Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials - 13/12/17
, Kim A. Papp, MD, PhD, FRCPC b, Lauren B. Marangell, MD c, d, John Koo, MD e, Andrew Blauvelt, MD, MBA f, Melinda Gooderham, MD g, Jashin J. Wu, MD h, Shipra Rastogi, PhD i, Susan Harris, MS i, Radhakrishnan Pillai, PhD j, Robert J. Israel, MD iAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : adverse events, depression, mental health, psoriasis, psychiatric, psychiatry, suicidal ideation and behavior
Abbreviations used : AE, C-SSRS, eC-SSRS, HADS, IL, SIB, PY
Plan
| Funding sources: None. |
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| Disclosure: Dr Mark Lebwohl is an employee of Mount Sinai, which receives research funds from Amgen, Anacor Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen Biotech, Kadmon Corporation, LEO Pharma, MedImmune, Novartis, Pfizer, Sun Pharmaceutical Industries, and Valeant Pharmaceuticals North America LLC. Dr Papp has served as a consultant, scientific officer, or member of a speaker's bureau, advisory board, or steering committee or received research grants or honoraria from AbbVie, Akesis Pharmaceuticals, Akros, Allergan, Alza Corporation; Amgen, Anacor Pharmaceuticals, Artax Biopharma; Pharma, AstraZeneca, Baxter, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite BioPharma, Celgene Corporation, Celtic Pharma, Cipher Pharmaceuticals, Dermira, Dow Pharma, Eli Lilly, Ferring Pharmaceuticals, Formycon AG, Forward Pharma A/S; Fujisawa Pharmaceuticals, Funxional Therapeutics, Galderma SA, Genentech, Genexion SA, Genzyme Corporation, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck (Merck Sharp and Dohme), Merck Serono, Mitsubishi Tanabe Pharma, Mylan, Novartis, NovImmune SA, Pan-Genetics Pharmaceutical Corporation, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi-Aventis US, Stiefel Laboratories, Takeda Pharmaceuticals, UCB, Valeant Pharmaceuticals North America, and Vertex Pharmaceuticals. Dr Marangell is a former employee and stockholder of Eli Lilly and a paid consultant for Valeant Pharmaceuticals North America. Dr Koo is a speaker, advisor, and consultant for Pfizer, Anacor, Novartis, Celgene, Janssen, Eli Lilly, Photomedex, Regeneron, Amgen, Sun, Valeant Pharmaceuticals North America LLC, LEO, AbbVie, and Galderma. Dr Blauvelt has served as a scientific adviser and clinical study investigator for AbbVie, Aclaris Therapeutics, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene Corporation, Dermavant, Dermira, Eli Lilly, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, LEO Pharma, Merck, Novartis, Pfizer, Purdue Pharma, Regeneron Pharmaceuticals, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharmaceutical Industries, UCB, Valeant Pharmaceuticals North America, and Vidac, and he has served as a paid speaker for Eli Lilly, Janssen, Regeneron Pharmaceuticals, and Sanofi Genzyme. Dr. Gooderham has been an advisory board member, clinical investigator, and/or speaker for AbbVie, Akros, Amgen, Boehringer Ingelheim, Celgene Corporation, Dermira, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Kyowa Hakko Kirin, LEO Pharma, Eli Lilly, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Sun Pharmaceuticals Industries, Takeda Pharmaceuticals, UCB, and Valeant Pharmaceuticals North America LLC. Dr. Wu is an investigator for AbbVie, Amgen, Eli Lilly, Janssen Pharmaceuticals, Novartis, and Regeneron Pharmaceuticals. Dr Rastogi, Ms Harris, and Dr Israel are employees of Valeant Pharmaceuticals North America LLC and may hold stock and/or stock options in the company. Dr Pillai is an employee of Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals North America LLC) and may hold stock and/or stock options in the company. |
Vol 78 - N° 1
P. 81 - janvier 2018 Retour au numéro
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