Background/Purpose: In the Phase 2 TORTUGA trial (NCT03117270), the oral, selective Janus kinase 1 inhibitor filgotinib reduced inflammation in patients with active ankylosing spondylitis (AS), as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores (van der Heijde D, et al. Lancet 2018;392:2378–87). In this post hoc analysis, we compared the effects of filgotinib on MRI measures of structural change in the sacroiliac joint (SIJ) with effects on clinical parameters.

Methods: TORTUGA was a randomized trial of 116 patients with active AS (as per modified New York classification criteria, with sacroiliitis confirmed by central reading) treated with filgotinib 200 mg (n=58) or placebo (n=58) once daily for 12 weeks. MRI scans at baseline and Week 12 (or early discontinuation) were re‑evaluated post hoc in a blinded fashion by 2 experts to determine SPARCC SIJ Structural Scores (SSS); erosion, backfill, ankylosis, and fat lesion scores. Observed changes from baseline in the SPARCC SSS measures were evaluated using analysis of covariance with factors for treatment, baseline value, and randomization stratification. Least squares mean changes from baseline and between-group differences with 95% confidence intervals were calculated; p values were nominal. Data were then compared with clinical outcomes. Pearson correlations to assess intra-subject relationships were determined for changes in structural lesions from baseline to Week 12 versus changes in C-reactive protein, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and SPARCC MRI SIJ and spine inflammation scores.

Results: Evaluable MRI scans (baseline and Week 12) were obtained from 87 patients (48 filgotinib, 39 placebo). At baseline, there were no notable differences in MRI structural lesions (erosion, backfill, ankylosis, or fat lesion scores) between filgotinib and placebo (Table 1). From baseline to Week 12, erosion scores decreased with filgotinib and increased with placebo (p=0.02 for between-group difference; Table 1). Backfill scores increased with filgotinib but not placebo (p=0.005). There were no significant between‑group differences in the change from baseline to Week 12 for ankylosis (p=0.46) or fat lesions (p=0.17) (Table 1). At Week 12, changes in erosion scores were positively correlated with changes in SPARCC MRI SIJ inflammation scores (filgotinib: r=0.35921, p=0.0132; placebo: r=0.56043, p=0.0002; Table 2), indicating that changes in inflammation and structural scores occur together in the same individual. A negative correlation was observed for backfill (filgotinib: r=–0.41479, p=0.0037; placebo: r=–0.37483, p=0.0187; Table 2). All observed correlations were moderate. Overall, significant correlations with erosion and backfill scores were not observed for other clinical endpoints, or for any clinical endpoint with ankylosis or fat lesion scores (Table 2).

Conclusion: In the 12-week TORTUGA trial, filgotinib was associated with a decrease in SIJ inflammation compared with placebo—as assessed by MRI—that correlated with a decrease in SIJ erosions and an increase in backfill.

Table 1. SPARCC SIJ SSS. CI, confidence interval; LSM, least squares mean; SD, standard deviation; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada; SSS, SIJ structural scores

Table 2. Pearson correlations between change from baseline to Week 12 in clinical and MRI inflammation endpoints and MRI structural lesions. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; CRP, C-reactive protein; MRI, magnetic resonance imaging; R, Pearson correlation; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-filgotinib-on-structural-lesions-in-the-sacroiliac-joints-at-12-weeks-in-patients-with-active-ankylosing-spondylitis-correlation-with-clinical-endpoints/