help inform real-world treatment decisions. J Drugs Dermatol. 2020;19(4):384-387. doi:10.36849/JDD.2020.5026.
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Malignancy Rates in Brodalumab Clinical Studies for Psoriasis
American Journal of Clinical Dermatology, 2020Co-Authors: Alice Gottlieb, Mark Lebwohl, Robert J. Israel, Abby JacobsonAbstract:Background Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis. Objective This study summarizes malignancy rates in psoriasis clinical studies of Brodalumab. Methods Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of Brodalumab for the treatment of psoriasis, including two studies with randomization to Brodalumab, ustekinumab, or placebo. Data from the 52-week (Brodalumab and ustekinumab) and long-term (Brodalumab) pools were summarized as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY). Results Exposure-adjusted event rates per 100 PY at 52 weeks were lower with Brodalumab ( n = 4019; 3446 total PY of exposure) than with ustekinumab ( n = 613; 495 total PY of exposure), including adjudicated malignancies (0.9 vs 2.6) and Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies (0.3 vs 0.4). The exposure-adjusted event rate of adjudicated malignancies in the Brodalumab group remained stable in the long-term analysis (0.9 [82 events]). Conclusions Rates of malignancy among Brodalumab-treated patients with psoriasis were generally low. Trial registry ClinicalTrials.gov identifier NCT00975637; NCT01101100; NCT01708590 (AMAGINE-1); NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).
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Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study.
American journal of clinical dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to
Alan Menter - One of the best experts on this subject based on the ideXlab platform.
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Long-term efficacy and safety of Brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1).
The British journal of dermatology, 2020Co-Authors: Kim A Papp, Alan Menter, C. Leonardi, J. Soung, S. Weiss, Radhakrishnan Pillai, A. JacobsonAbstract:BACKGROUND Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVES To evaluate the efficacy and safety of Brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS At baseline, patients were randomized to Brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with Brodalumab were rerandomized to Brodalumab (n = 83) or placebo (n = 84; later re-treated with Brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to Brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events. RESULTS Among those who achieved sPGA 0/1 at week 12 and were rerandomized to Brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from Brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from Brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving Brodalumab after placebo. No new safety signals were observed. CONCLUSIONS These findings indicate that Brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.
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Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics.
Dermatology and therapy, 2020Co-Authors: Alan Menter, April W. Armstrong, Abby S. Van Voorhees, Clive Liu, Abby JacobsonAbstract:While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of Brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with Brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with Brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that Brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.
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Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study.
American journal of clinical dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to
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efficacy safety and patient reported outcomes in patients with moderate to severe plaque psoriasis treated with Brodalumab for 5 years in a long term open label phase ii study
American Journal of Clinical Dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged. Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. NCT01101100.
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No Elevated Risk for Depression, Anxiety, or Suicidality with Secukinumab in a Pooled Analysis of Data from 10 Clinical Studies in Moderate-to-Severe Plaque Psoriasis
The British journal of dermatology, 2017Co-Authors: Bruce E. Strober, Alan Menter, Richard G Langley, Michelle Magid, Brian Porter, Todd Fox, J. Safi, Charis PapavassilisAbstract:Concerns have emerged over the potential for Brodalumab, a monoclonal antibody that binds to the human interleukin (IL)-17 receptor A and blocks the activity of multiple IL-17 isoforms, to increase risk of suicidal ideation and behaviour. Although the validity of this association has been questioned,1,2 Brodalumab has a boxed warning regarding suicidality in its US label and is only available through a Risk Evaluation and Mitigation Strategy. Regardless of the true association between suicidality and Brodalumab, the demonstrated adverse impact of psoriasis on mental health necessitates careful assessment for possible psychiatric adverse effects of psoriasis therapies, including those that inhibit the IL-17 pathway. This article is protected by copyright. All rights reserved.
Kim Papp - One of the best experts on this subject based on the ideXlab platform.
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Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study.
American journal of clinical dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to
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efficacy safety and patient reported outcomes in patients with moderate to severe plaque psoriasis treated with Brodalumab for 5 years in a long term open label phase ii study
American Journal of Clinical Dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged. Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. NCT01101100.
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impact of previous biologic use on the efficacy and safety of Brodalumab and ustekinumab in patients with moderate to severe plaque psoriasis integrated analysis of the randomized controlled trials amagine 2 and amagine 3
British Journal of Dermatology, 2018Co-Authors: Kim Papp, Radhakrishnan Pillai, Mark Lebwohl, Kenneth B. Gordon, Richard G Langley, Alice B Gottlieb, Shipra Rastogi, Robert J. IsraelAbstract:BACKGROUND Biologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics. OBJECTIVES To investigate the impact of previous biologic exposure on the efficacy and safety of Brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS Two placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with Brodalumab [210 mg or 140 mg every 2 weeks (Q2W)], ustekinumab or placebo. Efficacy end points included ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout. RESULTS In total, 493 patients [334 (27%) Brodalumab 210 mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40·9% and 39·5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21·1% and 17·0% with ustekinumab (both P < 0·001). In patients where prior biologics had been successful or failed, 41·7% and 32·0% achieved PASI 100, compared with 21·1% and 11·3% with ustekinumab. Tolerability was similar, and did not appear to be influenced by previous treatment with biologics. CONCLUSIONS The efficacy of Brodalumab 210 mg Q2W was similar regardless of prior biological therapy (P = 0·31, 0·32 and 0·64 for PASI 75, 90 and 100, respectively). Almost twice as many patients achieved PASI 100 or complete clearance with Brodalumab at week 12 compared with ustekinumab; the differences were most noticeable where previous biologics had failed. Both treatments were well tolerated.
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Impact of previous biologic use on the efficacy and safety of Brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE-2 and AMAGINE-3.
The British journal of dermatology, 2018Co-Authors: Kim Papp, Radhakrishnan Pillai, Mark Lebwohl, Kenneth B. Gordon, Richard G Langley, Alice B Gottlieb, Shipra Rastogi, Robert J. IsraelAbstract:BACKGROUND Biologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics. OBJECTIVES To investigate the impact of previous biologic exposure on the efficacy and safety of Brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS Two placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with Brodalumab [210 mg or 140 mg every 2 weeks (Q2W)], ustekinumab or placebo. Efficacy end points included ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout. RESULTS In total, 493 patients [334 (27%) Brodalumab 210 mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40·9% and 39·5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21·1% and 17·0% with ustekinumab (both P
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Psychiatric adverse events during treatment with Brodalumab: Analysis of psoriasis clinical trials
Journal of the American Academy of Dermatology, 2017Co-Authors: Mark Lebwohl, John Koo, Kim Papp, Andrew Blauvelt, Shipra Rastogi, Lauren B. Marangell, Melinda Gooderham, Susan Harris, Radhakrishnan PillaiAbstract:Background Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). Objective To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with Brodalumab, a fully human anti–interleukin 17 receptor A monoclonal antibody. Methods Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. Results The analysis included 4464 patients with 9161.8 patient-years of Brodalumab exposure. The follow-up time–adjusted incidence rates of SIB events were comparable between the Brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the Brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. Limitations There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Conclusions Comparison with controls and the timing of events do not indicate a causal relationship between SIB and Brodalumab treatment.
Radhakrishnan Pillai - One of the best experts on this subject based on the ideXlab platform.
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Long-term efficacy and safety of Brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1).
The British journal of dermatology, 2020Co-Authors: Kim A Papp, Alan Menter, C. Leonardi, J. Soung, S. Weiss, Radhakrishnan Pillai, A. JacobsonAbstract:BACKGROUND Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVES To evaluate the efficacy and safety of Brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS At baseline, patients were randomized to Brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with Brodalumab were rerandomized to Brodalumab (n = 83) or placebo (n = 84; later re-treated with Brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to Brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events. RESULTS Among those who achieved sPGA 0/1 at week 12 and were rerandomized to Brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from Brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from Brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving Brodalumab after placebo. No new safety signals were observed. CONCLUSIONS These findings indicate that Brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.
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Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study.
American journal of clinical dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to
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efficacy safety and patient reported outcomes in patients with moderate to severe plaque psoriasis treated with Brodalumab for 5 years in a long term open label phase ii study
American Journal of Clinical Dermatology, 2019Co-Authors: Mark Lebwohl, Alan Menter, Radhakrishnan Pillai, Kim Papp, Andrew Blauvelt, Scott Guenthner, Robert Israel, Abby JacobsonAbstract:Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. The aim of the study was to assess the long-term efficacy and safety of Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Patients who completed a 12-week, phase II, dose-ranging clinical trial received Brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Overall, 181 patients received Brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged. Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. NCT01101100.
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Efficacy and safety of Brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials.
The British journal of dermatology, 2018Co-Authors: Richard G Langley, Radhakrishnan Pillai, Mark Lebwohl, Andrew Blauvelt, Sylvia Hsu, Shipra Rastogi, April W. Armstrong, S. K. Tyring, Robert J. IsraelAbstract:Background Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has demonstrated superior efficacy and safety over ustekinumab as induction therapy for moderate-to-severe psoriasis. Objectives To evaluate the efficacy and safety of Brodalumab through week 52 in patients who had inadequate responses to ustekinumab. Methods A subgroup analysis of the phase III AMAGINE-2/-3 double-blind randomized controlled trials was performed. Participants were aged 18-75 years and had a Psoriasis Area and Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and involvement of ≥ 10% body surface area. The studies were registered at ClinicalTrials.gov: AMAGINE-2, NCT01708603; AMAGINE-3, NCT01708629. Results At baseline, patients with or without prior biologic experience who had an adequate response at week 16 on ustekinumab or Brodalumab had lower rates of involved body surface area, PASI, prior biologic use, psoriatic arthritis and body mass index than patients who experienced inadequate response at or after week 16. Among patients who experienced inadequate response to ustekinumab, those rescued with Brodalumab had PASI ≥ 75%, ≥ 90% and 100% improvement response rates of 72·6%, 58·1% and 36·3%, respectively, at week 52 compared with 61·7%, 25·5% and 5·4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with Brodalumab (377·3 adverse events per 100 patient-years) and those who remained on ustekinumab (389·9 adverse events per 100 patient-years). Conclusions Among patients who experienced inadequate responses to ustekinumab, rescue with Brodalumab improved skin clearance outcomes compared with continuing ustekinumab.
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improvement in itch and other psoriasis symptoms with Brodalumab in phase 3 randomized controlled trials
Journal of The European Academy of Dermatology and Venereology, 2018Co-Authors: Alice B Gottlieb, Radhakrishnan Pillai, Kenneth B. Gordon, Sylvia Hsu, Shipra Rastogi, Leon H Kircik, Boni E Elewski, Lawrence F Eichenfield, Robert J. IsraelAbstract:BACKGROUND Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of Brodalumab, an interleukin-17 receptor A antagonist, in treating moderate-to-severe psoriasis have been reported in three randomized, controlled, phase 3 trials (AMAGINE-1/-2/-3). OBJECTIVE The effect of Brodalumab on lesional symptoms was assessed using the psoriasis symptom inventory (PSI), a validated patient-reported instrument. METHODS Patients were randomized to receive Brodalumab (140 or 210 mg every 2 weeks [Q2W]), placebo (AMAGINE-1/-2/-3), or ustekinumab (AMAGINE-2/-3) during a 12-week induction phase, followed by a maintenance phase through week 52. Patients electronically rated the severity of PSI items (itch, burning, stinging, pain, redness, scaling, cracking and flaking) during the previous 24 h on a scale of 0 (not at all severe) to 4 (very severe). At each visit, the PSI total score responder status was assessed, with responders defined as having an average weekly total inventory score ≤8 with no item score >1 at week 12. RESULTS Across AMAGINE-1/-2/-3, Brodalumab was associated with improvements in PSI total scores and itch scores vs. placebo from week 2 through week 12 (P < 0.001 in both domains). In AMAGINE-2/-3, Brodalumab 210 mg Q2W demonstrated faster onset of PSI total score and itch responses (week 2, 22.1% and 36.4%, respectively) vs. ustekinumab (week 2, 6.9% and 17.1%, respectively) and was associated with improved itch responses vs. ustekinumab after 52 weeks of constant treatment. CONCLUSION Brodalumab demonstrated rapid, robust improvements in symptoms assessed by the PSI, including itch, vs. placebo and ustekinumab.