Upadacitinib vs Adalimumab in RA

July 24, 2019

The JAK1-selective inhibitor upadacitinib successfully improved the signs, symptoms and function of rheumatoid arthritis patients in a randomized clinical trial published this month in Arthritis and Rheumatology.

The JAK1-selective inhibitor upadacitinib successfully improved the signs, symptoms and function of rheumatoid arthritis patients in a randomized clinical trial published this month in Arthritis and Rheumatology.

The trial included 1,629 patients who were on methotrexate, but failed to achieve low disease activity or remission without safety or tolerability issues. But in this trial, with the addition of upadacitinib to treatment, upadacitinib improved the signs and symptoms of rheumatoid arthritis (RA) and significantly inhibited radiographic progression as compared to placebo, wrote the study authors who were led by Roy Fleischmann, M.D., of the University of Texas Southwestern Medical Center in Dallas.

"In this population of methotrexate inadequate responders with active RA, continuing methotrexate, with once daily upadacitinib 15 mg resulted in significantly greater improvements in clinical signs and symptoms, physical function and inhibition of radiographic progression versus placebo," the authors wrote.
Patients in this trial were randomized to receive either once-daily upadacitinib 15 mg, placebo, or the TNF blocker adalimumab at 40 mg. They were all on background methotrexate.

RELATED:  Upadacitinib Demonstrates Positive Outcomes as Monotherapy in Rheumatoid Arthritis

By week 12, 71 percent of patients met the primary endpoints of ACR20. And, 29 percent met the second primary endpoint of DAS28CRP of less than 2.6 as compared to placebo. Radiographic progression slowed and by week 26, patients on upadacitinib achieved low disease activity or remission in greater number than the other two groups.

While the rate of serious infections was comparable for both treatment groups, patients in the adalimumab group experienced more serious adverse events, some of which were so severe they discontinued treatment. However, the upadacitinib treatment group reported more cases of herpes zoster higher creatinine kinase levels.

Three malignancies, five major adverse cardiovascular events and four deaths were reported, but only among the adalimumab and placebo groups. Six venous thromboembolic events were reported among all three groups:  three for the adalimumab group, two for upadacitinib and one for the placebo group.

New treatments are needed, the authors wrote, because only one-third of patients on TNF inhibitors in combination with methotrexate achieve low disease activity or remission without safety or tolerability issues.

RELATED:  Adalimumab Biosimilar Performs Well in RA Trial

REFERENCE
Fleischmann R, Pangan AL, Song IH, 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."Arthritis and Rheumatology. July 9, 2019. DOI:https://www.ncbi.nlm.nih.gov/pubmed/31287230