Lb0001 efficacy and Safety of Filgotinib for Patients With Rheumatoid Arthritis With Inadequate Response to Methotrexate: Finch1 Primary Outcome Results

Abstract

BackgroundFilgotinib (FIL) is an orally administered, potent and selective inhibitor of Janus kinase 1 (JAK1) that has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA).ObjectivesTo evaluate efficacy and safety of FIL treatment in patients with RA who have had an inadequate response to methotrexate (MTX).MethodsThis phase 3, double-blind, active- and placebo (PBO)-controlled study randomized patients with active RA (3:3:2:3) to FIL 200 mg, FIL 100 mg, active comparator (adalimumab [ADA] 40mg every 2 weeks), or PBO daily for up to 52 weeks; results through week 24 are presented. Patients were also receiving MTX for ≥12 weeks with a stable dose of MTX for ≥4 weeks before initiation of study drug. Primary efficacy endpoint was proportion of patients achieving ACR20 response at week 12; additional clinical assessments were ACR50 and ACR70 responses, DAS28-CRP score ≤3.2 and <2.6, van der Heijde modified total Sharp score (mTSS), and patient-reported outcomes were HAQ-DI, SF-36 PCS, and FACIT-Fatigue. Safety endpoints included types and rates of adverse events. Logistic regression adjusting for stratification factors with nonresponder imputation was used for superiority test of FIL vs PBO for ACR response and other binary endpoints. Mixed-effect model adjusting for baseline value, stratification factors, treatment, visit, and treatment by visit interaction as fixed effects with observed cases was used for continuous endpoints. Non-inferiority test of FIL to ADA (preserving >50% of ADA response) was performed for DAS28-CRP ≤3.2 and <2.6.ResultsOf 1,759 patients randomized, 1,755 received study drug and were analyzed, with 475 FIL 200mg; 480 FIL 100mg; 325 ADA; and 475 PBO, of which 89.5%, 90.4%, 88.9%, and 81.3%, respectively, completed week 24 study drug. Most patients (81.8%) were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.6) years, and mean (SD) DAS28-CRP was 5.7 (0.9). At week 12, significantly more patients in the FIL 200mg and 100mg arms achieved an ACR20 response compared to PBO (Table 1). Similarly, compared to PBO, more patients receiving FIL achieved ACR50 and ACR70 responses, DAS28-CRP scores ≤3.2 and <2.6, had lower radiographic progression, and reported improvements in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Table 1). Non-inferiority of FIL 200mg to ADA was met based on DAS28-CRP ≤3.2. The FIL safety profile was consistent with prior studies through week 24 (Table 2).ConclusionsThe selective JAK1 inhibitor FIL, at doses of 200mg and 100mg led to significant improvement in signs and symptoms of RA, prevented radiographic progression, and improved physical function compared to PBO, and was well tolerated among patients with RA with prior inadequate response to MTX. Efficacy of FIL 200mg was non-inferior to ADA based on DAS28-CRP ≤3.2.Disclosure of InterestsBernard Combe Consultant for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Alan Kivitz Shareholder of: Novartis, Consultant for: Ab...

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

“…While two studies designed as non-inferiority trials have shown statistical superiority of baricitinib or upadacitinib compared with adalimumab (all in combination with MTX),80 81 a third study using tofacitinib+MTX did not show such superiority82; thus, the overall clinical relevance of small differences in clinical trials was not considered convincing enough for the task force to prefer tsDMARDs over bDMARDs. This conclusion is further supported by recently presented data revealing that filgotinib+MTX met non-inferiority for Disease Activity Score 28 <3.2, but not superiority criteria, when compared with adalimumab, a prespecified endpoint, although superiority was observed for some of the secondary endpoints 83. Importantly, in these studies various inflammatory markers, such as swollen joint counts, did not differ among the groups, in line with the hitherto unknown clinical relevance mentioned above.…”

Filgotinib, a JAK1 Inhibitor, Modulates Disease-Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials

“…The efficacy and safety of filgotinib as both an add-on to methotrexate (MTX) and a monotherapy have been demonstrated in two 24-week phase 2b studies in adult patients with moderately-toseverely active RA and an inadequate response to MTX (MTX-IR) [5,6]. These results were confirmed and extended in three phase 3 randomized clinical trials in MTX-IR, MTX-naïve, and biologic disease-modifying anti-rheumatic drug-IR moderately-to-severely active RA, which met 12-or 24-week primary endpoints for efficacy [8][9][10].…”

<p>JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data</p>

“…27 This meta-analysis included 4 RCTs; namely ORAL Strategy, RA-BEAM, FINCH1 & Fleischman 2019. 22,26,28,29 This meta-analysis showed that in RA patients with an inadequate response to MTX, baricitinib 4mg + MTX and upadacitinib 15mg + MTX showed the highest ACR response rates. Additionally, it demonstrated a significantly higher ACR20 response rate with both baricitinib 4mg + MTX and upadacitinib 15mg + MTX when compared to adalimumab 40mg + MTX.…”