Ab0290 effect of filgotinib on pain in patients with rheumatoid arthritis in the phase 3 finch 1, 2 and 3 studies

Background Patients (pts) with rheumatoid arthritis (RA) often experience substantial pain despite treatment, and pain control is considered an important treatment outcome. The FINCH 1–3 studies demonstrated the efficacy and acceptable safety of the preferential Janus kinase (JAK) 1 inhibitor filgotinib (FIL) in pts living with RA. Objectives This post-hoc analysis of the FINCH studies assessed specific effects of FIL on pain. Methods FINCH 1–3 ( NCT02889796 , NCT02873936 , NCT02886728 ) were Phase 3, randomized, double-blind trials of FIL 100 mg and 200 mg (FIL100/200). In FINCH 1, pts with an inadequate response (IR) to methotrexate (MTX) received FIL, adalimumab (ADA) or placebo (PBO) + MTX for 52 weeks. In FINCH 2, pts with an IR to biologic disease-modifying anti-rheumatic drugs (DMARDs) received FIL or PBO + conventional synthetic DMARDs for 24 weeks. In FINCH 3, MTX-naïve pts received FIL ± MTX or MTX for 52 weeks. For each treatment group, pts reported pain on a 100-mm visual analog scale (VAS). Scores of ≤10 mm reflected limited to no pain; scores of ≤20 mm indicated health status was not negatively affected by pain. [1] Time to first VAS score of ≤10 mm was assessed. The proportion of pts who achieved remission (as per Disease Activity Score 28 with C-reactive protein [DAS28-CRP] <2.6 or Clinical Disease Activity Index [CDAI] ≤2.8) at Week 24 was evaluated. Of pts who achieved DAS28-CRP or CDAI remission, the proportion who also reported VAS pain scores of ≤10 mm or ≤20 mm was determined. Results In FINCH 1, there was a higher probability of achieving a VAS pain score of ≤10 mm with FIL200, vs ADA + MTX or PBO + MTX; responses were better or comparable with FIL100 vs other treatment arms ( Figure 1 ). Similar findings were observed in FINCH 2 and 3 for FIL vs PBO and MTX, respectively. In FINCH 1, the proportion of pts achieving DAS28-CRP remission was greater with FIL200 + MTX (48.4%) and comparable for the FIL100 + MTX (35.2%) vs ADA + MTX arms (35.7%; Table 1 ). Further, the proportion of pts who achieved VAS pain scores of ≤10 mm and ≤20 mm in addition to DAS28-CRP remission was 26.3% and 35.8%, respectively, in the FIL200 + MTX group, compared with 17.2% and 24.6% in the ADA + MTX group ( Table 1 ). In FINCH 2 and 3, a greater proportion of pts in the FIL groups achieved remission vs the PBO or MTX arms, respectively. A greater proportion of pts achieved pain responses in addition to DAS28-CRP remission in the FIL groups of FINCH 2 and FINCH 3 compared with PBO or MTX, respectively. Findings were similar when CDAI remission was assessed. Conclusion FIL positively affected pain parameters across the FINCH studies as early as Week 2, with responses sustained over time (up to Week 52 [FINCH 1 and 3] and Week 24 [FINCH 2]). In FINCH 1, FIL200 had a particularly favorable impact when pain response and remission were assessed together. Similar findings were seen with FIL compared with PBO and MTX in FINCH 2 and 3, respectively. These findings suggest that JAK inhibition may offer potential added value with respect to patient-reported pain outcomes when treat-to-target goals are met. Reference [1] Taylor PC, et al. J Clin Med 2019;8:831 Table 1. Disease response and improvement in VAS pain score (up to Week 24) FINCH 1 FIL200 + MTX (n=475) FIL100 + MTX (n=480) ADA + MTX (n=325) PBO + MTX (n=475) DAS28-CRP remission 230 (48.4) 169 (35.2) 116 (35.7) 77 (16.2) With VAS ≤10 mm 125 (26.3) 86 (17.9) 56 (17.2) 36 (7.6) With VAS ≤20 mm 170 (35.8) 120 (25.0) 80 (24.6) 55 (11.6) FINCH 2 FIL200 + MTX (n=147 ) FIL100 + MTX (n=153 ) PBO (n=148 ) DAS28-CRP remission 45 (30.6) 40 (26.1) 18 (12.2) With VAS ≤10 mm 23 (15.6) 19 (12.4) 8 (5.4) With VAS ≤20 mm 32 (21.8) 27 (17.6) 10 (6.8) FINCH 3 FIL200 + MTX (n=416 ) FIL100 + MTX (n=207 ) FIL200 (n=210 ) MTX (n=416 ) DAS28-CRP remission 225 (54.1) 88 (42.5) 89 (42.4) 121 (29.1) With VAS ≤10 mm 138 (33.2) 57 (27.5) 49 (23.3) 62 (14.9) With VAS ≤20 mm 169 (40.6) 64 (30.9) 68 (32.4) 79 (19.0) ADA, adalimumab; DAS28-CRP, Disease Activity Score-28 with C-reactive protein; FIL(100/200), filgotinib (100/200 mg); MTX, methotrexate; PBO, placebo; VAS, visual analog scale. Acknowledgements The authors thank the physicians and patients who participated in the studies. The studies were funded by Gilead Sciences (Foster City, CA, USA) and Galapagos NV (Mechelen, Belgium). Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and was funded by Galapagos NV. Disclosure of Interests Peter C. Taylor Speakers bureau: AbbVie, Consultant of: AbbVie, Biogen, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Sanofi, UCB Pharma, Grant/research support from: Galapagos, Arthur Kavanaugh Consultant of: AbbVie, Amgen, BMS, Janssen, Novartis, Pfizer, UCB, Peter Nash Speakers bureau: AbbVie, Amgen, BMS, Celgene, Gilead/Galapagos, Janssen, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, BMS, Celgene, Gilead/Galapagos, Janssen, Lilly, Novartis, Pfizer, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Gilead/Galapagos, Janssen, Lilly, Novartis, Pfizer, Janet Pope: None declared, Georg Pongratz Speakers bureau: AbbVie, Boehringer, Lilly, Pfizer, Roche, Sanofi, Paid instructor for: Lilly, Roche, Consultant of: AbbVie, Boehringer, Galapagos, Lilly, Pfizer, Roche, Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, Sobi, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Rieke Alten Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB, Viatris, Ken Hasegawa Shareholder of: Gilead, Employee of: Gilead, Shangbang Rao Employee of: Gilead, Dick de Vries Shareholder of: Galapagos, Employee of: Galapagos, Pieter-Jan Stiers Employee of: Galapagos, Chris Watson Shareholder of: Galapagos, Employee of: Galapagos, Rene Westhovens Speakers bureau: Celltrion, Galapagos, Gilead, Consultant of: Celltrion, Galapagos, Gilead.