OP0108 DUAL NEUTRALISATION OF IL-17A AND IL-17F WITH BIMEKIZUMAB IN PATIENTS WITH ACTIVE PSA: OVERALL AND TNF-INHIBITOR-NAÏVE POPULATION RESULTS FROM A 48-WEEK PHASE 2B RANDOMISED STUDY

Abstract

Background IL-17F shares structural homology and pro-inflammatory function with IL–17A. Preclinical and early clinical data support neutralisation of IL-17F, in addition to IL–17A, as a novel targeting approach in psoriatic disease. Objectives The objective of this Phase 2b study (NCT02969525) was to assess the dose response, long-term efficacy and safety of bimekizumab (BKZ), a mAb that potently and selectively neutralises IL-17A and IL-17F, over 48 weeks in patients (pts) with active PsA. Methods 206 pts with active PsA, ≥3/76 swollen joint count, ≥3/78 tender joint count and CASPAR score ≥3, were randomised (1:1:1:1:1) to receive subcutaneous BKZ 16mg, 160mg, 160mg with 320mg loading dose (160mg [LD]), 320mg or placebo (PBO) Q4W, for 12 weeks (double-blind period). After Week 12, pts receiving PBO or BKZ 16mg were re-randomised (1:1) to BKZ 160mg or 320mg; all other pts continued on their initial dose (dose-blind period). The primary endpoint was ACR50 response at Week 12. Results 203/206 and 189/206 pts completed the double- and dose-blind periods, respectively. Overall, demographics and baseline disease characteristics were balanced across groups. 19% of pts had prior exposure to TNF inhibitors (TNFi). There was a statistically significant (p Conclusion Dual neutralisation of IL-17A and IL-17F with BKZ provided substantial improvements in both musculoskeletal and skin outcomes; response rates increased after Week 12 (primary analysis) and were sustained from Week 24 to 48, with a safety profile consistent with previous BKZ studies. These data provide further support that neutralising IL–17F in addition to IL-17A with BKZ is a promising therapeutic approach in pts with active PsA. Acknowledgement Funded by UCB Pharma. Disclosure of Interests Christopher T. Ritchlin Grant/research support from: AbbVie, Amgen, UCB Pharma, Consultant for: AbbVie, Amgen, Lilly, Novartis, Pfizer, UCB Pharma, Arthur Kavanaugh Grant/research support from: UCB Pharma, Joseph F. Merola Consultant for: Biogen IDEC, Abbvie, Amgen, Eli Lilly and Company, Novartis, Pfizer, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, Merck, and GSK, Georg Schett: None declared, Jose U. Scher Consultant for: BMS, Janssen, Novartis, UCB Pharma, Richard B. Warren Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, LEO, Novartis, Pfizer, UCB Pharma, Consultant for: AbbVie, Almirall, Amgen, Boehringer-Ingleheim, Celgene, Janssen, LEO, Lilly, Novartis, Pfizer, Sanofi, UCB, Xenoport, Deepak Assudani Shareholder of: UCB Pharma, Employee of: UCB Pharma, Thomas Kumke Employee of: UCB Pharma, Barbara Ink Shareholder of: GSK, UCB Pharma, Employee of: UCB Pharma, Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma