medwireNews: Rheumatoid arthritis (RA) patients treated with the Janus kinase (JAK)1 selective inhibitor upadacitinib experience greater improvement in the signs and symptoms of disease than those given placebo or adalimumab, indicate findings from the SELECT-COMPARE trial.
In the phase III study, 1629 patients with active RA despite treatment with methotrexate were randomly assigned to receive upadacitinib 15 mg/day, placebo, or adalimumab 40 mg every 2 weeks, all given alongside stable background methotrexate.
Roy Fleischmann (Metroplex Clinical Research Center, Dallas, Texas, USA) and co-investigators demonstrated that the 651 participants treated with upadacitinib had significantly higher rates of the co-primary endpoints of ACR20 response and remission according to a DAS28-CRP score of less than 2.6 points at week 12 than the 651 given placebo, at 71% versus 36%, and 29% versus 6%, respectively.
ACR20 response rates at week 12 were numerically higher among upadacitinib-treated patients compared with the 327 given adalimumab, at 71% versus 63%. A significantly higher number of patients treated with upadacitinib versus placebo or adalimumab achieved an ACR50 response (45 vs 15 and 29%, respectively) or a DAS28-CRP score of 3.2 points or lower (45 vs 14 and 29%, respectively).
[The SELECT-COMPARE results] at least seem to suggest that upadacitinib 15mg plus methotrexate is superior to adalimumab. That's a key study.
Patients in the upadacitinib arm also had significantly greater improvements in quality of life, fatigue, and duration of morning stiffness from baseline to week 12 than those in the placebo or adalimumab arms. Radiographic progression – measured by the average mTSS score at week 26 – was significantly reduced among participants treated with upadacitinib versus placebo, but not versus adalimumab.
Fleischmann and team say that the safety profile of upadacitinib in SELECT-COMPARE “was generally comparable to that of adalimumab,” but rates of herpes zoster, creatinine phosphokinase elevation, and lymphopenia were higher with the JAK1 inhibitor.
Adverse events occurred in 64.2% of patients given upadacitinib, 53.2% of those given placebo, and 60.2% of those in the adalimumab group. A total of 0.8%, 0.5%, and 0.3% of patients, respectively, experienced herpes zoster infection, and the corresponding mean levels of creatinine phosphokinase and lymphocyte counts were 83.92, 0.87, and 24.17 U/L and 0.06, 0.02, and 0.34 x 109/L.
“Overall, upadacitinib 15mg demonstrated a favorable benefit:risk profile for the treatment of RA,” write the study authors in Arthritis & Rheumatology.
They conclude that integrated analysis of all the phase III SELECT trials will provide “further understanding of the potential use and safety of upadacitinib in RA patients.”
Click through for a guide to the trials of JAK inhibitors in RA, including the SELECT trials
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Arthritis Rheumatol 2019; doi:10.1002/art.41032