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
Authors: Christopher T. Ritchlin, Arthur Kavanaugh, Joseph F. Merola, Georg Schett, Jose U. Scher, Richard B. Warren, Deepak Assudani, Thomas Kumke, Barbara Ink, Iain Mcinnes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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&lt;0.05) dose-response at Week 12 for ACR50 response rates. At Week 12, significantly more pts receiving BKZ versus PBO achieved ACR50 (primary endpoint: 16–160mg [LD] doses), ACR20 and PASI90 (in those pts with baseline body surface area ≥3%; 160–320mg doses) (table). ACR20/50/70, PASI75/90/100, MDA and resolution of enthesitis response rates increased between Week 12 and Week 24 in those continuing on their initial BKZ dose; Week 24 responses were maintained through the study; responses were similar across the three highest dose groups at Week 48 (PASI100 analyses were <i>post hoc</i>). Rapid improvements were observed across all response criteria in pts re–allocated to BKZ 160 or 320mg (table). BKZ-treated pts naïve to TNFi achieved ACR20/50 and PASI90/100 at comparable rates to the overall population at Week 12 and 48. There was no apparent relationship between dose and TEAEs. Serious AEs were reported by 9/206 (4.4%) pts up to Week 48 (8/206 [3.9%] patients were receiving BKZ). The most common TEAE up to Week 48 was nasopharyngitis 25/206 [12.1%]). Oral candidiasis was reported at Week 48 by 10/206 (4.9%) pts (all cases during BKZ treatment). No deaths, or cases of IBD or MACE were reported. <h3>Conclusion</h3> 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. <h3>Acknowledgement</h3> Funded by UCB Pharma. <h3>Disclosure of Interests</h3> 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