Prior Relapse Predicts Faster Flare After Stopping Upadacitinib in GCA

Withdrawing upadacitinib 15 mg/day (UPA15) after sustained remission carries meaningfully greater flare risk in patients with relapsing giant cell arteritis (GCA) compared with those with new-onset disease, according to a post hoc analysis of the SELECT-GCA phase 3 extension period presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdom.¹

Anisha Dua, MD, MPH, Professor of Medicine in the Division of Rheumatology and Director of the Northwestern Vasculitis Center at Northwestern University Feinberg School of Medicine, Chicago, presented the findings, and sat down with RheumatologyLive during the meeting to further discuss the importance of the new data.

SELECT-GCA enrolled patients aged ≥50 years with new-onset or relapsing active GCA, randomized in period 1 (weeks 0–52) to UPA15, upadacitinib 7.5 mg/day with a 26-week glucocorticoid (GC) taper, or placebo with a 52-week GC taper.² Patients who achieved remission for ≥24 consecutive weeks by week 52 entered period 2 (weeks 52–104), where UPA-treated patients were re-randomized 2:1 to continue UPA15 or switch to placebo. Of 103 patients entering period 2, 75 (72.8%) had new-onset disease and 28 had relapsing disease — a sample size the authors acknowledge as a limitation of this post hoc analysis. Mean age across subgroups was 70.8 years.¹

Regardless of baseline disease status, continuous UPA15 conferred ≥90% reduction in risk of disease flare versus placebo switch from weeks 52 to 104 in both the new-onset and relapsing subgroups.¹ Among patients who switched to placebo, the divergence by disease status was substantial: 89% of relapsing patients experienced ≥1 disease flare compared with 49% of new-onset patients. Relapsing patients who switched to placebo also had a notably shorter time to first flare. Remission was maintained in only 11% of relapsing placebo-switch patients versus 39% of new-onset placebo-switch patients; complete remission (normalization of ESR and CRP) was maintained in 0% versus 19%, respectively. Cumulative GC exposure from weeks 52 to 104 was markedly higher in the relapsing placebo-switch subgroup versus new-onset (median: 2297 mg vs 110 mg), while continuous UPA15 patients required a median of 0 mg in both subgroups. Among patients who remained on UPA15, >70% maintained remission and ≥59% maintained complete remission in both subgroups through week 104.1 No new safety signals were identified through 2 years.

"I would not stop [upadacitinib] at 1 year, ideally, unless there was a major reason to do so, but at least you can have a better conversation with patients about what their risk might be if they came into treatment initially with new onset or relapsing disease," Dua said. "I would probably be more hesitant to try to stop sooner in those with relapsing disease."

The authors caution that findings from this post hoc analysis should be interpreted in the context of the limited relapsing subgroup size.1

Dua’s disclosures include AbbVie, Amgen, Novartis, Sanofi, GSK, and Astra Zeneca.

References

1. Dua AB, Schmidt W, Dejaco C, et al. Response to upadacitinib in new-onset versus relapsing giant cell arteritis: two-year outcomes from the SELECT-GCA phase 3 trial [abstract OP0117]. Ann Rheum Dis. 2026;85(suppl 1):s99. doi:annrheumdis-2026-eular.B.1131

2. Blockmans D, Penn SK, Setty AR, et al; SELECT-GCA Study Group. A phase 3 trial of upadacitinib for giant-cell arteritis. N Engl J Med. 2025;392(20):2013–2024. doi:10.1056/NEJMoa2413449