Safety Profile of Upadacitinib Shows Drug May Increase Herpes Zoster Risk

Study evaluates the safety profile of upadacitinib at 15 mg and 30 mg once daily for patients with moderately to severely active rheumatoid arthritis.

Upadacitinib, a Janus kinase inhibitor, has shown promise treating rheumatoid arthritis (RA) but may increase the risk for herpes zoster and other conditions.

The study, conducted by investigators at Metroplex Clinical Research Center and published online in the Annals of the Rheumatic Diseases, evaluated the safety profile of upadacitinib at 15 mg and 30 mg once daily for patients with moderately to severely active RA.

The study authors analyzed treatment-emergent adverse events (TEAEs) and laboratory data from 5 randomized, placebo- or active-controlled phase 3 trials evaluating upadacitinib for patients with RA.

Exposure-adjusted event rates were shown for placebo (3 trials; 12/14 weeks), methotrexate (2 trials; mean exposure: 36 weeks), adalimumab (1 trial; mean exposure: 42 weeks), upadacitinib 15 mg (5 trials; mean exposure: 53 weeks), and upadacitinib 30 mg (4 trials; mean exposure: 59 weeks).

The study included 3834 patients administered 1 or more doses of upadacitinib 15 mg (n = 2630) or 30 mg (n = 1204), for a total of 4020.1 patient-years of exposure. The most common reported TEAEs were upper respiratory tract infections, nasopharyngitis, and urinary tract infections.

Rates of serious infections were similar between upadacitinib 15 mg and adalimumab, but these rates were higher compared to methotrexate. The rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both study groups compared to methotrexate and adalimumab. Further, rates of gastrointestinal perforations were higher in the upadacitinib 30 mg group.

The rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs), and venous thromboembolic events (VTEs) were similar across all the treatment groups.

“In the phase III clinical program for [rheumatoid arthritis], patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab,” the authors wrote. “Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab.”