Guselkumab Falls Short in Phase 2 Giant Cell Arteritis Trial

Key Takeaways

• Week 28 glucocorticoid-free remission was observed more often with guselkumab than placebo, but the primary endpoint was not met.
• Flare-related outcomes and time-to-first-flare findings did not separate the study groups.
• Adverse events through week 60 were common in both groups, and the authors concluded that the findings did not support guselkumab for GCA.

Glucocorticoid-free remission at week 28 was seen in 40% of patients assigned to guselkumab and 33% assigned to placebo in a phase 2 randomized placebo-controlled trial in giant cell arteritis. The comparison enrolled adults with new-onset or relapsing disease, and both groups received background glucocorticoids with a protocol-defined taper through week 26. The primary endpoint was remission without glucocorticoids at week 28 after the taper period. The findings did not show a statistically significant week 28 remission advantage for guselkumab.

Randomization used a 2:1 ratio, with 35 participants receiving guselkumab and 18 receiving placebo. The study was double-blind and limited enrollment to adults aged 50 years or older with new-onset or relapsing GCA. All enrolled patients were White, 70% were female, the mean age was 71.5 years, and disease status was 60% new-onset and 40% relapsing. Both groups received background glucocorticoids with tapering through week 26, and remission was assessed as glucocorticoid-free status at week 28.

Beyond the remission endpoint, 31% of the guselkumab group and 39% of the placebo group had a GCA flare or discontinued because disease worsened. Median time to first flare through week 28 was not estimable with guselkumab, with a 90% CI ranging from 27.7 weeks to not estimable. In the placebo arm, the median time to first flare was 29.7 weeks, with a 90% CI from 20.1 weeks to not estimable. These secondary outcome measures were consistent with the primary remission analysis. Investigators reported a P value of .64, and the flare analyses also did not separate the groups.

Through week 60, adverse events were reported in 97% of patients assigned to guselkumab and 94% assigned to placebo. Worsening GCA was listed separately from the other common adverse events across both study groups. Aside from worsening GCA, COVID-19 infection was the most common named event, affecting 23% of the guselkumab group and 28% of placebo recipients. Headache was also frequent, occurring in 17% of patients given guselkumab and 39% given placebo. The authors concluded that the primary endpoint was not met and that the results did not support guselkumab for treatment of giant cell arteritis.