Background/Purpose: Tofacitinib is a novel oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for RA. This post-hoc analysis of the Phase 3 active-controlled randomized ORAL Standard trial (NCT00853385) determined the relationship between changes in the Disease Activity Score (28 joints, 4 components, ESR; DAS28) during the first 3 months (mo) of treatment with tofacitinib or adalimumab (ADA), and the likelihood of achieving low disease activity (LDA) at Mo 6 or Mo 12 in patients (pts) with RA.

Methods: Pts on stable background methotrexate (MTX) were randomized 4:4:4:1:1 to one of five sequences: tofacitinib 5 mg twice daily (BID); 10 mg BID; ADA 40 mg sc biweekly (q2w); placebo (PBO) advanced to tofacitinib 5 mg BID; or PBO advanced to 10 mg BID. All pts self-administered injections q2w (ADA or PBO). Pts on PBO advanced to tofacitinib at Mo 6, or at Mo 3 if they did not show ≥20% reduction from baseline (BL) in swollen/tender joint counts.

Results: Overall, 717 pts were treated. Primary results have been reported previously.¹ Mean BL DAS28 values across sequences were 6.4-6.6. Tofacitinib 5 and 10 mg BID and ADA all showed statistical superiority to PBO at Mo 3 and Mo 6, and achieved numerically similar responses, including rates of LDA (DAS28 ≤3.2) (Table). In the current analysis of pts with a DAS28 improvement from BL <0.6 by Mo 1, less than 5% receiving tofacitinib 5 mg BID and approximately 10% receiving tofacitinib 10 mg BID achieved LDA at Mo 12. In pts with a DAS28 improvement from BL <0.6 by Mo 3, none achieved LDA at Mo 6 or Mo 12 on either dose of tofacitinib, while approximately 10% (n=2) of ADA pts with DAS28 improvement <0.6 by Mo 3 achieved LDA at Mo 12 (Table).

Conclusion: LDA rates were similar between tofacitinib and ADA. In this post-hoc analysis of the ORAL Standard study, failure to achieve ≥0.6 improvement from baseline in DAS28 within the first 3 months of tofacitinib treatment was predictive of a low probability of achieving LDA at 1 year.

Reference:

   1.   van Vollenhoven RF et al. Arthritis Rheum 2011; 63: S153.