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Tofacitinib or adalimumab versus placebo in rheumatoid arthritis

van Vollenhoven RF, Fleischmann R, Cohen S, et al. - The New England Journal of Medicine 2012; 367(6):508-19

The ORAL Standard trial is one of six studies conducted as part of the phase 3 research programme for the oral Janus kinase (JAK) inhibitor tofacitinib. This 12-month, phase 3 study compared the efficacy of tofacitinib with the TNF inhibitor adalimumab or placebo. Patients with active RA despite background methotrexate (MTX) were randomised to 5 or 10 mg tofacitinib twice daily, 40 mg adalimumab fortnightly, or placebo, which was switched to tofacitinib at month 3 in non-responders and month 6 for the remainder. At month 6, significantly more patients on active treatment achieved ACR 20 responses (placebo 28.3% vs tofacitinib 5 mg 51.5%; 10 mg 52.6%; adalimumab 47.2%) and DAS28-4(ESR)<2.6 (placebo 1.1% vs tofacitinib 5 mg 6.2%; 10 mg 12.5%; adalimumab 6.7%). Mean changes in HAQ-DI score at month 3 were at least twice as large for active treatments (placebo –0.24 vs tofacitinib 5 mg –0.55; 10 mg –0.61; adalimumab –0.49). Adverse events were more common with tofacitinib and adalimumab (placebo 47.2% vs tofacitinib 5 mg 52.0%; 10 mg 46.8%; adalimumab 51.5%); notable adverse events for tofacitinib included cytopenia, respiratory and urinary tract infections, gastrointestinal side effects and laboratory abnormalities. The study demonstrated that tofacitinib administered with background MTX is significantly superior to placebo and numerically similar to adalimumab in patients with rheumatoid arthritis receiving background MTX.