Phase III SELECT-GCA Trial Results Lead to FDA Approval of Rinvoq for Giant Cell Arteritis
Rinvoq (upadacitinib) becomes the first oral JAK inhibitor approved by the FDA for the treatment of giant cell arteritis in adults, following robust data from the Phase III SELECT-GCA trial demonstrating its efficacy in achieving sustained remission and reducing glucocorticoid exposure.
Credit: Yurii Kibalnik | stock.adobe.com
The FDA has approved AbbVie’s Rinvoq (upadacitinib) 15 mg once daily for the treatment of adults with giant cell arteritis (GCA) based on findings from the pivotal Phase III SELECT-GCA trial (NCT03725202).1-3 The regulatory action marks the ninth overall approval for Rinvoq across rheumatology, gastroenterology, and dermatology and makes it first oral Janus Kinase (JAK) inhibitor indicated for the treatment of GCA in adult patients.
The only other FDA-approved treatment for GCA is the interleukin-6 receptor inhibitor Actemra (tocilizumab). Glucocorticoids are the primary treatment option for GCA but increase the risk of toxic adverse effects (AEs).
"Glucocorticoids remain a mainstay of treatment of GCA but lead to substantial drug-associated toxicities. Additionally, relapse remains common for patients with this disease," SELECT-GCA trial investigator Peter A. Merkel, MD, MPH, chief of rheumatology at the University of Pennsylvania, Philadelphia, said in a press release. "We now have a new option to treat GCA. The results of this clinical trial show that (Rinvoq) offers patients the chance to reach sustained remission."1
Rinvoq is a JAK inhibitor that modulates the signaling pathway at the point of JAKs to inhibit the phosphorylation and activation of signal transducers and activators of transcription.4 The drug is also approved to treat moderate-to-severe rheumatoid arthritis; active psoriatic arthritis; active ankylosing spondylitis; active non-radiographic axial spondylarthritis; moderate to severe ulcerative colitis; and moderate-to-severe Crohn disease.
Trial Design
The multicenter, randomized, double-blind placebo-controlled SELECT-GCA trial analyzed the safety and efficacy of Rinvoq in 428 adult patients with GCA. The trial was designed with two periods, one of which compared the efficacy and safety of Rinvoq combined with a 26-week corticosteroid taper regimen vs. placebo in combination with a 52-week corticosteroid taper regimen. The second period analyzed the safety and efficacy of either continuing or withdrawing Rinvoq while maintaining remission in those who experienced sustained remission in the trial’s first period.
Investigators randomly assigned 428 patients with new-onset or relapsing GCA in a 2:1:1 ratio to receive oral Rinvoq 15 mg (n = 209) or 7.5 mg (n = 107) once daily combined with the 26-week glucocorticoid taper, or placebo (n = 112) plus the 52-week glucocorticoid taper. The trial’s primary endpoint was sustained remission at week 52, which was determined by prevalence of signs or symptoms of GCA from week 12 to week 52, as well as adherence to protocol-specified glucocorticoid taper.
Manifestations of giant-cell arteritis include headaches, pain or tenderness in the scalp or temple, jaw claudication, impaired vision, and ischemic complications. Polymyalgia rheumatica has also been linked to GCA with many patients experiencing overlapping symptoms, according to the investigators. The trial’s key secondary endpoints included sustained complete remission, time to disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes.
Results show that 46.4% of patients administered the 15 mg dose of Rinvoq achieved sustained remission at week 52 (95% confidence interval [CI], 39.6 to 53.2) compared to 29.0% of patients administered placebo (95% CI, 20.6 to 37.5; P=0.002). Notably, the Rinvoq 7.5 mg dose did not achieve superiority over placebo in producing sustained remission at week 52 (41.1% [95% CI, 31.8 to 50.4]).
The 15 mg dosing cohort also achieved superiority to placebo in the hierarchically prespecified and multiplicity-controlled key secondary endpoints. In terms of safety, AEs during the 52-week treatment period were similar among the cohorts, with no significant cardiovascular AEs reported in the Rinvoq cohort despite cardiovascular risk being a concern with JAK inhibitors, according to the trial investigators.
"This FDA approval will now provide an alternative treatment option that can offer patients with GCA the possibility of tapering off steroids and achieving sustained remission," said Roopal Thakkar, MD, executive vice president, research and development, chief scientific officer, AbbVie. "With this new indication for Rinvoq, we are underscoring AbbVie's commitment to exploring how we can identify and address unmet needs for patients with immune-mediated diseases."1
References
1. RINVOQ® (upadacitinib) Receives U.S. FDA Approval for Giant Cell Arteritis (GCA). News release. AbbVie. April 29, 2025. Accessed April 30, 2025. https://news.abbvie.com/2025-04-29-RINVOQ-R-upadacitinib-Receives-U-S-FDA-Approval-for-Giant-Cell-Arteritis-GCA
2. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Updated March 27, 2025. Accessed April 30, 2025. https://clinicaltrials.gov/study/NCT03725202
3. Blockmans D., et al. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. N Engl J Med 2025. DOI: 10.1056/NEJMoa2413449.
4. Rinvoq prescribing information. North Chicago, IL: AbbVie Inc; 2019. www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf. Updated August 2019. Accessed April 30, 2025.
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