Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post-hoc analysis of data from Phase 3 studies investigated the efficacy of tofacitinib in patients (pts) according to RA duration (early vs late).

Methods: Pts from 5 placebo-controlled Phase 3 studies (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307], ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]) of tofacitinib as monotherapy or with background DMARDs were included. This analysis included pts who were inadequate responders (IR) to ≥1 DMARDs randomized to tofacitinib 5 mg or 10 mg BID, placebo or adalimumab (ORAL Standard); results for tofacitinib 5 mg BID are presented. Pts were evaluated according to RA duration at baseline (years [yr]): ≤1 vs >1; ≤2 vs >2; ≤3 vs >3. For each subset pair, at Month 3 and Month 6 we evaluated proportions of pts achieving ACR20/50/70 response, Disease Activity Score (ESR) (DAS 28-4[ESR]) <2.6 (remission), DAS28-4(ESR) ≤3.2 (low disease activity), HAQ-DI minimal clinically important difference (MCID) ≥0.22, 0.30, 0.50, and 0.80, and mean changes from baseline in DAS28-4(ESR) and HAQ-DI scores. Odds ratios (ORs [for rates]) and mean differences (for change from baseline) were calculated with corresponding 95% CIs, and 2-sided p values (‘>’ category as reference). Non-responder imputation (NRI) was applied for rates. Pts meeting criteria for rescue (failed to achieve ≥20% improvement from baseline at Month 3 in applicable studies) had NRI applied or were excluded from mean change analyses at Month 6.

Results: At Month 3, significantly greater OR for ACR20, ACR50, HAQ-DI MCID ≥0.22, and ≥0.30 were shown for ≤1 vs >1 yr and ≤2 vs >2 yr subsets (Figure). HAQ-DI MCID ≥0.50 and ≥0.80 were significantly greater for ≤1 vs >1 yr, ≤2 vs >2 yr, and ≤3 vs >3 yr subsets. For all other efficacy outcomes, ORs were not statistically significant between subsets at Month 3. Mean changes from baseline in DAS28-4(ESR) were significantly greater for ≤1 vs >1 yr and ≤2 vs >2 yr subsets at Month 3 (Table). Mean changes from baseline in HAQ-DI at Month 3 was significantly greater for ≤1 vs >1 yr, ≤2 vs >2 yr, and ≤3 vs >3 yr subsets. In general, higher responses were seen at Month 3 in pts with early vs late RA disease duration.

Conclusion: In this analysis, a trend was observed indicating that DMARD-IR pts with earlier disease duration at treatment initiation respond better to tofacitinib 5 mg BID than pts with late disease duration. Results suggest that initiating tofacitinib earlier in the disease may yield greater treatment response and thereby reduce the time pts experience active disease.