THU0153 Improvements in disease activity score by baseline status: Pooled analysis of five phase 3 studies with tofacitinib (CP-690,550) in patients with active rheumatoid arthritis

Background Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator in rheumatoid arthritis. Objectives To assess efficacy of tofacitinib 5 and 10 mg twice-daily (BID) using disease activity scores (DAS) across a wide range of baseline (BL) values. Methods Demographic and BL disease characteristics of patients (pts) in five Phase 3 studies (monotherapy: NCT00814307; background DMARD: NCT00960440, NCT00847613, NCT00856544, NCT00853385) were similar. Data were pooled, and BL DAS values based on 28-joint counts using C-reactive protein (DAS28-3(CRP)) were divided into four groups (≤25th, >25th-50th, >50th-75th, >75th percentiles); for each, mean change from BL, proportion of pts improving by ≥1.2 from BL, and proportions of pts with values ≤3.2 and 4.71-5.34 (Q2); >5.34-6.01 (Q3); >6.01 (Q4). In each group, both tofacitinib doses demonstrated clinically significant improvements in DAS28-3(CRP)-based analyses compared with PBO. Pts with higher BL values had greater mean reductions in DAS, with correspondingly larger differences from PBO. All BL groups showed numerical benefit of 10 mg BID over 5 mg BID across all DAS28-3(CRP)-based analyses and the proportions of pts achieving various DAS thresholds were 2-13 percentage points greater with 10 mg BID vs 5 mg BID. Data for Q1 and Q4 are shown in Table 1. Table 1. DAS28-3(CRP)-based analyses for Q1 and Q4 at Month 3 BL QuartileTreatmentDAS28-3(CRP) Mean Δ from BLImprovement ≥1.2 from BLProportion of pts achieving DAS ≤3.2Proportion of pts achieving DAS 6.01)Placebo-1.053732 5 mg BID-2.24762314 10 mg BID-2.49822517 Conclusions Across a range of BL disease activities, tofacitinib was consistently efficacious at both doses in reducing DAS28-3 (CRP) vs PBO. All groups showed numerical benefit in efficacy of 10 mg BID over 5 mg BID across all measures of DAS28-3 (CRP); the magnitude of benefit of 10 mg BID over 5 mg BID appeared to be independent of BL status. As expected, pts in the lowest quartile were more likely to achieve DAS28-3(CRP) ≤3.2 and