LB0001 Dual neutralisation of il-17a and il-17f with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study
Authors: D. van der Heijde, L.S. Gensler, A. Deodhar, X. Baraliakos, D. Poddubnyy, M.K. Farmer, D. Baeten, T. Kumke, M. Oortgiesen, M. Dougados
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Dual neutralisation of IL-17F, in addition to IL-17A, reduces inflammation<sup>1</sup> to a greater extent than inhibition of IL-17A alone in disease–relevant cell models. Bimekizumab, a monoclonal antibody that potently and selectively neutralises both IL-17A and IL-17F, provided rapid and substantial clinical improvements in studies evaluating patients with psoriasis<sup>2</sup> and psoriatic arthritis.<sup>1</sup> <h3>Objectives</h3> Assess 12 week efficacy and safety of bimekizumab in patients with active AS; the primary objective was to assess the ASAS40 dose-response relationship at Week 12. <h3>Methods</h3> In this ongoing 48 week study (NCT02963506: double blind to Week 12 then dose blind to Week 48), 303 patients with active (BASDAI ≥4; spinal pain ≥4 [0–10 numerical rating scale]) AS, fulfilling the modified New York criteria, were randomised 1:1:1:1:1 to receive subcutaneous bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo Q4W, for 12 weeks. Prior exposure to 1 anti-TNF therapy was permitted. The primary endpoint was ASAS40 response rate at Week 12. Secondary endpoints (ASAS20 and ASAS5/6 response rate and change from baseline in BASDAI and ASDAS-CRP at Week 12) and safety were also assessed. <h3>Results</h3> Overall, 297 (98.0%) patients completed the 12 week double-blind period. The majority of patients were male (84.5%) with a mean (SD) age of 42.2 (11.8) and median (min, max) symptom duration of 13.3 (0.3, 48.2) years; baseline characteristics were similar among treatment groups (median [min, max] hs-CRP: 12.1 [0.3, 130.6] mg/L; mean [SD] BASDAI: 6.5 [1.4]; ASDAS-CRP: 3.9 [0.8]; prior anti-TNF exposure: 11.2%). At Week 12, there was a significant (p&lt;0.001) dose-response for ASAS40. A greater percentage of bimekizumab-treated patients achieved ASAS40 (primary endpoint) than placebo (Figure: p&lt;0.05, all doses). More patients receiving bimekizumab than placebo also achieved ASAS20 (figure 1; p&lt;0.05, 64 mg–320 mg doses) and ASAS5/6 (16mg: 29.5%; 64 mg: 39.3%; 160 mg: 50.0%; 320 mg: 52.5%; placebo: 5.0%; p<i>&lt;</i>0.05, all comparisons). Compared with placebo, greater reductions from baseline were achieved with bimekizumab for both BASDAI (figure 1) and ASDAS-CRP (LS mean [SE] change from baseline: 16 mg: −1.0 [0.15]; 64 mg: −1.6 [0.15]; 160 mg: −1.4 [0.16]; 320 mg: −1.5 [0.16]; placebo: −0.4 [0.16]; p&lt;0.001, all doses). The overall incidence of TEAEs was 86/243 (35.4%) for bimekizumab-treated patients versus 22/60 (36.7%) for placebo. No unexpected safety risks were observed; the most frequently reported events were nasopharyngitis and headache. <h3>Conclusions</h3> The primary and key secondary objectives were achieved; dual neutralisation of IL-17A and IL-17F with bimekizumab provided clinically meaningful improvements in disease outcome measures. No new safety signals were observed versus previous studies.<sup>1 2</sup> <h3>References</h3> [1] Glatt. Ann Rheum Dis2018;77:523–532. [2] Glatt. Br J Clin Pharmacol2017;83:991–1001. <h3>Acknowledgements</h3> Study funded by UCB Pharma. The authors acknowledge K Alexander of iMed Comms, an Ashfield Company, for medical writing support funded by UCB Pharma in accordance with GPP3. <h3>Disclosure of Interest</h3> D. van der Heijde Consultant for: AbbVie; Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Director of Imaging Rheumatology BV, L. S. Gensler Grant/research support from: AbbVie, Amgen, UCB, Consultant for: Novartis, Lilly, Janssen, A. Deodhar Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, X. Baraliakos Grant/research support from: Abbvie, Pfizer, MSD, UCB, Novartis, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB, D. Poddubnyy Grant/research support from: Abbvie, MSD, Novartis, Consultant for: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, UCB, M. K. Farmer Employee of: UCB Pharma, D. Baeten Employee of: UCB Pharma, T. Kumke Employee of: UCB Pharma, M. Oortgiesen Shareholder of: UCB Pharma, Employee of: UCB Pharma, M. Dougados Grant/research support from: UCB, Lilly, Pfizer, AbbVie, Merck, Consultant for: UCB, Lilly, Pfizer, AbbVie, Merck