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, Mysler E, Hall S, Kivitz A, Moots R, Luo Z, DeMasi R, Soma K, Zhang R, Takiya L, Tatulych S, Mojcik C, Krishnaswami S, Menon S, Smolen J, on behalf of the ORAL Strategy investigators. - Lancet 2017 [Epub ahead of print] DOI 10.1016/S0140-6736(17)31618-5
In this first head-to-head non-inferiority trial assessing a JAKi ± MTX directly compared with a TNFi + MTX in patients with RA, tofacitinib (TOF) + MTX showed non-inferiority to adalimumab (ADA) + MTX. Non-inferiority was not shown for TOF monotherapy versus TOF + MTX, or versus ADA + MTX.
In this 52-week study, MTX-inadequate responder (IR) patients were randomised 1:1:1 to receive TOF 5 mg BID monotherapy, TOF 5 mg BID + MTX or ADA 40 mg every other week + MTX. The primary endpoint, ACR50 response at 6 months, was achieved in 38% of TOF monotherapy patients, 46% of TOF + MTX patients and 44% of ADA + MTX patients. This response was continued in all groups through Month 12; a similar trend was also seen for ACR20 and ACR70. Low disease activity and clinical remission rates were similar between combination arms, and were higher than for TOF monotherapy.
Although more patients developed SAEs in the TOF groups, discontinuations due to AEs were higher in the ADA + MTX group (10%) than in either TOF group (6%; mono- and 7% combo-). There were no new or unexpected safety issues for any of the groups.
This study provides evidence that, as proposed by the updated EULAR recommendations,1 adding either a bDMARD or a targeted synthetic DMARD can be considered as treatment options in patients with RA and an inadequate response to MTX.