Phase 3 Upadacitinib Trial Shows Promising Results for Giant Cell Arteritis Treatment

In an interview with HCPLive, Daniel Blockmans, MD, PhD, discussed a phase 3, randomized, placebo-controlled trial that compared 2 doses of upadacitinib versus placebo among a cohort of patients with giant cell arteritis (GCA). The findings, presented at the 2024 European Congress of Rheumatology (EULAR) conference, focused on the first 52-week study period. The second study period is scheduled to conclude in March 2025.

In this first year, 428 patients were randomized to receive upadacitinib 15 mg (n = 209), upadacitinib 7.5 mg (n = 107), or placebo (n = 112). The placebo group received a 1-year taper of steroids, which is the standard of care for GCA. The upadacitinib groups received 6 months of steroids as background therapy.

The primary endpoint was the proportion of patients in sustained remission at 52 weeks. The results were positive, with the 15 mg upadacitinib group showing significantly better outcomes compared with the placebo group. Although the 7.5 mg upadacitinib group did not reach statistical significance, it was close and fell between the placebo and 15 mg groups. Additionally, 9 out of 11 multiplicity-controlled secondary endpoints with upadacitinib 15 mg were positive.

Blockmans noted he and his team were pleasantly surprised by the low incidence of side effects. There were only 2 cases of major cardiovascular events, both in the placebo group. Venous thromboembolism rates were balanced between groups, and there was no increase in cancer incidence, despite the elderly average patient age of 71.5 years.

While upadacitinib is not yet approved, he is hopeful for even better treatments. Current treatments like steroids and tocilizumab, an interleukin (IL)-6 inhibitor, can manage the clinical symptoms and acute phase response, but they do not cure the disease. He and his team aim to find drugs that have fewer side effects than steroids and a deeper impact on the underlying vasculitis.

The goal is to eliminate the smoldering vasculitis present in steroid or tocilizumab-treated patients, which can eventually lead to aortic dilation. This potential will be further investigated in the second year of the trial and other future studies that include imaging and reimaging to determine if the vasculitis has truly been resolved.

Disclosures: Blockmans has no relevant disclosures to report.