LAUSR

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).To compare the efficacy of FILG 200 mg + MTX with TOFA 5 mg + MTX using matching adjusted indirect comparison (MAIC).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)<2.6, Boolean) between FILG + MTX vs TOFA 5 mg + MTX relative to ADA 40 mg + MTX.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 < .05) and 8.3% (p < .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 < .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 < .05) [Figure 2] as well as numerical improvements on other efficacy outcomes.Table 1.Baseline Characteristics of FINCH-1 vs ORAL STRATEGYCHARACTERISTICBEFORE MATCHINGAFTER MATCHINGORAL STRATEGYFILG 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 deviationFigure 1.ACR20/50/70 relative to ADA 40 mg+ MTX of FILG 200 mg + MTX vs TOFA 5 mg + MTX * p < .05Figure 2.Clinical Remission outcomes relative to ADA 40 mg+ MTX of FILG 200 mg + MTX vs TOFA 5 mg + MTX * p < .05In 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.[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): 457-468The study was funded by Gilead Sciences IncMahdi 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