Favourable benefit-risk profile of upadacitinib in giant cell arteritis

In the primary analysis of the SELECT-GCA trial, upadacitinib 15 mg was superior to placebo in sustaining remission in patients with giant cell arteritis (GCA). The JAK-STAT inhibitor was combined with a 26-week taper regimen of glucocorticoids, which was also more effective than placebo with a 52-week glucocorticoid taper.

Upadacitinib is an oral inhibitor of the JAK-dependent cytokines IL-6 and IFNγ. Prof. Peter Merkel (University of Pennsylvania, PA, USA) and colleagues assessed its efficacy and safety, in combination with a glucocorticoids taper regimen, for the treatment of GCA in the phase 3 SELECT-GCA trial (NCT03725202) [1]. Prof. Merkel presented results from the first of 2 blinded 52-week study periods. Inclusion criteria were age ≥50 years, new-onset or relapsing GCA, and glucocorticoid use.

The 428 participants had a mean age of 71 years, 27% were men, and 30% had relapsing GCA. They received upadacitinib 7.5 mg (n=107), upadacitinib 15 mg (n=209), or placebo (n=112) once daily. This treatment was combined with a glucocorticoid taper regimen of 26 weeks in the upadacitinib groups and 52 weeks in the placebo group. The primary endpoint was sustained remission, defined as the absence of signs or symptoms of GCA from weeks 12–52 and adherence to the glucocorticoid taper regimen.

A significantly higher rate of participants in the upadacitinib 15 mg group achieved sustained remission versus placebo at week 52: 46.4% and 29.0%, respectively (P=0.0019). With upadacitinib 15 mg, 9 of 11 multiplicity-controlled secondary endpoints were also met. Cumulative median glucocorticoid exposure was significantly lower with upadacitinib 15 mg compared with placebo: 1,615 versus 2,882 mg (P<0.0001). This was unsurprising, according to Prof. Merkel, as the placebo group had a longer tapering period. It still confirms that the protocol was adhered to and that this strategy allows glucocorticoid reduction. There were no new safety signals. Rates of treatment-emergent adverse events, including serious infections and major cardiac events, were similar across all 3 groups. Prof. Merkel added that there were no more cases of venous thromboembolism than with placebo: 5.6 events per 100 person-years in the upadacitinib 15 mg group versus 4.2 with placebo.

1. Merkel P, et al. Efficacy and safety of upadacitinib in patients with giant cell arteritis (SELECT-GCA): A double-blind, randomized controlled phase 3 trial. Abstract 0770, ACR Convergence 2024, 14–19 November, Washington DC, USA.

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Posted on 13 January 202513 January 2025