SAT0142 MATCHING ADJUSTED INDIRECT COMPARISON OF FILGOTINIB VS. TOFACITINIB IN MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE TO METHOTREXATE
Authors: M. Gharaibeh, N. Smith, S. Jeyakumar, E. Mark, S. Shreay
Journal: Annals of the Rheumatic Diseases (2020)

Background: Filgotinib (FILG) is a JAK1 inhibitor that has been investigated in combination with methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA). To date, no head-to-head trial has compared the efficacy of FILG versus tofacitinib (TOFA). Objectives: To compare the efficacy of FILG 200 mg + MTX with TOFA 5 mg + MTX using matching adjusted indirect comparison (MAIC). Methods: MAIC technique uses individual patient data (IPD) from one trial and aggregate data from the other to enable comparison of outcomes after matching on baseline characteristics [1]. An anchored MAIC was conducted using IPD from the FINCH-1 trial of FILG 200 mg + MTX vs adalimumab (ADA) 40 mg + MTX and published data from ORAL STRATEGY [2] trial of TOFA 5 mg + MTX vs ADA 40 mg + MTX. Patients in the FINCH-1 trial were reweighted based on age, sex, race, tender joint count 28, swollen joint count 28, C-reactive protein and patient’s global assessment to match baseline characteristics of the comparator. After matching, Wald tests were used to test for significant differences in ACR 20/50/70 and clinical remission outcomes (SDAI≤3.3, CDAI≤2.8, DAS28(CRP)&lt;2.6, Boolean) between FILG + MTX vs TOFA 5 mg + MTX relative to ADA 40 mg + MTX. Results: After matching, baseline characteristics were balanced across the trial populations [Table 1]. FILG 200 mg + MTX patients experienced significantly greater improvement in 12 week ACR50 and ACR70 outcomes compared to TOFA 5 mg + MTX with a mean difference in difference (DD) of 13.5% (p &lt; .05) and 8.3% (p &lt; .05) respectively, as well as numerical improvements on other ACR outcomes at 12, 24 and 52 weeks [Figure 1]. At 24 weeks, FILG 200 mg + MTX patients experienced significantly greater improvement in DAS28(CRP) clinical remission compared to TOFA 5 mg + MTX with DD of 10.1% (p &lt; .05) [Figure 2] as well as numerical improvements on other efficacy outcomes. At 52 weeks, FILG 200 mg + MTX patients experienced significantly greater improvement in DAS28(CRP) clinical remission compared to TOFA 5 mg + MTX with DD of 13.2% (p &lt; .05) [Figure 2] as well as numerical improvements on other efficacy outcomes. Table 1. Baseline Characteristics of FINCH-1 vs ORAL STRATEGY CHARACTERISTIC BEFORE MATCHING AFTER MATCHING ORAL STRATEGY FILG 200 + MTX (N=475 ) ADA + MTX (N=325 ) FILG 200 + MTX (ESS=340 ) ADA + MTX (ESS=233 ) TOFA 5mg + MTX BID (N=376 ) ADA + MTX BID (N=386 ) Sex – Female, % 79.8% 81.8% 83.0% 83.0% 83.0% 83.0% Age (year), mean (SD ) 51.8 (12.8) 53.3 (12.9) 50.0 (13.4) 50.7 (13.4) 50.0 (13.4) 50.7 (13.4) Race – White, % 65.7% 70.5% 76.0% 76.0% 76.0% 76.0% Tender Joint Count 28, mean (SD ) 15.0 (6.4) 14.6 (6.3) 15.6 (6.5) 15.2 (6.7) 15.6 (6.5) 15.2 (6.7) Swollen Joint Count 28, mean (SD ) 11.2 (5.2) 11.2 (5.0) 11.8 (5.7) 11.0 (5.4) 11.8 (5.7) 11.0 (5.4) C-Reactive Protein (mg/L), mean (SD ) 16.1 (21.0) 14.6 (18.0) 18.7 (21.9) 16.7 (21.3) 18.7 (21.9) 16.7 (21.3) Patient global assessment baseline, mean (SD ) 67.1 (19.2) 67.0 (19.1) 61.7 (22.0) 60.2 (23.5) 61.7 (22.0) 60.2 (23.5) ESS = effective sample size; SD = standard deviation Figure 1. ACR20/50/70 relative to ADA 40 mg+ MTX of FILG 200 mg + MTX vs TOFA 5 mg + MTX * p &lt; .05 Figure 2. Clinical Remission outcomes relative to ADA 40 mg+ MTX of FILG 200 mg + MTX vs TOFA 5 mg + MTX * p &lt; .05 Conclusion: In this MAIC, compared to TOFA 5 mg + MTX, FILG 200 mg + MTX appears to produce improved efficacy outcomes (ACR20/50/70, DAS28(CRP), SDAI, CDAI and Boolean Remission) at weeks 12, 24 and 52. References: [1]Signorovitch JE, et al. “Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.” Value in Health 15.6 (2012): 940-947 [2]Fleischmann R, et al. “Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy).” The Lancet 390.10093 (2017): 457-468 Acknowledgments: The study was funded by Gilead Sciences Inc Disclosure of Interests: Mahdi Gharaibeh Shareholder of: Gilead Sciences Inc, Employee of: Gilead Sciences, Amgen, Nate Smith Consultant of: Gilead Sciences Inc, Sushanth Jeyakumar Consultant of: Gilead Sciences, Ejim Mark Shareholder of: Gilead Sciences Inc, Employee of: Gilead Sciences, Novartis, Sanatan Shreay Shareholder of: Gilead Sciences, Employee of: Gilead Sciences