POS0905 EARLY MEANINGFUL IMPROVEMENTS IN SPINAL PAIN AND CORRELATION WITH OTHER CLINICAL OUTCOMES IN PATIENTS TREATED WITH FILGOTINIB FOR RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: A POST HOC ANALYSIS OF THE PHASE 2 TORTUGA TRIAL

Background: Pain is the most common symptom for patients with radiographic axial spondyloarthritis (r-axSpA; also known as ankylosing spondylitis) and is considered the most relevant by patients.[1,2] Pain may be present for several years before structural damage is detected.[1] Filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, significantly reduced disease activity in patients with active r-axSpA in the placebo-controlled Phase 2 TORTUGA trial.[3] Objectives: To assess the effect of filgotinib on spinal pain in patients with r-axSpA, and to evaluate the correlation between changes in spinal pain and other clinical outcomes. Methods: TORTUGA (NCT03117270) was a randomized, double-blind, placebo-controlled Phase 2 study of adult patients with active r-axSpA in Europe. Patients with an inadequate response or intolerance to ≥2 nonsteroidal anti-inflammatory drugs received filgotinib 200 mg or placebo once daily for 12 weeks. In this post hoc analysis, change from baseline in the following endpoints was assessed at Week 1, 2, 4, 8 and 12 (using last observation carried forward for missing data): patient's assessment of spinal pain (PASP) total score (average of overall and nocturnal spinal pain due to r-axSpA; range 0–10); PASP nocturnal pain score; and overall level of spinal pain based on the answer to question 2 of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. At each timepoint, the proportion of patients achieving a decrease from baseline of ≥1 in PASP total score, and the proportion achieving a ≥30% and ≥50% improvement from baseline in PASP total score, was determined using nonresponder imputation. The correlation between change from baseline in PASP total score and change from baseline in the following endpoints was measured using the Pearson correlation coefficient in patients treated with filgotinib with data for both endpoints: Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue; BASDAI question 1 (fatigue); Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire; patient's global assessment of disease activity (PGADA); 36-Item Short Form Health Survey (SF-36) Physical and Mental Component Summary (PCS and MCS) scores; Bath Ankylosing Spondylitis Functional Index (BASFI); C-reactive protein (CRP) level; and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scoring of inflammation in the sacroiliac joint and spine. Results: 116 patients were enrolled and received filgotinib 200 mg (n=58) or placebo (n=58). Mean (SD) time since diagnosis of axSpA was 6 (5.5) years in the filgotinib group and 8 (7.6) years in the placebo group. Mean (SD) PASP total score at baseline was 7.5 (1.2) and 7.4 (1.3) in the filgotinib and placebo groups, respectively. At Week 2, the least squares (LS) mean (95% CI) change from baseline in PASP total score was −1.6 (−2.2, −1.1) in the filgotinib group vs −1.1 (−1.7, −0.6) in the placebo group, increasing to −2.7 (−3.4, −1.9) vs −1.6 (−2.3, −0.9) at Week 12 (Figure 1A). Mean (SD) PASP nocturnal pain score at baseline was 7.4 (1.5) and 7.2 (1.6) in the filgotinib and placebo groups, respectively. At Week 2, the LS mean (95% CI) change from baseline in PASP nocturnal pain score was −1.7 (−2.3, −1.1) in the filgotinib group vs −1.1 (−1.7, −0.5) in the placebo group, increasing to −2.6 (−3.4, −1.8) vs −1.5 (−2.2, −0.7) at Week 12 (Figure 1B). At Week 2, the LS mean (95% CI) change from baseline in the overall level of spinal pain, based on the answer to BASDAI question 2, was −1.5 (−2.1, −0.9) with filgotinib vs −1.0 (−1.6, −0.4) with placebo, increasing to −2.6 (−3.5, −1.8) vs −1.6 (−2.4, −0.8) at Week 12. The proportion of patients (95% CI) achieving a decrease of ≥1 in PASP total score was 67.2% (54.4, 77.9) in the filgotinib group vs 56.9% (44.1, 68.8) in the placebo group at Week 2, and 87.9% (77.1, 94.0) vs 69.0% (56.2, 79.4) at Week 12. The proportion of patients (95% CI) achieving ≥30% improvement from baseline in PASP total score was 36.2% (25.1, 49.1) with filgotinib vs 20.7% (12.3, 32.8) with placebo at Week 2, increasing to 63.8% (50.9, 75.0) vs 36.2% (25.1, 49.1) at Week 12 (Figure 1C). The proportion of patients (95% CI) achieving a ≥50% improvement in PASP total score was 10.3% (4.8, 20.8) in the filgotinib group vs 3.4% (1.0, 11.7) in the placebo group at Week 2, increasing to 34.5% (23.6, 47.3) vs 19.0% (10.9, 30.9) at Week 12. Pearson correlation coefficients for the correlation between change from baseline in PASP total score and other study endpoints at Week 2 and 12 are shown in Table 1. Change from baseline in PASP total score at Week 12 correlated moderately to strongly with BASFI (0.75), BASDAI question 1 (fatigue; 0.68), PGADA (0.86) and SF-36 PCS (−0.63); all p<0.01. Change from baseline in PASP total score at Week 12 showed only a weak or no correlation with CRP level, SF-36 MCS and SPARCC MRI scoring of the sacroiliac joint and spine. Conclusion: Results of this post hoc analysis of TORTUGA show patients with r-axSpA treated with filgotinib had rapid reductions in spinal pain, with improvements vs placebo observed after 2 weeks. Improvements in spinal pain were associated with improvements in fatigue, physical function and quality of life. Given the lack of correlation between change in spinal pain and change in CRP level or inflammation on MRI, further studies are needed to understand the effect of JAK inhibition on pain nociceptive and non-nociceptive mechanisms in axSpA. REFERENCES: [1] Navarro-Compán V, et al. Ann Rheum Dis 2021;80:1511–21. [2] Selmi C, et al. Front Immunol 2024;15:1341981. [3] van der Heijde D, et al. Lancet 2018;392:2378–87. Figure 1 . Acknowledgements: We thank the physicians and patients who participated in this study. The TORTUGA trial was funded by Galapagos NV. This analysis was funded by Alfasigma S.p.A. (Bologna, Italy). Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Alfasigma S.p.A. Publication coordination was provided by Steve Winter, PhD, and funded by Alfasigma S.p.A. The authors acknowledge the contributions of Mohsine El Ghazi and Francesco De Leonardis to the study. Disclosure of Interests: Xenofon Baraliakos Paid instructor: AbbVie, Alfasigma S.p.A., Amgen, BMS, Celltrion, Cesas, Galapagos, Janssen, Lilly, Moonlake, Novartis, Pfizer, Roche, Sandoz, Springer, Stada, Takeda, UCB and Zuellig, Speaker's bureau: AbbVie, Alfasigma S.p.A., Amgen, BMS, Celltrion, Cesas, Galapagos, Janssen, Lilly, Moonlake, Novartis, Pfizer, Roche, Sandoz, Springer, Stada, Takeda, UCB and Zuellig, Consultant: AbbVie, Alfasigma S.p.A., Amgen, BMS, Celltrion, Cesas, Galapagos, Janssen, Lilly, Moonlake, Novartis, Pfizer, Roche, Sandoz, Springer, Stada, Takeda, UCB and Zuellig, Grant/research support: AbbVie, Celltrion, Moonlake and Novartis, Francesco Ciccia Speaker's bureau: AbbVie, Alfasigma S.p.A., AstraZeneca, GSK, Johnson&Johnson, Lilly, Novartis and Pfizer, Grant/research support: Novartis and Pfizer, Karl Gaffney Speaker's bureau: AbbVie, Lilly, Novartis and UCB, Shareholder: Rheumatology Events (www.rheumatologyevents.org), Consultant: AbbVie, Lilly, Novartis, Pfizer and UCB, Grant/research support: AbbVie, Alfasigma S.p.A., Biogen, Celltrion, Janssen, Lilly, Medac Pharma, NASS, Novartis, Pfizer, UCB and Versus Arthritis, Lien Gheyle Employee: Alfasigma S.p.A., Leen Gilles Shareholder: Johnson&Johnson, Employee: Alfasigma S.p.A., Victoria Navarro-Compán Speaker's bureau: AbbVie, Alfasigma S.p.A., Fresenius Kabi, Lilly, Novartis, Pfizer and UCB, Consultant: AbbVie, Alfasigma S.p.A., Lilly, Novartis, Pfizer and UCB, Grant/research support: AbbVie and Novartis, Margarita Romero Duran Employee: Alfasigma S.p.A., Filip van den Bosch Consultant: AbbVie, Alfasigma S.p.A., Fresenius Kabi, Grey Wolf Therapeutics, Janssen, Lilly, Novartis and UCB. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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