Efficacy of Upadacitinib Monotherapy for Active RA With Inadequate MTX Response

Hand xrays showing advanced rheumatoid arthritis
Hand xrays showing advanced rheumatoid arthritis
Upadacitinib monotherapy resulted in improvements in clinical and functional outcomes vs continuing methotrexate in a population of methotrexate inadequate-responders with active RA.

Upadacitinib monotherapy is a safe and efficacious potential treatment option for patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX) monotherapy, according to research published in The Lancet.

Data were evaluated in patients who participated in the SELECT-MONOTHERAPY trial, conducted at 138 sites across 24 countries. Initially, patients with active RA were randomly assigned 2:2:1:1 to either switch to once-daily upadacitinib monotherapy at 15 mg or 30 mg or continue with MTX therapy. At week 14, patients who were continuing MTX therapy switched to either 15 mg or 30 mg upadacitinib, which was randomly assigned at baseline. The primary study end points were the proportion of patients achieving American College of Rheumatology 20% Improvement (ACR) and the proportion of patients achieving low disease activity (defined by the 28-joint Disease Activity Score using C-reactive protein of 3.2 or lower), both at week 14.

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Of the 648 patients (overall mean age 54.3±12.1 years; disease duration 6.6±7.6 years) who were randomly assigned to treatment, 92% completed week 14 of the study. At 14 weeks, more patients in the upadacitinib group achieved the 2 primary end points than in the MTX group.

ACR20 response was achieved by 71%, 68%, and 41% of patients receiving 30 mg upadacitinib, 15 mg upadacitinib, and MTX, respectively (P <.0001 for both upadacitinib doses vs MTX). 28-joint Disease Activity Score using C-reactive protein of 3.2 or lower was achieved by 53%, 45%, and 19% of patients, respectively (P <.0001 for both upadacitinib doses vs MTX).

Additionally, more patients achieved ACR50 and ACR70 in the upadacitnib group vs MTX by week 2 and by week 14, 52% and 42% of the upadacitinib group 30 mg and 15 mg achieved ACR50 and 33% and 23% achieved ACR70, respectively, compared with 15% and 3% of those receiving MTX.

From baseline, mean improvements in all ACR core components were higher in those receiving upadacitinib. Adverse events occurred in 47% of MTX patients and 47% and 49% of 15 mg and 30 mg upadacitinib patients, respectively. Additionally, 3%, 5%, and 3% of patients, respectively, reported a serious adverse event.

Study limitations included a relatively short continued methotrexate-controlled period of just 14 weeks, but this was done to avoid undertreating patients in the MTX arm. Other limitations were a lack of inclusion of radiographic assessments and a lack of inclusion of an arm comparing MTX plus upadacitinib combination therapy with upadacitinib monotherapy.

The researchers concluded that “[t]his favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic disease-modifying antirheumatic drugs].”

This study was funded by AbbVie, Inc. Multiple researchers report relationships with the pharmaceutical industry. For a complete list of disclosures, please see the full text of the study online.


Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study [published online May 23, 2019]. Lancet. doi: 10.1016/S0140-6736(19)30419-2