Objective: To assess the effect of filgotinib, which preferentially inhibits Janus kinase 1 (JAK1), on magnetic resonance imaging (MRI) measures of structural change in the sacroiliac (SI) joint in patients with active ankylosing spondylitis (AS) in the TORTUGA trial.
Methods: Adults with active AS and inadequate response/intolerance to ≥ 2 non-steroidal anti-inflammatory drugs were randomized (1:1) to filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post-hoc analysis, T1-weighted MRI scans of the SI joint were evaluated by two independent readers using Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Structural Score (SSS) definitions for erosion, backfill, fat metaplasia and ankylosis. Correlations between SPARCC SSS and improvement in clinical outcomes were also assessed.
Results: . MRI scans from 87 patients (48 filgotinib, 39 placebo) were evaluated. At baseline, there were no notable differences between filgotinib and placebo for any MRI structural lesion types. From baseline to week 12, filgotinib was associated with a significant reduction in SI joint erosion score (p = 0.02) and increase in backfill score (p = 0.005) vs placebo, with no significant between-group differences for ankylosis (p = 0.46) or fat metaplasia (p = 0.17). At week 12, change in SPARCC MRI SI joint inflammation scores correlated positively with erosion scores but negatively with backfill scores.
Conclusion: The significant changes in MRI structural lesions induced by filgotinib in the SI joint by week 12 demonstrate that tissue repair can be observed very soon after starting treatment with a JAK1 preferential inhibitor. This could have prognostic implications for development of ankylosis.
Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03117270.
Keywords: Ankylosing spondylitis; filgotinib; inflammation; magnetic resonance imaging; sacroiliac joint; therapeutics.
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.