Long-term Efficacy and Safety of Brodalumab in Patients With or Without History of Psoriatic Arthritis: Analysis of Two Phase 3 Psoriasis Studies Alice Gottlieb,1 Alan Menter,2 Paul Yamauchi,3 Craig Teller,4 George Han,1 Radhakrishnan Pillai,5 Tina Lin,6 Abby Jacobson6 1Icahn School of Medicine at Mount Sinai, New York, NY; 2Baylor Scott & White, Dallas, TX; 3Dermatology Institute & Skin Care Center, Santa Monica, CA; 4Bellaire Dermatology, Bellaire, TX; 5Bausch Health Americas*, Petaluma, CA; 6Ortho Dermatologics*, Bridgewater, NJ *Bausch Health Americas and Ortho Dermatologics are divisions or affiliates of Bausch Health Companies, Inc. 39th Annual Fall Clinical Dermatology Conference® for Dermatologists • October 17-20, 2019 • Las Vegas, NV INTRODUCTION • Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis1 • Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis2 OBJECTIVE • To evaluate the efficacy and safety of brodalumab in a post hoc analysis of two phase 3, multicenter, randomized trials of brodalumab in patients with moderate-to-severe plaque psoriasis (AMAGINE-2/-3; Figure 1) with or without a history of psoriatic arthritis3 METHODS • In AMAGINE-2/-3, 3625 patients received brodalumab, of whom 703 (19.4%) had a self-reported history of PsA at baseline and 2922 (80.6%) did not • Patients were initially randomized to brodalumab 140 or 210 mg every 2 weeks (Q2W), ustekinumab, or placebo3 • At week 52, all patients entered a long-term extension and received brodalumab4 • This analysis included patients who received any dose of brodalumab through week 120 and patients receiving brodalumab 210 mg Q2W after ustekinumab • Skin clearance efficacy was measured by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI) • Psoriasis symptom inventory (PSI) and dermatology life quality index (DLQI) were also used – The PSI measures the severity of 8 signs and symptoms of psoriasis (itch, redness, scaling, burning, stinging, cracking, flaking, and pain) each scored on a scale of 0 (not at all severe) to 4 (very severe), with a total score of up to 32 – A PSI responder was defined as having a total score ≤8 with no item scores >1 • Safety was summarized via exposure-adjusted rates of treatment- emergent adverse events (TEAEs) RESULTS Efficacy • In an observed analysis at week 120, 74.8% of patients receiving any dose of brodalumab with a history of PsA (n=329) and 79.1% without a history of PsA (n=1501) had an sPGA score of 0 or 1 • 75% improvement in PASI from baseline (PASI 75; Figure 2A), PASI 90 (Figure 2B), and PASI 100 (Figure 2C) responses were maintained from week 52 through 120 in those receiving any dose of brodalumab with and without a history of PsA – At week 120, PASI 75 rates were 87.2% and 90.0%, PASI 90 rates were 76.0% and 78.7%, and PASI 100 rates were 57.8% and 58.0% in patients with and without a history of PsA, respectively • Skin clearance was also maintained at similar levels in patients with (n=105) and without (n=462) a history of PsA who received brodalumab 210 mg Q2W after ustekinumab – At week 120, PASI 75 rates were 86.2% and 91.3%, PASI 90 rates were 72.4% and 83.1%, and PASI 100 rates were 60.3% and 63.2% in patients with and without a history of PsA, respectively PSI and DLQI responses • The rates of PSI and DLQI score of 0 or 1 responses were robust among brodalumab-treated patients at week 52 (the last observation time point) – The rates of PSI response were 73.5% and 79.3% in patients with and with- out a history of PsA, respectively (Figure 3A) – The rates of DLQI score of 0 or 1 were 67.2% and 72.4% in patients with and without a history of PsA, respectively (Figure 3B) Safety • Across all study years, TEAE rates in patients receiving any dose of brodalumab with and without a history of PsA were 331.9 and 292.8 per 100 patient-years, respectively (Table 1) © 2019. All Rights Reserved. ► ► ► ► Day 1 Week 12 Week 16 Week 52 ► Week 120 Ustekinumab Brodalumab 210 mg Q2W Brodalumab 210 mg Q2W Ustekin umabPlacebo Ustekin umabUstekinumab Brodalumab 210 mg Q2W Induction Maintenance Long-term extension Week 16 inadequate responders Brodalumab 210 mg Q2W Brodalumab 140 mg Q2W Brodalumab 140 mg Q4W Brodalumab 140 mg Q8W Brodalumab 140 mg Q2W R 2:2:2:1 R 2:2:1:1 Brodalumab 210 mg Q2W (rescue) Figure 1. AMAGINE-2/-3 study design. R, randomization; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks. 50.5 73.5 55.5 79.3 0 20 40 60 80 100 Week 12 Week 52 R es po nd er s, % PSI response 44.7 67.2 46.5 72.4 0 20 40 60 80 100 Week 12 Week 52 DLQI 0/1 History of PsA No history of PsA 648 4952658 2098N1= 662 5492778 2354 A B Figure 3. PSI and DLQI 0/1 response rates in brodalumab-treated patients by history of PsA subgroups. Observed data analysis. Error bars are the 95% confidence interval. DLQI 0/1, dermatology life quality index score of 0 or 1; PsA, psoriatic arthritis; PSI, psoriasis symptom inventory. Table 1. Exposure-Adjusted Rates of TEAEs in Patients Who Received Any Dose of Brodalumab History of PsA (N=703, 1219.2 PY) No history of PsA (N=2922, 5312.3 PY) All TEAEs, n (r) 4046 (331.9) 15,556 (292.8) Grade ≥2 2202 (180.6) 8194 (154.2) Grade ≥3 181 (14.8) 639 (12.0) Serious AEs, n (r) 117 (9.6) 364 (6.9) Fatal AEs, n (r)a 1 (0.1) 2 (0.0) Observed data analysis. AE, adverse event; CI, confidence interval; n, number of adverse events; N, number of patients; PsA, psoriatic arthritis; PY, total patient-years of exposure through the end of the study; r, exposure-adjusted event rate per 100 patient-years; TEAE, treatment-emergent AE. aThe 3 fatal AEs were 1 sudden death (cause undetermined), 1 cardiac arrest (267 days on brodalumab; event occurred 7 days after last dose), and 1 accidental death (motor vehicle accident). Weeks 12 24 36 52 72 84 96 108 1200 Weeks 12 24 36 52 72 84 96 108 1200 91.1 91.9 History of PsA No history of PsA History of PsA No history of PsA History of PsA No history of PsA N1= 703 677 651 623 572 569 552 538 463 329 N1= 2922 2868 2702 2670 2442 25 31 2482 2416 2135 1501 PASI 75 90.0 87.2 A 79.4 76.0 78.7 78.7 N1= 703 677 651 623 572 569 552 538 463 329 N1= 2922 2868 2702 2670 2442 2531 2482 2416 2135 1501 PASI 90B 54.1 N1= 703 677 651 623 572 569 552 538 463 329 N1= 2922 2868 2702 2670 2442 2531 2482 2416 2135 1501 PASI 100 Weeks 12 24 36 52 72 84 96 108 1200 58.0 57.8 54.2 C 0 20 40 60 80 100 R es po nd er s, % 0 20 40 60 80 100 R es po nd er s, % 0 20 40 60 80 100 R es po nd er s, % Figure 2. PASI 75 (A), PASI 90 (B), and PASI 100 (C) responses through week 120 in patients who received ≥1 dose of brodalumab by history of PsA subgroups. Observed data analysis. Error bars are the 95% confidence interval. N1, number of patients who had a valid measurement at the specified week; PASI 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; PsA, psoriatic arthritis; Q2W, every 2 weeks. CONCLUSION • Skin clearance rates were maintained through week 120 in patients regardless of PsA history • The data presented here suggest that brodalumab is efficacious and well tolerated in patients with and without history of PsA Acknowledgments: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC. References: 1. Gottlieb et al. J Am Acad Dermatol. 2008;58:851-864. 2. Siliq [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America, LLC; 2017. 3. Lebwohl et al. N Engl J Med. 2015;373:1318-1328. 4. Menter et al. Poster presented at the 2017 Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV.