Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial

The Lancet 2013; 381(9865):451-60

The ORAL Step trial is one of six studies conducted as part of the phase 3 research programme for the oral Janus kinase (JAK) inhibitor tofacitinib. This 6-month, double-blind, parallel-group phase 3 study investigated the efficacy and safety of tofacitinib in adults with moderate to severe rheumatoid arthritis (RA) with an inadequate response to tumour necrosis factor (TNF) inhibitors. Patients were randomised to 5 or 10 mg tofacitinib twice daily or placebo, which was switched to tofacitinib after month 3. Both tofacitinib doses produced rapid, significant and clinically meaningful improvements in signs and symptoms compared with placebo over 6 months. Time to onset of significant ACR 20 response was 2 weeks for both doses, and about twice as many patients on tofacitinib achieved ACR 20 responses at month 3 (placebo 24.4% vs tofacitinib 5 mg 41.6%; 10 mg 48.1%). At month 3, tofacitinib produced significantly greater improvements from baseline in HAQ-DI score (placebo –0.18 vs 5 mg –0.43; 10 mg –0.46) and larger proportions of patients had achieved DAS-28(ESR)<2.6 with tofacitinib (placebo 1.7% vs 5 mg 41.6%; 10 mg 48.1%). The study found diarrhoea, nasopharyngitis, headache and urinary tract infections were the most common side effects in the tofacitinib groups, and nausea in the placebo group. This study indicates that tofacitinib could be an effective treatment option in RA patients with an inadequate response to TNF inhibitors.