Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

Désirée van der Heijde; Atul Deodhar; Xenofon Baraliakos; Matthew A Brown; Hiroaki Dobashi; Maxime Dougados; Dirk Elewaut; Alicia M Ellis; Carmen Fleurinck; Karl Gaffney; Lianne S Gensler; Nigil Haroon; Marina Magrey; Walter P Maksymowych; Alexander Marten; Ute Massow; Marga Oortgiesen; Denis Poddubnyy; Martin Rudwaleit; Julie Shepherd-Smith; Tetsuya Tomita; Filip Van den Bosch; Thomas Vaux; Huji Xu

doi:10.1136/ard-2022-223595

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

Ann Rheum Dis. 2023 Apr;82(4):515-526. doi: 10.1136/ard-2022-223595. Epub 2023 Jan 17.

Authors

Désirée van der Heijde¹, Atul Deodhar², Xenofon Baraliakos³, Matthew A Brown⁴, Hiroaki Dobashi⁵, Maxime Dougados⁶, Dirk Elewaut^{7

8}, Alicia M Ellis⁹, Carmen Fleurinck¹⁰, Karl Gaffney¹¹, Lianne S Gensler¹², Nigil Haroon¹³, Marina Magrey¹⁴, Walter P Maksymowych¹⁵, Alexander Marten¹⁶, Ute Massow¹⁶, Marga Oortgiesen⁹, Denis Poddubnyy¹⁷, Martin Rudwaleit¹⁸, Julie Shepherd-Smith¹⁹, Tetsuya Tomita²⁰, Filip Van den Bosch²¹, Thomas Vaux¹⁹, Huji Xu²²

Affiliations

¹ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
² Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA deodhara@ohsu.edu.
³ Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Herne, Germany.
⁴ Genomics England, London, UK.
⁵ Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
⁶ Department of Rheumatology, Hôpital Cochin, University Paris Cité, Paris, France.
⁷ Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
⁸ VIB Center for Inflammation Research, Ghent University, Ghent, Belgium.
⁹ UCB Pharma, Raleigh, North Carolina, USA.
¹⁰ UCB Pharma, Brussels, Belgium.
¹¹ Norfolk and Norwich University Hospital NHS Trust, Norfolk, UK.
¹² Department of Medicine/Rheumatology, University of California, San Francisco, California, USA.
¹³ University Health Network, Schroeder Arthritis Institute, Department of Medicine/Rheumatology, University of Toronto, Toronto, Ontario, Canada.
¹⁴ University Hospitals, Case Western Reserve University, Cleveland, Ohio, USA.
¹⁵ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
¹⁶ UCB Pharma, Monheim, Germany.
¹⁷ Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁸ Klinikum Bielefeld, University of Bielefeld, Bielefeld, Germany.
¹⁹ UCB Pharma, Slough, UK.
²⁰ Graduate School of Health Science, Morinomiya University of Medical Sciences, Osaka City, Osaka, Japan.
²¹ Department of Internal Medicine and Pediatrics, Ghent University and VIB Center for Inflammation Research, Ghent, Belgium.
²² Affiliated to Second Military Medical University, Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Shanghai, China.

Abstract

Objectives: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.

Methods: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24.

Results: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low.

Conclusions: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Keywords: Autoimmune Diseases; Biological Therapy; Cytokines; Inflammation; Spondylitis, Ankylosing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Double-Blind Method
Humans
Interleukin-17
Non-Radiographic Axial Spondyloarthritis*
Randomized Controlled Trials as Topic
Spondylarthritis* / drug therapy
Spondylitis, Ankylosing* / drug therapy
Treatment Outcome

Substances

bimekizumab
Interleukin-17