Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Patients (pts) with RA generally receive conventional synthetic DMARDS (csDMARDs) as first-line therapy, and inadequate responders (IR) to csDMARDs generally receive biological DMARDs (bDMARDs). We evaluated the efficacy and safety of tofacitinib in 3 RA pt populations (popns) who had incomplete response or were intolerant to prior lines of therapy (both referred to as IR).

Methods: Data from pts who were 1) non-MTX csDMARD-IR but not bDMARD-IR; 2) MTX-IR but not bDMARD-IR; and 3) bDMARD-IR (referred to as non-MTX csDMARD-IR, MTX-IR, and bDMARD-IR) were pooled from 8 Phase 2 and 6 Phase 3 trials evaluating the efficacy and safety of tofacitinib 5 or 10 mg BID vs placebo (PBO) in RA. Pts may have received >1 prior csDMARD, and in ~60% of the studies tofacitinib was given in combination with a csDMARD, commonly MTX. Month (M)3 efficacy outcomes included % of pts achieving ACR20/50/70 responses or Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR])<2.6 (remission), and change from baseline (BL) in DAS28-4(ESR) or HAQ-DI scores. No multiplicity adjustments were made. Crude incidence rates (CIR; unique pts with events/100 pt-yrs) based on adverse events (AEs) through M24 were calculated as safety outcomes.

Results: The non-MTX csDMARD-IR, MTX-IR, and bDMARD-IR popns comprised a total of 537, 3113, and 782 pts, respectively (Table; the non-MTX csDMARD-IR and bDMARD-IR popns were substantially smaller). Prior csDMARDs received by the total non-MTX csDMARD-IR, MTX-IR, and bDMARD-IR popns were chloroquine (17.7%, 13.8%, 4.1%), hydroxychloroquine (37.2%, 21.2%, 19.8%), leflunomide (19.4%, 20.5%, 24.2%), MTX (7.3% [not IR to MTX], 100%, 95.5%), sulfasalazine (31.1%, 26.8%, 18.0%), and others (8.0%, 10.7%, 10.4%), respectively. BL characteristics were similar between non-MTX csDMARD-IR, MTX-IR, and bDMARD-IR popns except for mean RA duration (5.2–7.2, 8.1–8.6, and 11.6–12.2 yrs, respectively). Most pts were female (80.3–85.4%), mean age range was 49.7–54.6 yrs, and mean DAS28-4(ESR) score ranged from 6.2–6.5. Significantly higher ACR response rates and greater changes from BL in DAS28-4(ESR) and HAQ-DI scores at M3 were recorded with tofacitinib 5 and 10 mg BID in all popns vs PBO (Table). A trend was observed for numerically higher proportions of non-MTX csDMARD-IR pts achieving efficacy outcomes vs MTX-IR and bDMARD-IR popns. CIRs for TEAEs, SAEs, and DC due to AEs were numerically lower in the non-MTX csDMARD-IR popn vs the MTX-IR popn and both popns had lower CIRs vs the bDMARD-IR popn. For numerical differences, 95%CIs generally overlap. AEs of special interest are reported (Table).

Conclusion: Tofacitinib is associated with improved efficacy and most safety outcomes vs PBO in each of the non-MTX csDMARD-IR, MTX-IR, and bDMARD-IR popns, and may be more efficacious when used in earlier lines of therapy.