A phase 2, randomised, placebo-controlled study of guselkumab in adults with new-onset or relapsing giant cell arteritis.

Guselkumab, a monoclonal antibody, selectively targets the p19 subunit of interleukin-23. This randomised, double-blind, placebo-controlled, phase 2 study evaluated guselkumab vs placebo for the treatment of giant cell arteritis (GCA). Patients ≥50 years of age with new-onset or relapsing GCA were randomised 2:1 to guselkumab or placebo. Both arms received background glucocorticoid (GC) therapy, with a protocol-defined taper through week 26. The primary endpoint was the proportion of patients achieving GC-free remission at week 28. Thirty-five patients were randomised to receive guselkumab and 18 to receive placebo. All patients were White, 70% were female, and the mean age was 71.5 years; 60% had new-onset and 40% had relapsing GCA. At week 28, 40% (14/35) and 33% (6/18) of patients in the guselkumab and placebo groups, respectively, achieved GC-free remission (P = .64), whereas 31% (11/35) and 39% (7/18) had experienced a GCA flare or discontinued due to worsening GCA. Median time to first GCA flare through week 28 was not estimable (NE) in the guselkumab group (90% CI: 27.7-NE) and 29.7 weeks (90% CI: 20.1-NE) in the placebo group (P = .64). Through week 60, 97% (34/35) and 94% (17/18) of patients in the guselkumab and placebo groups, respectively, had adverse events (AEs); the most common AEs, aside from worsening of GCA (49% and 56%, respectively), were COVID-19 infection (23% and 28%) and headache (17% and 39%). The study's primary endpoint (GC-free remission) was not met; results do not support the use of guselkumab in the treatment of GCA.