Giant cell arteritis: Upadacitinib may be an upcoming treatment option

Treatment of giant cell arteritis (GCA) with upadacitinib achieved considerable rates of remission in a phase 3 trial. At a regimen of 15 mg daily, 46.4% of the participants reached sustained remission at 52 weeks compared with 29% of those on placebo in the SELECT-GCA trial.

“Advanced targeted therapies are quite limited for GCA, and steroids remain the primary treatment option. Upadacitinib, an oral and selective JAK inhibitor, is a strong inhibitor of the JAK-dependent cytokines IL-6 and IFN-γ and, hence, can interfere with TH17 and TH1 lymphocytes,” Prof. Daniel Blockmans (University Hospitals Leuven, Belgium) explained [1]. He presented the 1-year results of the multinational, randomised-controlled, phase 3 SELECT-GCA trial (NCT03725202) that assessed upadacitinib for GCA in 2 periods of 52 weeks.

The participants (n=428) had a mean age of around 71 years, were mostly women, and 70% had new-onset GCA. They were randomised to upadacitinib at 15 mg or 7.5 mg or a placebo, with a 52-week tapering of corticosteroids. The primary endpoint was sustained remission with the absence of signs and symptoms from GCA from week 12 through week 52. In addition, “patients also needed to adhere to the protocol-defined corticosteroids taper regimen, which I believe is very important,” Prof. Bimba Hoyer (University of Kiel, Germany) commented in her presentation of congress highlights [2].

Sustained remission from weeks 12 to 52 was attained by significantly more participants in the upadacitinib 15 mg group than on placebo: 46.4% versus 29% (P=0.0019; see Figure) [1]. Furthermore, participants on 15 mg of upadacitinib were significantly less likely to encounter a GCA flare up to 1 year with an HR of 0.57 (95% CI 0.40–0.83), and the group on 7.5 mg showed a trend in a similar direction with an HR of 0.75 (95% CI 0.50–1.14). Significance for the higher doses of upadacitinib was also observed for complete remission and cumulative corticosteroid exposure. The cumulative corticosteroid exposure was 1,615 mg on the higher dose of upadacitinib compared with 2,882 mg on placebo.

Figure: Proportion of participants achieving the primary endpoint of sustained remission from week 12 through week 52 [1]



CI, confidence interval; GCA, giant cell arthritis; GC-t, glucosteroid taper; PBO, placebo; UPA, upadacitinib.

On the study drug, event rates per 100 patient-years for herpes zoster were 7.3% (15 mg) and 4.5% (7.5 mg) compared with 4.2% (placebo). The respective results for non-melanoma skin cancer and venous thromboembolism were 2.8% and 1.1% versus 2.1%, and 5.6% and 4.5% versus 4.2%, respectively. “Overall, upadacitinib 15 mg provided a favourable benefit-risk profile and represents a potential new oral targeted therapy for patients with GCA,” Prof. Blockmans concluded.

1. Blockmans D, et al. Efficacy and safety of upadacitinib in patients with giant cell arteritis (SELECT-GCA): a double-blind, randomised controlled phase 3 trial. LBA0001, EULAR 2024 Congress, 12–15 June, Vienna, Austria.
2. Hoyer BF. Highlights from the Clinical Sessions, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 202429 July 2024