The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.
Prof. Josef S. Smolen
“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.
The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.
Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.
An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.
“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.
Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).
Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.
“This 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] DMARDs,” the authors wrote.
The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.
SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2