Distribution of Depression and Suicidality in a Psoriasis Clinical Trial Population Steven R. Feldman,1 Susan Harris,2 Shipra Rastogi,3 Robert J. Israel2 1Wake Forest University School of Medicine, Winston-Salem, NC; 2Valeant Pharmaceuticals North America LLC, Bridgewater, NJ; 3Ortho Dermatologics, Bridgewater, NJ Winter Clinical Dermatology Conference - Hawaii® • January 12-17, 2018 • Lahaina, HI SYNOPSIS • Patients with psoriasis have an increased risk of depression and suicidal ideation and behavior (SIB)1,2 • Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody that antagonizes the action of specific inflammatory cytokines involved in psoriasis3 • One multicenter, randomized, placebo-controlled phase 3 trial (AMAGINE-1), 2 multicenter, randomized, placebo- and active comparator–controlled phase 3 trials (AMAGINE-2/-3), and one phase 2 trial demonstrated the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis3-5 • All regions involved in the trials reported baseline rates of depression and SIB • Rates of SIB events were low throughout all trials (range, 0 to 0.77 per 100 patient-years [PY]) OBJECTIVE • This analysis evaluated rates of depression adverse events (AEs) and SIB in patients participating in one phase 2 and three phase 3 clinical trials of brodalumab METHODS Study design • Pooled data for all trials in patients who received any dose of brodalumab are included • Of note, the brodalumab trials had no exclusions based on the presence or history of psychiatric disorders or substance abuse Endpoints/Assessments • Rates of depression AEs and SIB (intentional self-injury, suicidal behavior, suicide attempt, and completed suicide) in the United States, Canada, Europe, Australia, and Russia were assessed at baseline and throughout the trials RESULTS Patient demographics and baseline disease characteristics • A total of 4464 patients received brodalumab, with cumulative exposure times of 3672.6 PY in the US (n=1937), 1473.4 PY in Canada (n=631), 3492.7 PY in Europe (n=1651), 388.8 PY in Australia (n=180), and 134.4 PY in Russia (n=65) Safety • At baseline, depression was observed across most study regions, which is representative of the psoriasis population (Figure 1) • Depression AE rate in PY from the first dose of brodalumab through end of study was also consistent across regions (Figure 2) • SIB was observed at baseline across all countries involved in the 4 trials (Figure 3) • Follow-up observation time-adjusted incidence rates of SIB events from the first dose of brodalumab through end of study were consistent across regions (Figure 4) Acknowledgments: Medical writing support was provided by MedThink SciCom and was funded by Ortho Dermatologics. This study was sponsored by Amgen Inc. Author disclosures: The authors disclose past or current financial relationships with the following companies: Feldman – AbbVie, Advance Medical, Almirall, Anacor, Astellas, Baxter, Boehringer Ingelheim, Caremark, Celgene, Cosmederm Bioscience, Galderma, GlaxoSmithKline/Stiefel, Informa, Janssen, LEO Pharma, Eli Lilly & Co, Merck, Merz, Mylan, National Biological Corporation, National Psoriasis Foundation, Novan, Novartis, Parion, Pfizer, Qurient, Regeneron, Suncare Research, Taro, UpToDate, Valeant Pharmaceuticals North America LLC, Gerson Lehrman, Guidepoint Global, www.DrScore.com, and Causa Research; Harris – Valeant Pharmaceuticals North America LLC; Israel – Valeant Pharmaceuticals North America LLC; and Rastogi – Ortho Dermatologics and Valeant Pharmaceuticals North America LLC. References: 1. Kurd SKK et al. Arch Dermatol. 2010;146:891-895. 2. Koo J et al. J Eur Acad Dermatol Venereol. 2017 [Epub ahead of print]. 3. Lebwohl M et al. N Engl J Med. 2015;373:1318-1328. 4. Papp KA et al. Br J Dermatol. 2016;175:273-286. 5. Papp KA et al. N Engl J Med. 2012;366:1181-1189. CONCLUSIONS • Clinical trials of brodalumab reflected real-world populations of patients with moderate-to-severe psoriasis • The patients in these 4 trials had baseline rates of depression and SIB that were consistent with those in other studies2 • The follow-up observation time-adjusted incidence rates (per 100 PY) of SIB events from the first dose of brodalumab through end of study were consistent across regions © 2017. All Rights Reserved. 5.7% 0% 22.7% 20% 18.6% Figure 1. Incidence of depression at baseline across geographic regions in patients who received any dose of brodalumab in any of the 4 trials. Number of patients who had valid measurements at baseline: United States, 1937; Canada, 631; Europe, 1651; Australia, 180; and Russia, 65. In ci de nc e ra te o f S IB pe r 10 0 pa ti en t- ye ar s 3 0 2 1 5 4 0.52 United States 0.14 Canada 0.29 Europe 0.77 Australia 0 Russia Figure 4. Follow-up observation time-adjusted incidence rates (per 100 patient-years) of SIB events from the first dose of brodalumab through end of study in patients from the long-term extension of any of the 4 trials. SIB, suicidal ideation and behavior. Total patient-year exposure for each region: United States, 3672.6; Canada, 1473.4; Europe, 3492.7; Australia, 388.8; and Russia, 134.4. T im e- ad ju st ed d ep re ss io n ad ve rs e ev en t ra te pe r 10 0 pa ti en t- ye ar s 3 0 2 1 5 4 2.8 United States 2.9 Canada 1.6 Europe 4.6 Australia 1.5 Russia Figure 2. Depression adverse event rate in patient-years from the first dose of brodalumab through end of study. Total patient-year exposure for each region: United States, 3680.9; Canada, 1473.5; Europe, 3496.3; Australia, 388.9; and Russia, 134.4. 1.8% 3.1% 6.7% 2.8% 3.8% Figure 3. Incidence of baseline SIB across geographic regions in patients who received any dose of brodalumab in any of the 4 trials. SIB, suicidal ideation and behavior. Number of patients who had valid measurements at baseline: United States, 1937; Canada, 631; Europe, 1651; Australia, 180; and Russia, 65.