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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
  1. D. van der Heijde1,
  2. L.S. Gensler2,
  3. A. Deodhar3,
  4. X. Baraliakos4,
  5. D. Poddubnyy5,
  6. M.K. Farmer6,
  7. D. Baeten7,
  8. T. Kumke8,
  9. M. Oortgiesen6,
  10. M. Dougados9
  1. 1Leiden University Medical Center, Leiden, Netherlands
  2. 2University of California, San Francisco
  3. 3Oregon Health and Science University, Portland, USA
  4. 4Ruhr-University Bochum, Herne
  5. 5Charité – Universitätsmedizin Berlin, German Rheumatism Research Centre, Berlin, Germany
  6. 6UCB Pharma, Raleigh, USA
  7. 7UCB Pharma, Brussels, Belgium
  8. 8UCB Pharma, Monheim, Germany
  9. 9Cochin Hospital, Paris, France

Abstract

Background Dual neutralisation of IL-17F, in addition to IL-17A, reduces inflammation1 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 psoriasis2 and psoriatic arthritis.1

Objectives 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.

Abstract LB0001 – Figure 1 A) non-responder imputation, full analysis set; B) observed data, full analysis set

Methods 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.

Results 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<0.001) dose-response for ASAS40. A greater percentage of bimekizumab-treated patients achieved ASAS40 (primary endpoint) than placebo (Figure: p<0.05, all doses). More patients receiving bimekizumab than placebo also achieved ASAS20 (figure 1; p<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<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<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.

Conclusions 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.1 2

References [1] Glatt. Ann Rheum Dis2018;77:523–532.

[2] Glatt. Br J Clin Pharmacol2017;83:991–1001.

Acknowledgements 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.

Disclosure of Interest 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

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