In this image, the dilated branches of the temporal artery of a patient with giant cell arteritis are seen. (Click to enlarge.)
Many patients with giant cell arteritis (GCA) who received upadacitinib (Rinvoq) plus a glucocorticoid taper regimen achieved sustained remission, according to a recently published study.1
Upadacitinib could be a long-term therapy that is safer than prednisone, commonly prescribed for GCA, results of the international SELECT-GCA study suggest. It found that 46.4% of patients on 15 mg of upadacitinib daily achieved remission without any rescue glucocorticoids during weeks 12–52 in the 52-week study, compared with 29.0% of 112 patients assigned to a placebo group with an extended glucocorticoid tapering schedule.
GCA, a vascular inflammatory disease, affects primarily large and medium-sized arteries, especially branches of the aorta that supply blood to the head, neck and upper limbs. Symptoms include headaches, scalp, temple or jaw pain, vision impairment and problems related to lack of blood flow. GCA mostly affects adults aged 50 and older, with a global prevalence of 51 cases per 100,000 in this group. The disease is more common in women and in northern European countries and U.S. regions with large populations with northern European ancestry.
Upadacitinib, an oral biologic drug, is currently used to treat various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, Crohn’s disease and juvenile arthritis. The drug reduces inflammation by blocking Janus kinases (JAKs), enzymes involved in the inflammatory response. In April, the European Commission (EC) and the U.S. Food & Drug Administration both approved upadacitinib to treat GCA.
The most common drug used to treat GCA is prednisone, a glucocorticoid associated with many adverse events, especially among older patients with coexisting medical conditions.
Treatment for GCA is usually 12–18 months of glucocorticoids. The present study shows that upadacitinib combined with only six months of prednisone is superior to 12 months of prednisone alone, said first author Daniel Blockmans, MD, PhD, a general internist and professor of medicine at Belgium’s Leuven University. “If a patient does not do well on steroids, if he relapses often or if the patient [can’t tolerate] steroids because of the side effects, now there is another oral drug,” he notes.
In contrast, the only other drug approved for the treatment of patients with GCA, tocilizumab (Actemra), must be injected. Most elderly people prefer pills to injections, Dr. Blockmans says. Tocilizumab reduces inflammation by blocking the interleukin 6 (IL-6) receptor.
The Study
An international team of researchers randomly assigned 428 patients with new-onset or relapsing GCA to three groups and followed them for 52 weeks. Along with tapered glucocorticoids for 26 weeks, 209 patients received 15 mg/day of upadacitinib and 107 received 7.5 mg/day of upadacitinib. In the third group, 112 patients received a placebo on a 52-week glucocorticoid tapering schedule.
The study’s primary end point was sustained remission at week 52, defined by the absence of signs or symptoms of GCA from week 12 through week 52 and adherence to the protocol-specified glucocorticoid taper. Secondary end points included a stricter complete remission standard, meaning sustained remission plus normalization of the erythrocyte sedimentation rate and C-reactive protein levels from week 12 through week 52.
For complete remission, the 15 mg dose was superior to placebo. Proportions of patients achieving complete remission were 37.1% in the 15 mg/day group, 26.2% in the 7.5 mg/day group and 16.1% in the placebo group.
The 15 mg dose was also superior to placebo for disease flares. Just over one-third (34.3%) of patients receiving 15 mg had at least one disease flare, vs. 55.6% of patients who received the placebo. The median total cumulative exposure to glucocorticoids over the course of 52 weeks was 1,615 mg for the patients receiving 15 mg/day, vs. 2,882 mg for the patients receiving the placebo.
Because upadacitinib at a dose of 7.5 mg was not superior to placebo for sustained remission at week 52, researchers did not examine secondary end points for this dose.
The study revealed no new upadacitinib safety risks, Dr. Blockmans notes. Safety outcomes during the 52-week treatment period were similar for the upadacitinib and placebo groups. Although previous studies have shown cardiovascular risk as a potential concern with a JAK inhibitor,2 no major adverse cardiovascular events occurred in the upadacitinib groups.
Serious infections were more common among the placebo group, affecting 10.7% of these patients, vs. 5.7% of the patients receiving 15 mg/day. Given the patients were predominantly elderly, Dr. Blockmans was surprised that no patients in either upadacitinib arm suffered major cardiac events. Meanwhile, 1.8% of patients on placebo did.
Overall, observed adverse events occurred in 95.7% of the patients receiving 15 mg/day, compared with 93.8% in the placebo group. Of these, 22.5% of patients receiving 15 mg/day suffered serious events, compared with 21.4% in the placebo group. In the 15 mg group, 14.8% of patients discontinued the drug due to adverse events, vs. 19.6% in the placebo group.
Trial limitations included a higher-than-expected percentage of patients who discontinued both 15 mg upadacitinib and placebo, 26% and 37%, respectively. Researchers point to timing of the trial during the COVID-19 pandemic. Also, the researchers did not evaluate the efficacy of upadacitinib in patients for whom IL-6 inhibitors had also been ineffective.
The study had two phases, but the paper discusses only data from the first. Dr. Blockmans expects analysis of an extension phase involving 20 patients that will show whether these patients retained their remission and provide further safety data. The paper calls for more, longer-term safety assessments of upadacitinib.
On the Horizon
These first phase results, as well as the EC and FDA approvals are exciting because some rheumatologists and patients now have more treatment options. “No one drug helps all patients,” Dr. Blockmans says.
Investigators are searching for other options. According to Dr. Blockmans, a phase 3 trial is testing secukinumab, a monoclonal antibody or lab-made protein that blocks the cytokine IL-17, a signaling protein, to reduce inflammation.
Other drugs have not advanced to phase 3 trials, Dr. Blockmans notes. He was part of a team that got promising results for mavrilimumab, a monoclonal antibody that targets and inhibits granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) in a phase 2, double-blind, placebo-controlled trial, but the trial sponsor declined to pursue further investigation.3 A study of guselkumab, a monoclonal antibody that selectively targets the p19 subunit of IL-23, was terminated early, he adds.
But upadacitinib is a good new option. “If steroids don’t work, if tocilizumab doesn’t work or if there is a contraindication for it, you have upadacitinib,” Dr. Blockmans says.
He notes that contraindications for tocilizumab include diverticulitis, which is common in elderly patients.
Deborah Levenson is a writer and editor based in College Park, Md.
References
- Blockmans D, Penn SK, Setty AR et al. A phase 3 trial of upadacitinib for giant-cell arteritis. N Engl J Med. 2025 May 29;392(20):2013–2024.
- Goldman A, Galper BL, Druyan A, et al. Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of post-marketing spontaneous safety reports. Semin Arthritis Rheum. 2024 Aug;67:152461.
- Cid MC, Unizony SH, Blockmans D, et al. Efficacy and safety of mavrilimumab in giant cell arteritis: A phase 2, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 May;81(5):653–661.
