Oral upadacitinib (Rinvoq), a Janus kinase (JAK) inhibitor, has shown success in treating giant cell arteritis (GCA) by allowing patients to withdraw from corticosteroid use, according to phase III trial results. The SELECT-GCA study (NCT03725202) revealed that 46.4% of patients receiving upadacitinib at 15 mg/day achieved clinical remission without needing rescue steroids during weeks 12-52, compared to 29.0% in the placebo group with an extended steroid tapering schedule. This study suggests a potential new targeted therapy with a favorable benefit-risk profile for GCA patients.
SELECT-GCA Trial Details
The multinational SELECT-GCA study, initiated in early 2019, enrolled 428 patients across 24 countries. Participants were randomized in a 2:1:1 ratio to receive upadacitinib at 15 mg/day, 7.5 mg/day, or placebo for 52 weeks. Steroids were tapered to zero over 26 weeks in the upadacitinib arms, while the placebo group's tapering extended to 52 weeks. The primary endpoint was "sustained remission," defined as the absence of GCA symptoms from weeks 12-52 and adherence to the tapering schedule. Secondary endpoints included a stricter "complete remission" standard, incorporating normalization of erythrocyte sedimentation rate and C-reactive protein levels.
Efficacy and Safety
The 15-mg/day dose of upadacitinib demonstrated superiority over placebo across nearly all endpoints. "Complete remission" was achieved by 37.1% of the 15-mg/day group, 26.2% of the 7.5-mg/day group, and 16.1% of the placebo group (P < 0.0001 for the high dose vs placebo). Upadacitinib was superior to placebo for nine of eleven secondary outcomes, with only patient global satisfaction failing to show a significant advantage. Some 34% of patients on 15 mg/day had at least one flare, compared with 56% in the placebo group.
Safety findings were generally unremarkable, with no statistically significant differences in adverse event rates among the groups. Serious infections were numerically more common in the placebo group. Anemia was observed more frequently in the higher upadacitinib group (8.4 per 100 patient-years) compared to the lower dose and placebo groups (3.4 and 3.2, respectively), though this difference was not statistically significant.
Current Treatment Landscape
Corticosteroids remain the primary treatment for GCA, but their long-term use is limited by adverse effects. Tocilizumab (Actemra) is currently the only other approved targeted therapy for GCA. Upadacitinib, if approved for this indication, would offer an oral alternative, potentially improving long-term management and reducing steroid-related side effects. AbbVie, the manufacturer of upadacitinib, submitted regulatory applications to the FDA and EMA for the GCA indication in July.
Peter Merkel, MD, MPH, of the University of Pennsylvania, noted that having a safer targeted therapy for long-term treatment is imperative, given the adverse effects associated with prolonged steroid use.
