A higher dose of upadacitinib was superior to adalimumab in patients with psoriatic arthritis, according to a study, but outcomes did not largely differ when a lower dose was administered.
“The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear,” the researchers explained.
The randomized, 24-week, phase 3 trial assigned patients 1:1:1:1 to oral upadacitinib (either 15 mg or 30 mg once daily), placebo, or subcutaneous adalimumab (40 mg every other week). The main outcome was American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12, comparing upadacitinib versus placebo; the upadacitinib versus adalimumab comparisons were secondary outcomes.
Final analysis included 1,704 patients in all four arms. At week 12, the proportions of patients who attained an ACR20 response were: 15 mg upadacitinib, 70.6%; 30 mg upadacitinib, 78.5%; placebo, 36.2% (P<0.001 for both upadacitinib doses vs placebo); and adalimumab, 65.0%. When comparing 15 mg upadacitinib versus adalimumab, the between-groups difference was 5.6 percentage points (95% confidence interval [CI], –0.6 to 11.8), and for 30 mg upadacitinib, 13.5 percentage points (95% CI, 7.5-19.4). For 12-week ACR20 response, the 30 mg upadacitinib dose was superior to adalimumab, with both doses considered noninferior to adalimumab.
At 24 weeks, the incidence of adverse events was highest in the 30 mg upadacitinib group (72.3%), followed by the 15 mg upadacitinib (66.9%), adalimumab (64.8%), and placebo (59.6%) groups. The rates of serious infections were: 30 mg upadacitinib, 2.6%; 15 mg upadacitinib, 1.2%; adalimumab, 0.7%; and placebo, 0.9%. The rates of hepatic disorders in the low- and high-dose upadacitinib groups were 9.1% and 12.3%, respectively, but the rate of grade 3 increases in aminotransferase levels was 2% or less in all groups.
The study was published in the New England Journal of Medicine.
“The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo,” the researchers concluded.