Dual Inhibition of IL-17A/IL-17F Across the Spectrum of Axial Spondyloarthritis

Comprehensive axSpA

AxSpA is a chronic immune-mediated inflammatory disease with various manifestations, especially in the sacroiliac joints and spine, but also in the periphery and extramusculoskeletal areas. The spectrum of axSpA includes both patients with definitive structural damage to the sacroiliac joint visible on an X-ray, known as the radiographic form (r-axSpA), and patients without apparent structural damage (non-radiographic form of the disease – nr-axSpA).

The burden caused by axSpA significantly and permanently affects the lives of patients. Many of them also experience treatment failure, an inability to achieve therapeutic goals, or persistent residual symptoms. For these reasons, new therapeutic options and drugs with new mechanisms of action are being sought.

Methodology and course of BE MOBILE 1 and 2 studies

The key mediators of inflammation in axSpA are IL-17A and IL-17F. In the phase IIb study BE ACTIVE and its open-label extension in patients with active r-axSpA, the use of bimekizumab at a dose of 160 mg every 4 weeks led to rapid disease control compared to placebo, with efficacy maintained for up to 3 years.

BE MOBILE 1 and BE MOBILE 2 are parallel 52-week randomized double-blind phase III studies: BE MOBILE 1 focused on the safety and efficacy of treating patients with nr-axSpA, and BE MOBILE 2 focused on patients with r-axSpA. The studies involved patients with active disease who had failed previous treatment with at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) or had contraindications to them, or did not tolerate them.

Patients in each study were randomized into 2 arms (254 patients with nr-axSpA in a 1:1 ratio and 332 with r-axSpA in a 2:1 ratio) to receive bimekizumab 160 mg every 4 weeks or placebo. From week 16, patients in the placebo arm also received bimekizumab 160 mg every 4 weeks.

The primary goal of the studies was at least a 40% improvement in assessment according to the criteria of the International Society for Spondyloarthritis (ASAS40). The target indicators were assessed at week 16.

Findings

Efficacy

At week 16, ASAS40 was achieved by 47.7% of patients with nr-axSpA treated with bimekizumab vs. 21.4% in the placebo group. In patients with r-axSpA, this ratio was 44.8 vs. 22.5% (p < 0.001). ASAS40 responses were similar in patients who had not previously used tumor necrosis factor inhibitors (TNFi) and in those who had used TNFi but did not show an adequate response.

Improvements were also observed in the Ankylosing Spondylitis Disease Activity Score (ASDAS) and objective indicators of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine.

Administration of active treatment led to significant improvements in ASAS responses, physical function, pain reduction, quality of life, and spinal mobility compared to placebo, in both nr-axSpA and r-axSpA patients. Efficacy was not affected by prior exposure to TNFi.

Safety

The drug was generally well-tolerated in patients with nr-axSpA and r-axSpA, and no new safety signals were observed.

The most common adverse events related to bimekizumab treatment (occurring in > 3% of participants) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhea, headache, and oral candidiasis. Fungal infections (all localized) were observed more frequently in patients receiving bimekizumab. No serious cardiovascular events (MACE) or active tuberculosis were reported. The incidence of uveitis and inflammatory bowel disease was low.

Conclusion

The first two phase III studies evaluating the efficacy and safety of dual inhibition of IL-17F and IL-17A with bimekizumab in the full spectrum of patients with axSpA show that bimekizumab administration led to rapid and clinically relevant alleviation of disease symptoms compared to placebo and was well-tolerated. The researchers conclude that bimekizumab may offer an effective treatment option with a new mechanism of action for patients with axSpA.

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Source: van der Heijde D., Deodhar A., Baraliakos X. et al. Efficacy and safety of bimekizumab in axial spondyloarthritis: Results of two parallel phase 3 randomised controlled trials. Ann Rheum Dis 2023 Jan 17; 82 (4): 515–526, doi: 10.1136/ard-2022-223595.