New Data Further Support Safety of Upadacitinib With 26-Week GC Taper for Giant Cell Arteritis

New research examining the rates of serious infections in people with giant cell arteritis (GCA) supports the use of upadacitinib 15 mg with a shorter glucocorticoid (GC) tapering than placebo with a longer taper.1

These findings were presented at the European Alliance of Associations for Rheumatology (EULAR) Congress 2025 in Barcelona, Spain, taking place June 11-14, 2025.

“In the SELECT-GCA phase 3 trial, upadacitinib once daily in combination with a protocolized 26-week GC taper demonstrated a favorable benefit-risk profile compared with placebo with a protocolized 52-week GC taper, providing an alternative option to reduce GC dependency while maintaining disease control in patients with GCA5,” lead investigator Frank Buttgereit, MD, Professor of Rheumatology and Deputy Head of the Department of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, and colleagues wrote in their presentation.1 “To assess the occurrence of adverse events of serious infection, herpes zoster, and opportunistic infection during concomitant treatment with GCs and after GC tapering in patients with GCA receiving upadacitinib or placebo.”

In the SELECT-GCA trial, participants underwent an open-label GC taper regimen until the dose reached 20 mg per day, after which it was blinded. The glucocorticoid taper regimens were tailored to each patient on the basis of the starting dose, with the patients in the upadacitinib groups discontinuing by week 26 and those in the placebo group discontinuing by week 52. Baseline characteristics, including GC doses, were similar across treatment groups, and most patients received a glucocorticoid dose between 20 to 40 mg at baseline. Based off safety and efficacy data from SELECT-GCA, upadacitinib 15 mg once daily was approved for the treatment of adults with GCA under the name Rinvoq in April 2025.2

The investigators found that the rates of serious infections were numerically lower with both 15- (7.9 events/100 patient-years [E/100 PY]; 95% CI, 4.3-13.2) and 7.5-mg (7.9 E/100 PY; 95% CI, 3.2-16.3) doses of upadacitinib than with placebo (12.7 E/100 PY; 95% CI, 6.6-22.2) through week 52. In contrast, rates of herpes zoster, a known risk for JAK inhibitors including upadacitinib were higher with UPADACITINIB15 mg (7.3 E/100 PY; 95% CI, 3.9-12.5) but not upadacitinib 7.5 mg (4.5 E/100 PY; 95% CI, 1.2-11.6) compared with placebo (4.2 E/100 PY; 95% CI, 1.2-10.9).1

The rates of opportunistic infections were low in all groups, and although numerically higher in the upadacitinib 15 mg group compared to placebo, these were based on a small number of events, and no opportunistic infections were reported in the upadacitinib 7.5 mg group. One case of opportunistic infection, that of Pneumocystis jiroveci pneumonia, was considered serious and led to discontinuation of upadacitinib in the 15 mg group. All other opportunistic infections were mild or moderate in severity and none led to discontinuation.

Notably, serious infection rates were numerically lower in the post-taper period with upadacitinib 7.5 mg (3.4 E/100 PY; 95% CI, 0.7-9.9) or 15 mg (3.9 E/100 PY; 95% CI, 1.6-8.1) relative to placebo (8.5 E/100 PY; 95% CI, 3.7-16.7) and Herpes zoster rates were similar with upadacitinib15 mg relative to placebo during and after the prespecified GC taper. Of the 4 opportunistic infections with upadacitinib 15 mg, 3 occurred during the prespecified GC taper and 1 after in a patient receiving GC escape therapy. The investigators also found that baseline GC dose did not have a clear impact on the occurrence of serious infections.1

“The decrease in serious infection rates during the GC-free phase suggests concomitant use of GCs may contribute to the risk of serious infections,” Buttgereit and colleagues wrote.1 “Overall, these results, together with the superior efficacy of upadacitinib15 mg with a 26-week GC taper compared to placebo with a 52-week GC taper, support the potential benefits of a shorter GC taper period.”

During EULAR, AbbVie also presented biomarker data from SELECT-GCA. Among the key findings were that upadacitinib inhibits key immune pathways driving pathogenesis of GCA, including IL-6 and IFN-related proteins; UPA reduced IL-6 and IL-18, the monocyte attractant CCL7, and the IFN-associated chemokines CXCL9, CXCL10, and CXCL11, compared to placebo, indicating broad suppression of inflammatory mediators; and IL-6 levels distinctly differentiated responders from non-responders, which may offer insights into the mechanisms of response to treatment.3

REFERENCES

1. Buttgereit F, Winthrop KL, Calabrese LH, et al. Impact of Glucocorticoid Tapering in Giant Cell Arteritis: Analysis From the SELECT-GCA Trial. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0057

2. RINVOQ® (upadacitinib) Receives U.S. FDA Approval for Giant Cell Arteritis (GCA). News release. AbbVie. April 29, 2025. https://news.abbvie.com/2025-04-29-RINVOQ-R-upadacitinib-Receives-U-S-FDA-Approval-for-Giant-Cell-Arteritis-GCA

3. Christ L, Taylor S, Xu Y, et al. Impact of Treatment with Upadacitinib on Biomarkers Identified by Proteomics in Giant Cell Arteritis. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0022