How New Medications are Reframing Imaging Abnormalities in axSpA Save

Bimekizumab (BKZ), a monoclonal antibody that selectively targets both IL-17A and IL-17F, was evaluated in the BE MOBILE 1 (non-radiographic axSpA) and BE MOBILE 2 (radiographic axSpA) trials and found to yield significant clinical benefit – around 60% of patients in both trials achieved an Assessment in SpondyloArthritis international Society (ASAS)40 response rate, with improvement in all specific ASAS domains.

Here we review three abstracts presented at ACR24 that shed potential insight into the disease-modifying role of BKZ, and other targeted agents, in axSpA using imaging findings during disease treatment.

1. Does BKZ improve SI joint inflammation and structural change on serial MRI?

Maksymowych et al. performed MRI sub-studies in BE MOBILE 1 and BE MOBILE 2 patients measuring MRI activity at baseline, at week 16, and at week 52 (Abstract 1757). Activity was evaluated using the Spondyloarthritis research consortium of Canada (SPARCC) SI joint inflammation score and SPARCC SI joint structural scores, measured by two, blinded, independent readers. Only patients with MRI assessment at all 3 timepoints and baseline elevated inflammation scores were included.

Average baseline scores were comparable between groups however the BKZ treated patients, in both the radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA), achieved greater proportions of MRI remission at week 16 (66% BKZ vs. 28% PBO in nr-axSpA and 58% vs. 16% in r-axSpA). At week 52 patients in the placebo group who crossed over to BKZ use at 16 weeks also achieved significant improvements in MRI disease activity and the original BKZ groups continued to see improvement. Structural lesions, such as erosions, were reduced with BKZ treatment.

2. Does BKZ prevent radiographic progression in patients with r-axSpA?

Baraliakos et al. used open label extension of the BE MOBILE 2 study to help address this question, following patients with r-AxSpA through two years on BKZ treatment (abstract 1758). Using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), the group found minimal structural progression among treated patients. 

The majority of participants (85%) exhibited no significant radiographic changes, with 92% classified as non-progressors when using a stricter mSASSS threshold. By week 104, 21% of patients with baseline syndesmophytes and 1.5% of patients without baseline syndesmophytes developed new lesions.

Predictors of progression included baseline syndesmophytes, HLA-B27 positivity, and elevated inflammatory markers.

3. Are there other predictors of radiographic progression in r-AxSpA?

Poddubnyy et al. performed a post-hoc analysis of the SURPASS trial, which randomized active r-axSpA patients to secukinumab (an IL-17A inhibitor, 150mg or 300mg dosing) or adalimumab biosimilar (a TNF inhibitor) in biologic-naïve r-axSpA patients over two years (abstract 1759).

Findings revealed similar rates of new syndesmophyte formation across treatment groups (14.9%–18.2%), with high baseline inflammation (elevated CRP, higher ASDAS, higher spinal MRI bone marrow edema scores) and pre-existing syndesmophytes identified as key risk factors for progression. The mean spinal bone marrow edema was higher in faster progressors and although generally decreased over time, remained higher at week 104 compared to slow- or non-progressors.

These studies highlight the efficacy of the novel agent BKZ on reducing imaging progression, by both x-ray and MRI, in Ax-SpA. They also identify that regardless of TNF or IL-17 targeting, patients with high baseline inflammatory disease and syndesmophyte burden at most at risk for imaging progression.