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

Heijde, Desirée van der; Deodhar, A.; Baraliakos, Xenofon; Brown, Matthew A.; Dobashi, Hiroaki; Dougados, Maxime; Elewaut, Dirk; Ellis, A.M.; Fleurinck, C.; Gaffney, Karl; Gensler, Lianne S.; Haroon, Nigil; Magrey, Marina; Maksymowych, Walter P.; Marten, Alexander; Massow, Ute; Oortgiesen, M.; Poddubnyy, Denis; Rudwaleit, Martín; Shepherd‐Smith, Julie; Tomita, Tadanori; Bosch, Filip Van den; Vaux, T.; Xu, Huji

doi:10.1136/ard-2022-223595

Cited by 45 publications

(63 citation statements)

References 34 publications

(44 reference statements)

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“…The study designs, inclusion and exclusion criteria for the BE MOBILE studies have been described previously (online supplemental figure S1). 22 Patients in BE MOBILE 1 had nr-axSpA, determined by clinical diagnosis and fulfilment of Assessment of SpondyloArthritis International Society (ASAS) classification criteria, but without radiographic sacroiliitis 24. At screening, patients with nr-axSpA were required to have signs of objective inflammation, specifically active sacroiliitis fulfilling ASAS criteria25 and/or elevated C-reactive protein (CRP) ≥6.0 mg/L.…”

Section: Methodsmentioning

confidence: 99%

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Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

Baraliakos,

Deodhar,

van der Heijde

et al. 2023

Ann Rheum Dis

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ObjectivesBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52.MethodsBE MOBILE 1 (nr-axSpA;NCT03928704) and BE MOBILE 2 (r-axSpA;NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks.ResultsImprovements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%).ConclusionsAt Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ.Trial registration numberNCT03928704;NCT03928743.

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Section: Methodsmentioning

confidence: 99%

“…In the parallel phase 3 studies BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (r-axSpA), patients receiving subcutaneous 160 mg BKZ Q4W achieved the primary and all ranked secondary endpoints at Week 16 22. At Week 24, no new safety signals were observed with BKZ treatment, compared with the 3-year phase 2b BE AGILE study of BKZ in r-axSpA 23.…”

Section: Introductionmentioning

confidence: 99%

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

Baraliakos,

Deodhar,

van der Heijde

et al. 2023

Ann Rheum Dis

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“…Indeed, IL-17F levels are higher in AS patient serum; this cytokine may stimulate in vitro osteogenic differentiation and bone formation, acting synergistically with IL-17A in new bone formation [ 201 ]. On this basis, the monoclonal antibody neutralizing both IL-17A/F, bimekizumab, was shown to be effective in phase II and III clinical trials [ 202 , 203 , 204 ]. Figure 3 shows the main molecular targets in axial-SpA.…”

Section: Therapeutic Targets In Axial-spamentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

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“…In contrast, tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab, golimumab) are highly effective in axSpA [41] and a similar effect is assumed also in axial PsA, although there are no studies specifically addressing the latter patient population. Similarly, interleukin-17 (IL-17) inhibitors (bimekizumaban IL-17A and F inhibitor, ixekizumab and secukinumabboth IL-17A inhibitors) showed efficacy in Phase III trials in axSpA [41,42] and are also considered to be effective in axial PsA. However, secukinumab is, as of today, the only bDMARD, which has been investigated on the target patient population with axial PsA.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Managing Psoriatic Arthritis Patients Presenting with Axial Symptoms

Poddubnyy

2023

Drugs

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Axial symptoms (i.e., back pain) are common in the general population. At the same time 25-70% of patients with psoriatic arthritis (PsA) exhibit signs of inflammatory axial involvement (axial PsA). The presence of unexplained chronic (duration ≥ 3 months) back pain in a patient with psoriasis or PsA should trigger evaluation of the presence of axial involvement. Evaluation of axial involvement normally involves imaging of the axial skeleton (sacroiliac joints and/or spine) in addition to clinical and laboratory evaluation. Symptomatic patients with confirmed axial PsA are treated with a combination of nonpharmacologic and pharmacologic methods including the use of non-steroidal anti-inflammatory drugs, tumour necrosis factor, interleukin 17, and Janus kinase inhibitors. Interleukin 23 blockade might also be effective in the axial domain of PsA; a dedicated clinical study is ongoing at present. Safety considerations, patient preference, as well as the presence of other disease manifestations (especially of extra-musculoskeletal manifestations-clinically relevant psoriasis, acute anterior uveitis, inflammatory bowel disease), define the choice of a specific drug or drug class. Key PointsAxial symptoms (first of all, chronic back pain) in patients with psoriasis/psoriatic arthritis, especially if started at young age should raise a suspicion of the presence of axial involvement.The diagnostic evaluation of axial symptoms should normally include imaging for the detection of active inflammatory and structural changes indicative of axial involvement.Symptomatic patients with confirmed axial involvement should be treated with a combination of nonpharmacologic and pharmacologic methods including the use of non-steroidal anti-inflammatory drugs, tumour necrosis factor, interleukin 17, and Janus kinase inhibitors.

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

Cited by 45 publications

References 34 publications

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

Uncovering the Underworld of Axial Spondyloarthritis

Managing Psoriatic Arthritis Patients Presenting with Axial Symptoms

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