Upadacitinib versus Abatacept: How Do These Rheumatoid Arthritis Drugs Compare?

A study that put rheumatoid arthritis drugs upadacitinib and abatacept head-to-head yielded mixed results: upadacitinib was associated with better disease outcomes, but at the cost of more serious adverse events (AEs). The comparison of oral selective Janus kinase inhibitor upadacitinib to T-cell costimulation modulator abatacept was done in the form of a 24-week, phase 3, double-blind, controlled trial. Patients were randomized 1:1 to receive either once daily 15 mg upadacitinib (orally) or abatacept (intravenously); both drugs were given in combination with stable synthetic disease-modifying antirheumatic drugs. the main outcome was 12-week change in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP); scores ranged from 0 to 9.4, with higher scores indicative of more disease activity. Additional outcomes were the superiority of upadacitinib over abatacept measured by the change from baseline in the DAS28-CRP and the percentage of patients achieving clinical remission, defined by a DAS28-CRP <2.6. There were 303 patients in the upadacitinib group and 309 in the abatacept group. At baseline, DAS28-CRP values were 5.70 in the upadacitinib group and 5.88 in the abatacept group; at week 12, the mean changes were −2.52 and −2.00, respectively (difference, −0.52 points; 95% confidence interval [CI], −0.69 to −0.35; P<0.001 for noninferiority; P<0.001 for superiority). A significantly greater proportion of patients in the upadacitinib group achieved remission compared to the abatacept group (30.0% vs. 13.3%; difference, 16.8 percentage points; 95% CI, 10.4-23.2; P<0.001 for superiority). Serious AEs in the upadacitinib group during treatment included death (n=1), nonfatal stroke (n=1), and venous thromboembolic events (n=2). The upadacitinib group had a greater proportion of patients with elevated hepatic aminotransferase levels compared to the abatacept group. The study was published in The New England Journal of Medicine. “Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis,” the study authors concluded.