Efficacy and Safety of Brodalumab in Obese Patients With Moderate-to-Severe Plaque Psoriasis Abby S. Van Voorhees,1 Sylvia Hsu,2 Boni Elewski,3 Shipra Rastogi,4 Robert J. Israel5 1Eastern Virginia Medical School, Norfolk, VA; 2Temple University School of Medicine, Philadelphia, PA; 3University of Alabama at Birmingham School of Medicine, Birmingham, AL; 4Ortho Dermatologics, Bridgewater, NJ; 5Valeant Pharmaceuticals North America LLC, Bridgewater, NJ Winter Clinical Dermatology Conference - Hawaii® • January 12-17, 2018 • Lahaina, HI INTRODUCTION • Brodalumab is a fully human anti–interleukin-17 receptor A (IL-17RA) monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis1 • Efficacy and safety of brodalumab were evaluated in a phase 3, multicenter, randomized, double-blind, placebo-controlled study (AMAGINE-1)1 • There is a well-established association between psoriasis and obesity, with the risk of psoriasis directly related to body mass index (BMI)2,3 – Risk estimate (95% CI) for psoriasis in those with BMI ≥30 kg/m2 was 1.9 (1.2-2.8), as determined from an analysis of an Italian cohort3 • Obese patients with psoriasis often experience decreased efficacy and increased susceptibility to certain side effects of therapeutic agents, making effective treatment in this population challenging2 OBJECTIVE • To evaluate the efficacy and safety of brodalumab in nonobese and obese patients with moderate-to- severe plaque psoriasis METHODS Study design • Efficacy and safety of brodalumab were investigated in a phase 3, multicenter, randomized trial of patients with moderate-to-severe plaque psoriasis (AMAGINE-1) – Patients were randomized to receive brodalumab 210 mg or placebo every 2 weeks (Q2W) for 12 weeks – After 12 weeks, patients were re-randomized to receive brodalumab 210 mg Q2W or placebo for up to 52 weeks • On the basis of BMI, patients were categorized as nonobese (BMI <30 kg/m2) or obese (BMI ≥30 kg/m2) • Comparisons between nonobese and obese patients were made among patients who received continuous treatment with brodalumab 210 mg Q2W through 52 weeks Endpoints/Assessments • Skin clearance was monitored by the static physician’s global assessment (sPGA) and the psoriasis area and severity index (PASI) • Safety was assessed by monitoring exposure-adjusted treatment-emergent adverse event (TEAE) rate per 100 patient-years RESULTS Patient demographics and baseline disease characteristics • Most patients were male, with an approximate mean (standard deviation) age of 45.8 (13.3) years for nonobese patients and 47.0 (12.4) years for obese patients (Table 1) • Of 659 total patients at baseline, 54.6% (n=360) were nonobese and 45.4% (n=299) were obese • Weight and BMI were similar between the placebo and brodalumab groups within the nonobese and obese groups Efficacy • In a post hoc comparison of patients receiving continuous brodalumab 210 mg Q2W, rates of achieving sPGA score of 0 or 1 (sPGA 0/1), 75% improvement in PASI (PASI 75), PASI 90, and PASI 100 were higher among nonobese patients than obese patients at weeks 12 and 52 (Figure) • The percentage of patients achieving PASI 100 increased from week 12 to week 52 in both nonobese and obese patients • Obese patients had a larger increase in response rates of skin clearance as measured by sPGA 0/1, PASI 75, PASI 90, and PASI 100 from week 12 to week 52 compared with nonobese patients • At week 12, 2.3% (3/130), 3.1% (4/130), 1.5% (2/130), and 0.8% (1/130) of nonobese patients receiving placebo achieved sPGA 0/1, PASI 75, PASI 90, and PASI 100, respectively, compared with 0% (0/89), 2.2% (2/89), 0% (0/89), and 0% (0/89) of obese patients (data not shown) – Among nonobese and obese patients randomized to the placebo group after week 12, none achieved sPGA 0/1, PASI 75, PASI 90, or PASI 100 at week 52 (data not shown) Safety • Through 52 weeks, 388.7 TEAEs per 100 patient-years were reported among nonobese patients continuously treated with brodalumab 210 mg Q2W compared with 370.8 TEAEs per 100 patient- years among obese patients (Table 2) Table 1. Baseline Characteristics Table 2. Exposure-Adjusted TEAE Rates Through Week 52 Figure. Nonobese and obese patients who achieved (A) sPGA 0/1, (B) PASI 75, (C) PASI 90, and (D) PASI 100 at weeks 12 and 52. R es po nd er s, % 60 0 40 20 100 80 Week 12 sPGA 0/1 86.8 99 69 63.9 Week 52 86.7 78.9 A R es po nd er s, % 60 0 40 20 100 80 Week 12 PASI 75 90.4 75.9 Week 52 91.1 81.6 B R es po nd er s, % 60 0 40 20 100 80 Week 12 PASI 90 80.7 59.3 Week 52 84.4 71.1 C R es po nd er s, % 60 0 40 20 100 80 Week 12 PASI 100 55.3 27.8 Week 52 80.0 52.6 D Nonobese Obese 39 30 n n n n103 82 41 31 2036306327386492 PASI 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; sPGA 0/1, static physician’s global assessment score of 0 or 1. 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: Van Voorhees – AbbVie, Allergan, Celgene, Dermira, Derm Tech, Novartis, and Valeant Pharmaceuticals North America LLC; Hsu – Abbott, AbbVie, Amgen, Biogen, Centocor Biotech, Dermik, Eli Lilly, Galderma, Genentech, Janssen Biotech, Medicis Pharmaceutical, Novartis, Promius Pharma, Regeneron, Sun Pharmaceutical Industries/Ranbaxy, and Valeant Pharmaceuticals North America LLC; Elewski – AbbVie, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Merck, Novan, Novartis, Pfizer, Sun Pharmaceutical Industries, Valeant Pharmaceuticals North America LLC, and Viamet; Rastogi – Ortho Dermatologics and Valeant Pharmaceuticals North America LLC; and Israel – Valeant Pharmaceuticals North America LLC. References: 1. Papp et al. Br J Dermatol. 2016;175:273-286. 2. Bremmer et al. J Am Acad Dermatol. 2010;63:1058-1069. 3. Naldi et al. J Invest Dermatol. 2005;125:61-67. CONCLUSIONS • Higher rates of skin clearance as assessed by sPGA and PASI were associated with brodalumab 210 mg Q2W in nonobese vs obese patients • Rates of complete skin clearance (PASI 100) increased in both nonobese and obese patients with longer duration of treatment with brodalumab 210 mg Q2W (through 52 weeks) • The increase in response rate of skin clearance from week 12 to week 52 in obese patients was greater than that in nonobese patients, suggesting that response rate can be improved with longer treatment in obese patients Nonobese Obese Placebo (n=130) Brodalumab 210 mg Q2W (n=114) Placebo (n=89) Brodalumab 210 mg Q2W (n=108) Age, mean (SD), y 47.4 (13.7) 44.7 (11.9) 46.1 (12.5) 48.0 (12.3) Sex, n (%) Male Female 101 (77.7) 29 (22.3) 79 (69.3) 35 (30.7) 59 (66.3) 30 (33.7) 82 (75.9) 26 (24.1) Weight, mean (SD), kg 78.6 (12.2) 75.7 (12.5) 107.2 (17.0) 108.0 (20.5) BMI, mean (SD), kg/m2 26.1 (2.6) 25.7 (2.9) 36.4 (5.8) 36.7 (7.2) BMI, body mass index; Q2W, every 2 weeks; SD, standard deviation. n (r) Nonobese (n=181) Obese (n=164) All TEAEs 558 (388.7) 474 (370.8) All SAEs 10 (7.0) 17 (13.3) Deaths 2 (1.4) 1 (0.8) Infections Fungal infections 174 (121.2) 7 (4.9) 149 (116.6) 11 (8.6) n, number of TEAEs; r, exposure-adjusted event rate per 100 patient-years (n/patient-year*100); SAE, serious adverse event; TEAE, treatment- emergent adverse event. © 2017. 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