Mark G Lebwohl1, Kim A Papp2, Lauren B Marangell3, John Koo4, Andrew Blauvelt5, Melinda Gooderham6, Jashin J Wu7, Shipra Rastogi8, Susan Harris8, Radhakrishnan Pillai9, Robert J Israel8. 1. Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: lebwohl@aol.com. 2. K. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada. 3. The McGovern School of Medicine of the University of Texas, Houston, Texas; Brain Health Consultants, Houston, Texas. 4. University of California San Francisco Psoriasis and Skin Treatment Center, San Francisco, California. 5. Oregon Medical Research Center, Portland, Oregon. 6. Skin Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada. 7. Kaiser Permanente Los Angeles Medical Center, Los Angeles, California. 8. Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey. 9. Dow Pharmaceutical (a division of Valeant Pharmaceuticals North America LLC), Petaluma, California.
Abstract
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.
RCT Entities:
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.
Authors: Ryan Rivera-Oyola; Roselyn Stanger; Graham H Litchman; Quinn Thibodeaux; John Koo; Richard Fried; Gary Goldenberg; George Han; Sylvia Hsu; Leon Kircik; Melissa Knuckles; Andrea Murina; Jeffrey Weinberg; Jashin J Wu; Mark Lebwohl Journal: J Clin Aesthet Dermatol Date: 2020-12-01
Authors: John W Frew; Kristina Navrazhina; David Grand; Mary Sullivan-Whalen; Patricia Gilleaudeau; Sandra Garcet; Jonathan Ungar; James G Krueger Journal: J Am Acad Dermatol Date: 2020-05-13 Impact factor: 11.527