Written by Kevin Liu
Spoon Feed
Upadacitinib 15 mg plus a 26-week steroid taper induced higher rates of sustained remission in giant-cell arteritis (GCA) than placebo plus a 52-week steroid taper.
JAK up the GCA game – upadacitinib had swifter remission
GCA remains a challenging disease to manage due to frequent relapses and glucocorticoid dependence, which can oftentimes cause life-altering complications including diabetes, bone density loss, zoster activation, myopathy, and thromboembolic risk. This study offers promise for a steroid-sparing approach using a Janus kinase (JAK) inhibitor. While tocilizumab is the only approved agent beyond steroids, more patients in the treatment arms of that trial dropped out due to side effects. This phase 3 RCT (SELECT-GCA) enrolled 428 patients with new-onset or relapsing GCA, randomized 2:1:1 to upadacitinib 15 mg, 7.5 mg (both with 26-week steroid tapers), or placebo (52-week taper). At week 52, 46.4% of patients on 15 mg upadacitinib achieved sustained remission versus 29% on placebo (P = 0.002), with significantly better results across all key secondary outcomes: complete remission (37.1% vs. 16.1%), flare risk (34.3% vs. 55.6%), and cumulative steroid exposure (median 1615 mg vs. 2882 mg). Safety signals were similar between arms, with no increase in major cardiovascular events or malignancy in the upadacitinib groups; however, this study is confounded by high discontinuation rates (~26% in the treatment arm, ~37% in placebo), likely influenced by the trial coinciding with the COVID-19 pandemic. Long-term safety, particularly cardiovascular risk, needs further evaluation.
How does this change my practice?
If the FDA approves this indication, upadacitinib 15 mg would become a viable option for patients with new-onset or relapsing GCA, particularly our elderly cohort at high risk for glucocorticoid complications or refractory disease. While safety appears comparable in the short term, I would remain cautious and monitor closely for zoster, myopathy, and thromboembolic risk. I am curious if the high discontinuation rates would persist in our post-COVID healthscape.
Source
A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. N Engl J Med. 2025 Apr 2. doi: 10.1056/NEJMoa2413449. Epub ahead of print. PMID: 40174237
