Background/Purpose: In the SELECT-GCA phase 3 trial, treatment of patients with GCA with upadacitinib 15 mg (UPA15) demonstrated superior rates of disease remission, fewer disease flares, and reduced glucocorticoid (GC) use compared with placebo (PBO).1 The current study analyzed the 2-year outcomes in this trial.

Methods: SELECT-GCA included a 52-week randomized, PBO-controlled period 1 and a 52-week randomized, blinded extension period 2. Patients aged ≥ 50 years with a diagnosis of active GCA were randomized (2:1:1) to UPA15 or UPA 7.5 mg (UPA7.5) once daily with a 26-week GC taper or PBO with a 52-week GC taper. Period 2 involved patients in remission (absence of the signs or symptoms of GCA and adherence to the protocol-defined GC taper) for ≥ 24 consecutive weeks before the week 52 visit. Patients originally randomized to UPA7.5 or UPA15 were re-randomized (2:1) to continue the same dose of UPA or to switch to PBO in period 2. Patients originally randomized to PBO continued PBO. Efficacy outcomes were evaluated through week 104 and included remission (defined in period 2 as the absence of the signs or symptoms of GCA and no GC use for GCA), disease flare-related endpoints, and cumulative GC exposure. The safety analysis included all patients who received ≥ 1 dose of study drug in period 1 and continued the same treatment in period 2. Exposure-adjusted treatment-emergent adverse events (TEAEs) are reported through 2 years in this population.

Results: Of 428 patients randomized and treated in period 1, 181 (42%) achieved ≥ 24 consecutive weeks of sustained remission in period 1 and entered period 2 (PBO continuous, n = 34; UPA7.5 continuous, n = 30; UPA7.5 to PBO, n = 14; UPA15 continuous, n = 68; UPA15 to PBO, n = 35). Most (91%) of these patients completed the study, with 82% remaining on study drug. From week 52 through week 104, 68.6% of patients on continuous UPA15 maintained remission vs 28.6% who switched from UPA15 to PBO (Table 1). Patients on continuous UPA15 showed a 90% reduction in risk of disease flare from week 52 through week 104 compared with those who switched from UPA15 to PBO (Figure 1). The continuous UPA15 group also showed greater improvements across most other endpoints (Table 1), including those related to disease flare and cumulative GC exposure. Safety was generally similar for UPA and PBO groups among patients who continued the same treatment in period 2 (Table 2). Rates of serious TEAEs were lower for both UPA doses than PBO. Compared to PBO, UPA15 showed lower rates of serious infections but higher rates of herpes zoster and elevated creatine kinase. One venous thromboembolism event occurred with UPA15 in a patient with multiple risk factors and none in the other treatment groups. No major adverse cardiovascular events or deaths occurred in period 2 in any treatment group.

Conclusion: For patients with GCA receiving UPA15, continued use of UPA in those who were in remission for ≥ 24 weeks during period 1, rather than switching to placebo, was associated with maintenance of remission and an approximately 1-gram reduction in the cumulative use of GCs in period 2. In this population (mean age: 71 yrs), no new clinically significant safety risks were identified with use of UPA for 2 years.References1. Blockmans D, et al. NEJM. 2025.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-upadacitinib-in-giant-cell-arteritis-2-year-results-from-the-re-randomized-double-blind-select-gca-phase-3-trial/