OP0141 EFFECTS OF FILGOTINIB ON SPINAL LESIONS IN ANKYLOSING SPONDYLITIS: MAGNETIC RESONANCE IMAGING DATA FROM THE TORTUGA TRIAL
Authors: X. Baraliakos, M. Østergaard, R. B. M. Landewé, W. Barchuk, K. Liu, C. Tasset, L. Gilles, T. Hendrikx, R. Besuyen, W. P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2021)

Background: The oral Janus kinase 1 preferential inhibitor filgotinib (FIL) significantly improved Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) inflammation scores (bone marrow oedema) in the spine and sacroiliac joints vs placebo (PBO) in the Phase 2 TORTUGA trial ( NCT03117270 ) in patients with active ankylosing spondylitis (AS). 1 Objectives: This post-hoc analysis evaluated the effects of FIL on Canada-Denmark (CANDEN) MRI measures of spinal inflammation and structural lesions in patients from the TORTUGA trial. Methods: TORTUGA was a PBO-controlled, multicentre, double-blind, randomised trial. Patients with active AS (as per modified New York classification criteria, with sacroiliitis confirmed by central reading) were treated with FIL 200 mg (n=58) or PBO (n=58) once daily for 12 weeks. MRI of the total spine was conducted at baseline and at treatment end. Scans were re-evaluated post-hoc by 2 independent experts (blinded to time point and assigned treatment) using the CANDEN method; 2 inter-reader discrepancies were resolved by an independent adjudicator. Observed changes from baseline were evaluated using analysis of covariance, with factors for treatment, baseline value, and randomisation stratification by prior tumour necrosis factor inhibitor use. Least-squares (LS) mean changes from baseline and between-group differences with 95% confidence intervals (CI) were calculated; P values are nominal. Results: MRI scans from 88 patients (47 FIL, 41 PBO) with an evaluable scan at baseline and Week 12 (or early termination) were re-evaluated. Baseline characteristics were generally similar between patients with/without an MRI scan. Of those with MRI scans, mean total spine inflammation score (which ranges from 0–614) was higher, and mean ankylosis score (which ranges from 0–460) was lower, in the FIL vs PBO group at baseline. Total spine inflammation scores decreased from baseline with FIL but not with PBO (Figure and Table; P=0.0003 for between-group difference). Cumulative probability plots favoured FIL over PBO for change from baseline in subregion inflammation scores, including posterolateral elements (i.e. sum of lesions in ribs, transverse processes, spinous processes, soft tissue inflammation, and postero-lateral vertebral body), facet joint, and vertebral body. Total spine fat lesion scores numerically increased from baseline in the FIL but not PBO group (P=0.0878 for between-group difference; Table). There were no significant differences between groups for changes in erosion (P=0.1956) or ankylosis (P=0.3888) scores (Table). Table 1. Change from baseline at Week 12 in CANDEN total spine inflammation, total spine fat, total spine bone erosion, and ankylosis scores Treatment group n Sample mean (SE ) LS mean (SE ) 95% CI of treatment mean LS mean of group difference (SE ) 95% CI of group difference Between-group P value Total spine inflammation score Filgotinib 47 –4.98 (0.96) –4.40 (1.13) –6.65, –2.15 –4.49 (1.21) –6.85, –2.12 0.0003 Placebo 41 0.29 (0.78) 0.09 (1.13) –2.17, 2.34 Total spine fat score Filgotinib 47 1.01 (0.62) 1.09 (0.66) –0.22, 2.40 1.18 (0.69) –0.18, 2.55 0.0878 Placebo 41 –0.25 (0.19) –0.09 (0.66) –1.40, 1.21 Total spine bone erosion score Filgotinib 47 0.01 (0.02) 0.07 (0.03) 0.00, 0.14 0.05 (0.04) –0.02, 0.12 0.1956 Placebo 41 –0.02 (0.03) 0.02 (0.03) –0.04, 0.09 Total ankylosis score Filgotinib 47 0.30 (0.29) 0.23 (0.31) –0.40, 0.85 0.28 (0.34) –0.37, 0.94 0.3888 Placebo 41 –0.01 (0.08) –0.06 (0.31) –0.68, 0.56 SE, standard error Conclusion: This is the first PBO-controlled trial to demonstrate a decrease in inflammatory activity with FIL, not only in the spinal vertebrae but also in the postero-lateral elements of the spine and facet joints. As expected in a 12-week study period, no changes in erosion or ankylosis were seen, while fat lesions showed a tendency to increase with FIL. Larger trials are needed to confirm these results. References: [1]van der Heijde D, et al. Lancet 2018;392:2378–87. [2]Krabbe S, et al. RMD Open 2019;5:e001057. Acknowledgements: The TORTUGA trial was sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Debbie Sherwood BSc, CMPP (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV. Disclosure of Interests: Xenofon Baraliakos Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Hexal, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB, Grant/research support from: AbbVie, Celgene, Novartis and UCB, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Roche, Sandoz, Sanofi and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Merck and Novartis, Robert B.M. Landewé Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering and UCB, Consultant of: AbbVie, Ablynx, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Roche, Schering, TiGenix and UCB, Grant/research support from: AbbVie, Amgen, Janssen (formerly Centocor), Novartis, Pfizer, Roche, Schering and UCB, Employee of: Director of Rheumatology Consultancy BV, William Barchuk Shareholder of: Gilead Sciences, Inc., Employee of: Currently employee of Gilead Sciences, Inc.; and former employee of AbbVie, Eli Lilly and Johnson &amp; Johnson, Ke Liu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Chantal Tasset Shareholder of: Galapagos, Employee of: Galapagos, Leen Gilles Employee of: Galapagos, Thijs Hendrikx Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited