Title: Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial
Fleischmann, R et al.
What You Need to Know:
In patients with rheumatoid arthritis who did not previously respond to treatment with methotrexate adequately, combination therapy of tofacitinib plus methotrexate was found to be non-inferior to therapy of adalimumab plus methotrexate, while treatment with tofacitinib alone was not found to be non-inferior to either combination.
- Double-blind, head-to-head, non-inferiority phase 3b/4 study compared the efficacy of tofacitinib + methotrexate, adalimumab + methotrexate, and tofacitinib alone for the treatment of rheumatoid arthritis in patients who failed methotrexate therapy previously
- 1146 patients were randomized (1:1:1) to receive 5mg tofacitinib twice daily (n=384), 5mg tofacitinib twice daily + methotrexate (n=376), or 40mg adalimumab administered subcutaneously every other week + methotrexate (n=386)
- Primary endpoint: percent of patients who achieved a ≥50% American College of Rheumatology response (ACR50) at month 6 (analyzed in all patients who received ≥1 dose of study treatment)
- Non-inferiority between groups was shown if the lower bound of the 98.34% CI of the difference between comparators was larger than -13.0%
- ACR50 response at month 6: achieved by 38% of the tofacitinib group (147/384), 46% of tofacitinib + methotrexate group (173/376), and 44% of adalimumab + methotrexate group (169/386)
- Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and methotrexate (difference 2% [98.34% CI -6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and methotrexate (-6[-14 to 3]) or tofacitinib and methotrexate (-8[-16 to 1])
- Discontinuation due to adverse events occurred in 6% of patients receiving tofacitinib monotherapy, 7% of patients receiving tofacitinib + methotrexate, and 9% of patients receiving adalimumab + methotrexate
- Death occurred in 1% of patients receiving tofacitinib monotherapy