Impact of filgotinib on sacroiliac joint magnetic resonance imaging structural lesions at 12 weeks in patients with active ankylosing spondylitis (TORTUGA trial)

Walter P Maksymowych, Mikkel Østergaard, Robert Landewé, William Barchuk, Ke Liu, Chantal Tasset, Leen Gilles, Thijs Hendrikx, Robin Besuyen, Xenofon Baraliakos, Walter P Maksymowych, Mikkel Østergaard, Robert Landewé, William Barchuk, Ke Liu, Chantal Tasset, Leen Gilles, Thijs Hendrikx, Robin Besuyen, Xenofon Baraliakos

Abstract

Objective: To assess the effect of filgotinib, which preferentially inhibits Janus kinase 1 (JAK1), on MRI measures of structural change in the SI joint in patients with active AS in the TORTUGA trial.

Methods: Adults with active AS and inadequate response/intolerance to two or more NSAIDs 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 an 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, the 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, https://ichgcp.net/clinical-trials-registry/NCT03117270" title="See in 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.

Figures

Fig . 1
Fig. 1
Mean change from baseline to week 12 in the (A) total erosion score, (B) total backfill score, (C)total ankylosis score (D) and fat metaplasia.
Fig . 2
Fig. 2
Illustrative T1W MRI scans at (A) baseline and (B) week 12 from a patient who received filgotinib In (A) the arrows point to an extensive erosion of the left iliac bone on the T1W MRI scan. In (B) the arrows demonstrate the appearance of bright tissue filling in the cavity of the erosion, bordered by an irregular dark band. This is the characteristic appearance of backfill.
Fig . 3
Fig. 3
Cumulative probability of change from baseline to week 12 in (A) total erosion score, (B) total backfill score, (C) total ankylosis score and (D) fat metaplasia

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Source: PubMed

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