ORAL Determined Tofacitinib Monotherapy, Tofacitinib with Methotrexate, and Adalimumab with Methotrexate in RA Patients

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ORAL Determined Tofacitinib Monotherapy, Tofacitinib with Methotrexate, and Adalimumab with Methotrexate in RA Patients

Tofacitinib plus Methotrexate combination treatment was non-inferior to Adalimumab plus Methotrexate combination treatment among RA patients who showed an inadequate response to methotrexate, findings from a recent trial published in “The Lancet” Journal. In addition, the Tofacitinib monotherapy failed to show non-inferiority to either combination.

Rheumatoid arthritis (RA) is a persistent inflammatory disease that influences about 1% of the world's population. This severe condition is managed by certain Conventional and Biological Disease-modifying anti-rheumatic drugs (cDMARDs & bDMARDs). The bDMARDs are prescribed when patients fail to respond to cDMARDs. One such bDMARDs is tofacitinib. Tofacitinib is an inhibitor of Janus kinases. This is an approved drug for RA treatment.  The efficacy and safety of Tofacitinib were investigated through ORAL (Oral Rheumatoid Arthritis) trials. Now scientists aimed to determine the comparative efficacy of tofacitinib monotherapy, adalimumab plus methotrexate, and tofacitinib plus methotrexate for rheumatoid arthritis treatment among patients having an inadequate response to methotrexate (cDMARDs) in the past. They conducted a 1 year, double-blind, non-inferiority, head-to-head, phase 3b/4, randomized controlled Oral Rheumatoid Arthritis trial (ORAL) trial for evaluation.

A total of 1146 patients of age 18 or older with an active rheumatoid arthritis despite methotrexate therapy involved in the study. The patients were categorized randomly during the treatment. Out of 1146 patients,384 received tofacitinib monotherapy (5 mg twice daily orally); 376 received tofacitinib plus methotrexate 5 mg twice daily orally) and 386 received adalimumab plus methotrexate treatment (40 mg every other week subcutaneously). The whole trial was conducted at 194 centres in 25 countries. Eligible patients received live zoster vaccine at investigators' discretion. The patients who obtained 50% of an American College of Rheumatology response (ACR50) at 6 months in the full analysis set was considered as the primary endpoint. A full analysis set involved patients who were randomly selected to a group and obtained at least one dose of the study treatment. The trail group's non-inferiority was exhibited if the lower bound of the 98·34% CI of the difference between comparators was greater than −13·0%.

One forty seven patients with tofacitinib monotherapy, 173 patients with tofacitinib plus methotrexate, and 169 patients with adalimumab plus methotrexate were successful to achieve ACR50 response at 6 months. Some of the patients, 23 of tofacitinib monotherapy group, 26 of tofacitinib plus methotrexate group and 36 of adalimumab plus methotrexate group discontinued the treatment due to adverse events. Two of the patients who were receiving tofacitinib monotherapy died. However, no new or unexpected safety issue noticed during trial up to 1 year. The non-inferiority between groups were noticed for tofacitinib plus methotrexate versus adalimumab plus methotrexate only (difference 2% [98·34% CI −6 to 11])


The Lancet

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Original title of article:

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


Roy Fleischmann et al.

Therapeutic, Tofacitinib, Adalimumab, Rheumatoid Arthritis, cDMARDs & bDMARDs, Double blind, Randomised controlled, Comparative, Efficacy, Safety, Oral
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