In patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate, upadacitinib is superior to adalimumab and placebo for improving signs, symptoms, and physical function, according to study results published in Arthritis & Rheumatology.

The results did, however, find that upadacitinib, a Janus Kinase 1-selective inhibitor,  had higher rates of herpes zoster and creatine phosphokinase (CPK) elevations compared with adalimumab.

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The study included patients with RA who had an inadequate response to methotrexate (n=1629). Patients were randomly assigned 2:2:1 to once-daily upadacitinib 15 mg, placebo, or adalimumab 40 mg, all with stable background methotrexate. The primary outcomes were American College of Rheumatology 20 response criteria (ACR20) and Disease Activity Score for 28-joints (DAS28CRP) <2.6 compared with placebo at week 12. At week 26, the researchers evaluated inhibition of radiographic progression.

At week 12, 71% of patients taking upadacitinib achieved ACR20 compared with 36% of patients taking placebo (P ≤.001). In addition, 29% of patients taking upadacitinib achieved DAS28CRP <2.6 compared with 6% of patients taking placebo (P ≤.001).

At week 26, the results indicated that more patients taking upadacitinib achieved low disease activity or remission compared with patients taking placebo or adalimumab (P ≤.001).

The researchers found that patients taking upadacitinib had less radiographic progression compared with placebo, and radiographic progression was observed in fewer patients taking upadacitinib overall (P ≤.001).

The rate of adverse events (AEs) including serious infections was comparable for upadacitinib and adalimumab through week 26. Patients taking adalimumab had the highest percentage of serious AEs and AEs leading to discontinuation. Patients taking upadacitinib had the highest percentage of herpes zoster and creatine phosphokinase (CPK) elevations.

There were three malignancies, five major adverse cardiovascular events, and four deaths, but none of these occurred in patients taking upadacitinib. Of six reported venous thromboembolic events, one occurred on placebo, two occurred on upadacitinib, and three occurred on adalimumab.

“Integrated analyses of all five pivotal phase 3 trials will further understanding of the potential use and safety of upadacitinib in RA patients,” the researchers wrote.

Disclosures: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Fleischmann R, Pangan AL, Song I, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase 3, double-blind, randomized controlled trial [published online July 9, 2019]. Arthritis Rheumatol. doi:10.1002/art.41032