FDA Approves Upadacitinib for Adult Patients With Giant Cell Arteritis

Author(s):

Gillian McGovern, Associate Editor

Key Takeaways

Upadacitinib, a JAK inhibitor, is approved for GCA, showing efficacy in multiple inflammatory conditions and undergoing trials for additional indications.
The SELECT-GCA trial demonstrated the 15 mg dose's superiority over placebo in achieving sustained remission with a corticosteroid taper regimen.
GCA, an autoimmune disease affecting arteries, can lead to severe outcomes if untreated, with white women over 50 at highest risk.
Safety profiles of upadacitinib were consistent with previous findings, with no major cardiovascular events observed during the trial.

A 15-mg dose with a corticosteroid taper regimen was superior to placebo in sustained remission from week 12 to 52.

The FDA approved upadacitinib (Rinvoq; Abbvie) for the treatment of adults with giant cell arteritis (GCA). This approval follows clinical findings from the phase 3 SELECT-GCA trial (NCT03725202) as well as the European Commission recently granting marketing authorization of upadacitinib for the same indication.^1,2

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About the Trial

Trial Name: A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA)

ClinicalTrials.gov ID: NCT03725202

Sponsor: AbbVie

Completion Date: February 24, 2025

Upadacitinib is a janus kinase inhibitor (JAK) that works inside a patient’s cells to block certain signals that are believed to be the cause of inflammation. It is a once-daily pill and has demonstrated its ability to help alleviate symptoms in 8 conditions, including the following: moderate to severe rheumatoid arthritis, active psoriatic arthritis (PsA), active ankylosing spondylitis, active nonradiographic axial spondyloarthritis, moderate to severe ulcerative colitis, and moderate to severe Crohn disease in adults; active polyarticular juvenile idiopathic arthritis in children 2 years of age and older as well as PsA in children aged 2 to less than 18 years; and moderate to severe atopic dermatitis in both adults and children aged 12 years and older.³ Currently, the JAK inhibitor is undergoing evaluation in phase 3 clinical trials for alopecia areata, hidradenitis suppurative, Takayasu arteritis, systemic lupus erythematosus, and vitiligo.¹

GCA is an autoimmune disease that causes inflammation of the temporal and other cranial arteries, the aorta, and other large and medium arteries. If not treated, GCA can lead to debilitating symptoms as well as potentially severe outcomes (eg, blindness, aortic aneurysm, or stroke). White women over the age of 50 years (more commonly at 70–80 years) have the highest risk of developing GCA, with research suggesting that men are more likely to have ocular-related manifestations with their disease.^1,3

SELECT-GCA is a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial to assess the safety and efficacy of upadacitinib (7.5 or 15 mg) in patients with GCA. The trial consisted of 2 periods, including an efficacy period as well as a safety and efficacy period. The efficacy period evaluated the efficacy of upadacitinib (7.5 mg dose: n = 107; 15 mg dose: n = 209) compared with placebo (n = 112). Alongside their treatment, patients in the upadacitinib group received a 26-week corticosteroid taper regimen, whereas the placebo group received a 52-week regimen. The second period evaluates the safety and efficacy of continuing compared with withdrawing upadacitinib in maintaining remission in patients who achieved sustained remission during period 1 (primary end point).^1,2,4

The findings demonstrated that 15 mg of upadacitinib with a corticosteroid taper regimen showed superiority (46.4% [95% CI 39.6%–53.2%]) over placebo (29.0% [95% CI 20.6.%–37.5%]) in sustained response (P = .002). Additionally, the 15-mg dose was superior to placebo in the analysis of hierarchically prespecified and multiplicity-controlled key secondary end points, which were sustained complete remission, time to a disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes.^1,4

"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," Roopal Thakkar, MD, executive vice president, research and development, and chief scientific officer, AbbVie, said in a news release. "With this new indication for [upadacitinib], we are underscoring AbbVie's commitment to exploring how we can identify and address unmet needs for patients with immune-mediated diseases."¹

Interestingly, a 7.5-mg dose of upadacitinib (41.1% [95% CI, 31.8 to 50.4]) was not superior to placebo. Safety outcomes during the treatment period of 52 weeks were observed to be similar in the upadacitinib and placebo groups. Although cardiovascular risk is a potential concern with a JAK inhibitor, wrote the authors, no major adverse cardiovascular events were observed in the upadacitinib groups.⁴ Additionally, they noted that the safety profile of upadacitinib was generally consistent with observed profiles in prior FDA-approved indications.¹

"Glucocorticoids remain a mainstay of treatment of GCA but lead to substantial drug-associated toxicities. Additionally, relapse remains common for patients with this disease," trial investigator Peter A. Merkel, MD, MPH, chief of rheumatology at the University of Pennsylvania, Philadelphia, said in the news release. "We now have a new option to treat GCA. The results of this clinical trial show that upadacitinib offers patients the chance to reach sustained remission."¹

REFERENCES

1. AbbVie. RINVOQ® (upadacitinib) Receives U.S. FDA Approval for Giant Cell Arteritis (GCA). News release. April 29, 2025. Accessed April 29, 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). ClincialTrials.gov identifier: NCT03725202. Updated March 27, 2025. Accessed April 29, 2025. https://clinicaltrials.gov/study/NCT03725202

3. RINVOQ® (upadacitinib). About RINVOQ. Accessed April 29, 2025. https://www.rinvoq.com/

4. Blockmans D, Penn SK, Setty AR, et al. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. New Engl J Med. Published April 2, 2025. doi:10.1056/NEJMoa2413449