Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for RA. This analysis evaluated the rates of remission across five tofacitinib Phase 3 RA trials based on various established and new remission criteria including the ACR/EULAR criteria.

Methods: We analyzed the data from five Phase 3 RA trials of tofacitinib monotherapy (ORAL Solo) or tofacitinib with background DMARD (ORAL Step, Scan, Sync and Standard) and compared remission rates as defined by various remission criteria: a) DAS28-4(ESR) <2.6 (co-primary endpoint in all five Phase 3 studies); b) DAS28-3(CRP) <2.6; c) CDAI ≤2.8; d) index-based ACR/EULAR criteria (SDAI ≤3.3); and e) Boolean-based ACR/EULAR criteria.¹ Remission rates were calculated under each set of criteria for each treatment sequence: tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo (PBO) to 5 mg BID, and PBO to 10 mg BID; PBO sequences were pooled. ORAL Standard also included adalimumab 40 mg sc every 2 weeks as an active control. All trials had an initial PBO period of 3 or 6 months. Here, 3-month LOCF data are presented to illustrate results.

Results: Despite the short treatment duration, rates of remission were 5-30% with tofacitinib treatment (Table). Remission rates were numerically greater for both tofacitinib doses versus placebo, and rates for tofacitinib 10 mg BID were generally greater than with 5 mg BID. Across trials, the DAS28-3(CRP)-based criteria generated markedly higher remission rates compared with other remission criteria.

Conclusion: Tofacitinib was effective in reaching treatment target^2-4 and inducing remission after 3 months of treatment using various established and new remission criteria including the ACR/EULAR index- and Boolean-based criteria. Remission rates were generally greater with tofacitinib 10 mg BID compared with 5 mg BID.

References

   1.   Felson DT et al.  Arthritis Rheum 2011; 63: 573-586.

   2.   Singh JA et al.  Arthritis Care Res (Hoboken ) 2012; 64: 625-639.

   3.   Smolen JS et al.  Ann Rheum Dis 2010; 69: 964-975.

   4.   Smolen JS et al.  Ann Rheum Dis 2010; 69: 631-637.