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A regimen of Rinvoq (upadacitinib) with a 26-week glucocorticoid taper showed superior efficacy in producing sustained remission and in lowering disease flares compared to placebo with a 52-week glucocorticoid taper in patients with giant-cell arteritis, according to results from the Phase III SELECT-GCA trial (NCT03725202) published by The New England Journal of Medicine.1,2 Currently, the only FDA-approved medication indicated for giant-cell arteritis is the interleukin (IL)-6 receptor inhibitor Actemra (tocilizumab). Glucocorticoids are the primary treatment option for the disease, but carry an elevated risk of toxic adverse effects (AEs).
“Approximately 50 to 80% of patients with giant-cell arteritis have a disease relapse when glucocorticoids are tapered. Thus, there is an unmet need for effective, glucocorticoid-sparing treatments for this disease,” the study authors wrote. “[IL]-6 and interferon-γ play major roles in the pathogenesis of giant-cell arteritis and signal through the JAK-STAT (Janus kinase–signal transducer and activator of transcription) pathway. Upadacitinib, an oral and selective Janus kinase (JAK)-1 inhibitor, has the potential to block multiple pathogenic pathways in giant-cell arteritis and received approval for the treatment of several immune-mediated inflammatory diseases.”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.3 The drug is currently 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
Investigators randomly assigned 428 patients with new-onset or relapsing giant-cell arteritis in a 2:1:1 ratio to receive oral upadacitinib 15 mg (n = 209) or 7.5 mg (n = 107) once daily combined with a 26-week glucocorticoid taper, or placebo (n = 112) plus a 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 giant-cell arteritis 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, as well as polymyalgia rheumatica, which has been linked to giant-cell arteritis with many patients experiencing overlapping symptoms, according to the trial 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.
“Giant-cell arteritis disproportionately affects older adults who have coexisting medical conditions (e.g., hypertension, cardiovascular disease, venous thromboembolism, and diabetes) and who are at high risk for glucocorticoid-related adverse events,” the study authors wrote. “Upadacitinib, an oral, targeted therapy, would allow for more-rapid glucocorticoid tapering and less cumulative exposure than treatment with glucocorticoids alone. Oral therapies are generally preferred by most patients over injectable options, particularly by patients with barriers to injections such as older adults with reduced dexterity or impaired vision.”1
References
1. Blockmans D., et al. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. N Engl J Med 2025. DOI: 10.1056/NEJMoa2413449.
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 23, 2025. https://clinicaltrials.gov/study/NCT03725202
3. Rinvoq prescribing information. North Chicago, IL: AbbVie Inc; 2019. www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf. Updated August 2019. Accessed April 23, 2025.