SAT0417 TILDRAKIZUMAB EFFICACY ON PSORIASIS IN PATIENTS WITH PSORIATIC ARTHRITIS—A 52-WEEK ANALYSIS FROM A PHASE 2 STUDY
Authors: A. B. Gottlieb, C. T. Ritchlin, R. C. Chou, A. M. Mendelsohn, S. Rozzo, L. Espinoza
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tildrakizumab (TIL)—a high-affinity anti–interleukin-23p19 monoclonal antibody—is approved in the US, EU, and Australia to treat moderate to severe plaque psoriasis. 1 A randomised, double-blind, multidose, placebo-controlled, phase 2b study ( NCT02980692 ) evaluating the efficacy and safety of TIL for the treatment of psoriatic arthritis (PsA) was recently completed. Objectives: To evaluate the proportion with 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI 75/90/100) among patients (pts) with PsA and measurable psoriasis (≥3% of the body surface area [BSA] affected at baseline) over 52 weeks of treatment. Methods: Pts ≥18 years old with PsA 2 and ≥3 tender and ≥3 swollen joints, stratified by prior anti-TNF use and baseline body weight (≤90 kg and &gt;90 kg), were randomised 1:1:1:1:1 to receive TIL 200 mg every 4 weeks (Q4W) to week 52 (W52), TIL 200 mg every 12 weeks (Q12W) to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W to W24→TIL 200 mg Q12W to W52, or placebo (PBO) Q4W to W24→TIL 200 mg Q12W to W52. PASI 75/90/100 were prespecified endpoints and were assessed by an independent assessor. Pts who received ≥1 dose of study drug were analysed. Safety assessments included treatment-emergent adverse event (TEAE) monitoring. Results: Overall, 391/500 pts screened met inclusion criteria; 235 (60.1%) had ≥3% BSA involvement at baseline (41–55/treatment arm). Demographics and baseline disease characteristics were generally consistent across treatment arms. Mean (standard deviation [SD]) age was 48.8 (12.6) years, average body mass index was 29.7, 96.7% of pts were White, and 23.3% were anti–tumour necrosis factor (TNF)-experienced. At baseline, the mean (SD) PASI score was 6.8 (8.2) and mean (SD) BSA affected was 10.5% (14.3%) overall. Among pts with baseline BSA ≥3%, TIL treatment significantly increased the proportion of PASI 75/90/100 responders vs PBO at W24; the proportion of responders continued to increase thereafter and was sustained through W52 ( Figure ). Similarly, in pts switching from PBO → TIL 200 mg Q12W or escalating from TIL 20 → 200 mg Q12W after W24, PASI 75/90/100 response rates increased through W36 and remained stable through W52. From W0 → W24/W25 → W52, 50.4%/39.9% pts experienced a TEAE. The most frequent TEAEs were nasopharyngitis (pooled TIL arms 5.4%/4.2% vs PBO 6.3%/3.8%) and upper respiratory tract infection (pooled TIL arms 3.8%/4.2% vs PBO 1.3%/0.0%). One pt (0.3%) discontinued before 24 weeks due to hypertension. There were no deaths or major adverse cardiac events during W0 → W24 or W25 → W52. Conclusion: PASI75/90/100 response rates progressively improved with treatment; PASI 75 responses were significantly improved vs placebo as early as W4 (TIL 200 mg Q12W), and all response rates were significantly improved vs placebo at W24. Response rates continued to improve through W36 and were sustained through W52. These results demonstrate TIL significantly reduced psoriasis disease activity and was generally well tolerated in a mixed population of anti–TNF-naïve and -experienced patients with PsA and BSA ≥3% through W52. References: [1]Reich K, et al. Lancet. 2017;390(10091):276−88. [2]Taylor W, et al. Arthritis Rheum . 2006; 54(8):2665–73. Disclosure of Interests: Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Luis Espinoza: None declared