Efficacy and safety of izokibep in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study.

OBJECTIVES: To evaluate the efficacy and safety of izokibep, a small protein therapeutic designed to inhibit interleukin-17A, in patients with active psoriatic arthritis (PsA) over 46 weeks. METHODS: This phase 2, multicentre, placebo-controlled study randomised adult patients with active PsA 1:1:1 to izokibep 40 mg, izokibep 80 mg, or placebo every 2 weeks for 16 weeks; subsequently, placebo-treated patients switched to izokibep 80 mg. The primary end point was American College of Rheumatology criteria 50 (ACR50) at week 16 for izokibep 80 mg vs placebo. Additional efficacy end points and treatment-emergent adverse events were evaluated through week 16 (placebo-controlled) and week 46. RESULTS: Of 172 patients screened, 135 were randomised to izokibep 40 mg (n = 44), izokibep 80 mg (n = 47), or placebo (n = 44). ACR50 response rates were significantly higher for izokibep 80 mg vs placebo at week 16 (52% vs 13%; 2-sided P = .0006) and week 12 (50% vs 6%; P < .0001); lower rates were observed for izokibep 40 mg (48% and 43% for weeks 16 and 12, respectively). Additional analyses of arthritis, psoriasis, enthesitis, dactylitis, and quality of life outcomes supported the efficacy of izokibep at both doses. Response rates generally continued to increase through week 46 with izokibep 80 mg. Treatment-emergent adverse event rates were generally similar across treatment groups except for injection site reactions. CONCLUSIONS: Izokibep resulted in significant and clinically meaningful improvements over placebo across multiple disease domains, and the originally randomised 80-mg dose showed continued improvements to week 46. There were no unexpected safety risks identified. Izokibep's small size and high potency have the potential for further improved disease control, justifying additional investigation of higher doses.