Upadacitinib in Giant Cell Arteritis: Phase 3 Trial Results

Key Takeaways

• Upadacitinib 15 mg was associated with higher sustained remission at week 52 than placebo.
• Results for 15 mg also favored active treatment over placebo on sustained complete remission, time to flare, cumulative glucocorticoid exposure, and patient-reported outcomes.
• Safety outcomes over 52 weeks were similar across groups, no major adverse cardiovascular events occurred in the upadacitinib groups, and 7.5 mg was not superior to placebo on the primary end point.

The randomized, 2:1:1 phase 3 trial compared oral upadacitinib 15 mg or 7.5 mg once daily plus glucocorticoid taper with placebo plus glucocorticoid taper. A total of 209 patients received 15 mg, 107 received 7.5 mg, and 112 received placebo. Seventy percent of participants had new-onset disease, with the remainder enrolled with relapsing giant-cell arteritis. Glucocorticoid tapering differed by assignment, with 26 weeks in the upadacitinib arms and 52 weeks in the placebo arm. The primary endpoint was sustained remission at week 52, defined as absence of signs or symptoms of giant-cell arteritis from week 12 through week 52 with adherence to the protocol-specified taper.

For sustained remission at week 52, the 15-mg group had a 95% confidence interval of 39.6 to 53.2, compared with 20.6 to 37.5 for placebo. The 7.5-mg group reached 41.1%, with a 95% confidence interval of 31.8 to 50.4, and was not superior to placebo. In the hierarchically prespecified, multiplicity-controlled secondary analysis, results also favored 15 mg over placebo for sustained complete remission, time to disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes. The efficacy results favored 15 mg, while 7.5 mg did not show superiority on the primary endpoint.

Safety outcomes during the 52-week treatment period were similar in the upadacitinib and placebo groups. No major adverse cardiovascular events occurred in the upadacitinib groups during follow-up. Over 52 weeks, the primary remission endpoint favored 15 mg, while 7.5 mg was not superior to placebo.