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

Author:

Maksymowych Walter P1ORCID,Østergaard Mikkel23,Landewé Robert4,Barchuk William5,Liu Ke5,Tasset Chantal6,Gilles Leen7,Hendrikx Thijs8,Besuyen Robin9,Baraliakos Xenofon10ORCID

Affiliation:

1. Department of Medicine, University of Alberta, Edmonton, AB, Canada

2. Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup

3. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

4. Department of Rheumatology, Amsterdam University Medical Center, Amsterdam and Zuyderland Medical Center, Heerlen, The Netherlands

5. Clinical Research, Gilead Sciences, Foster City, CA, USA

6. Late Stage Development, Galapagos NV

7. Biostatistics, LACO, Contracted by Galapagos NV, Mechelen, Belgium

8. Medical Affairs

9. Clinical Development, Galapagos BV, Leiden, The Netherlands

10. Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany

Abstract

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, http://clinicaltrials.gov, NCT03117270

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

Reference30 articles.

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2. Therapies in ankylosing spondylitis—from clinical trials to clinical practice;Tahir;Rheumatology (Oxford),2018

3. New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice;Dubash;Ther Adv Chronic Dis,2018

4. One year in review 2018: axial spondyloarthritis;Carli;Clin Exp Rheumatol,2019

5. The pathogenesis of ankylosing spondylitis: an update;Pedersen;Curr Rheumatol Rep,2019

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