Tofacitinib/Methotrexate Combination Shows Non-Inferiority in Rheumatoid Arthritis

Combination treatment with tofacitinib and methotrexate (MTX) was successful in a phase 3b/4 clinical trial for the treatment of rheumatoid arthritis (RA).

The randomized, controlled, double-blind, head-to-head, non-inferiority ORAL Strategy trial was designed to examine the comparative efficacy of tofacitinib monotherapy, tofacitinib plus MTX, and adalimumab plus MTX in patients with RA who previously had an inadequate response to MTX therapy.

Included in the study were 1146 patients 18 years and older with active RA despite treatment with MTX.

The participants were randomized to receive either 5 mg of oral tofacitinib monotherapy twice-daily, 5 mg of oral tofacitinib twice daily plus MTX, or 40 mg of subcutaneous adalimumab bi-weekly plus MTX.

The primary endpoint was the proportion of patients who attained an American College of Rheumatology response of at least 50% (ACR50) at 6 months in the full analysis set.

The results of the study, published in The Lancet, showed that 28% of patients in the tofacitinib monotherapy arm achieved an ACR50 response at 6 months and 44% of patients in the adalimumab and MTX arm.

Non-inferiority was declared for tofacitinib and MTX versus adalimumab and MTX, but not for tofacitinib monotherapy versus either adalimumab and MTX or tofacitinib and MTX, according to the study.

Overall, 6% of patients in the tofacitinib monotherapy arm, 7% in the tofacitinib plus MTX arm, and 9% in the adalimumab plus MTX arm discontinued treatment because of adverse events. Two patients in the tofacitinib monotherapy arm died. There were no new or unexpected safety issues for either treatment—–up to 1 year––reported from the study.

“Tofacitinib and methotrexate combination therapy was non-inferior to adalimumab and methotrexate combination therapy in the treatment of rheumatoid arthritis in patients with an inadequate response to methotrexate in this trial,” the authors concluded. “Tofacitinib monotherapy was not shown to be non-inferior to either combination.”