Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. ORAL Solo¹ and ORAL Sync² are two Phase 3 index studies that demonstrated the efficacy of tofacitinib in adult patients (pts) with RA who were DMARD inadequate responders (DMARD-IR). Early onset of effect is a clinically meaningful endpoint. This post-hoc analysis examined the magnitude and durability of early response to tofacitinib in ORAL Solo and ORAL Sync.

Methods: ORAL Solo and ORAL Sync were double-blind, placebo (PBO)-controlled, parallel-group studies in pts with active RA and an inadequate response to ≥1 conventional synthetic (cs) or biologic (b) DMARD.^1,2 Pts were randomized to tofacitinib 5 mg BID, tofacitinib 10 mg BID, PBO advanced to tofacitinib 5 mg BID, or PBO advanced to tofacitinib 10 mg BID, either as monotherapy in ORAL Solo or with background csDMARD in ORAL Sync. In ORAL Solo, pts randomized to PBO were advanced to tofacitinib at Month 3; in ORAL Sync, pts randomized to PBO were advanced to tofacitinib at Month 3 (non-responders) or Month 6 (all other pts). In this post-hoc analysis, the following clinical efficacy data for pts on tofacitinib or PBO (prior to advancement to tofacitinib) ± csDMARD, were evaluated at Week 2, Month 3, and Month 6 (ORAL Sync only; no Month 6 PBO comparison in ORAL Solo): change from baseline in Clinical Disease Activity Index (CDAI) >12,³ HAQ-DI change from baseline ≥0.22, CDAI ≥50% improvement from baseline, CDAI ≥70% improvement from baseline, CDAI ≥85% improvement from baseline, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score improvement from baseline ≥4, Pain visual analog scale (VAS) score change from baseline ≥10. This analysis is post hoc and multiplicity adjustment was done.

Results: Clinical efficacy endpoint data are summarized in Table 1. At Week 2, more patients receiving tofacitinib 5 or 10 mg BID ± csDMARDs (compared to PBO ± csDMARDs) achieved a CDAI change from baseline >12, HAQ-DI improvement from baseline ≥0.22, CDAI ≥50% improvement from baseline and pain VAS change from baseline ≥10. By Month 3, more pts receiving tofacitinib 5 or 10 mg BID ± csDMARDs (compared to PBO ± csDMARDs) achieved the efficacy outcomes measured including improvements from baseline in FACIT-F scores ≥4, CDAI ≥50%, CDAI ≥70%, and CDAI ≥85% improvement from baseline. Responses attained at Month 3 were maintained or increased at Month 6.

Conclusion: DMARD-IR pts with active RA receiving tofacitinib ± csDMARDs appeared to show greater improvements compared to PBO in clinical disease activity, HAQ-DI, and pain as early as Week 2 (first post-baseline assessment), and improvements in fatigue by Month 3. Responses were maintained or improved through Month 3 (monotherapy) or Month 6 (with background DMARD). References: 1. Fleischmann R et al.  N Engl J Med 2012; 367: 495-507. 2. Kremer J et al.  Ann Intern Med 2013; 159: 253-261. 3. Curtis JR et al.  Arthritis Care Res (Hoboken ) 2015; 67: 1345-1353.