P0561 Sustained Corticosteroid-Sparing Effects of Upadacitinib Maintenance Therapy in Patients With Moderate-to-Severe Crohn’s Disease: 2-Year Results From the U-ENDURE Long-Term Extension Study
Authors: Jairath V , Dubinsky M , Biedermann L , Fujii T , Cunneen C , Dubcenco E , Ford S , Garrison A , Loftus Jr. E V 
Published: January 2025

Background

Long-term use of corticosteroids (CS) is a concern for patients with Crohn’s disease (CD), as prolonged use is associated with increased mortality and adverse outcomes. Upadacitinib (UPA), an oral, selective, reversible Janus kinase inhibitor, is approved for the treatment of moderate-to-severe CD and demonstrated CS-sparing efficacy, with a consistent safety profile through maintenance week (wk) 52.1-4 Here, we evaluated the long-term efficacy of UPA in achieving CS-free clinical and endoscopic outcomes in patients enrolled in the ongoing U-ENDURE long-term extension (LTE) study.

Methods

Patients who completed the U-ENDURE 52-wk maintenance study were eligible for the subsequent LTE study wherein they continued their previously assigned treatment (once daily UPA 15 mg [UPA15] or UPA 30 mg [UPA30]). Efficacy was assessed from LTE wk 0-wk48, among patients with 2 year (yr) (100 wk) of total maintenance therapy, within the overall population and in patients with baseline CS use (induction wk 0). CS-free endpoints (without CS use for ≥90 days before evaluation), included clinical remission (per stool frequency/abdominal pain score [SF/APS] and CD Activity Index [CDAI]), endoscopic response, and endoscopic remission, were evaluated using both as-observed and nonresponder imputation (NRI) methods, with NRI analysis presented in text. Safety was not evaluated here but was reported previously.3

Results

Among patients with 2 yr of total maintenance therapy, 35.7% (87/244) received CS at baseline, with 13.1% (32/244) receiving CS at any time during the LTE study regardless of baseline CS use. Among patients taking baseline CS and those who received CS at any time during the LTE study (n=20), the median (range) time of CS use was 127.5 (2-1589) days. CS-free clinical remission was achieved at LTE wk 0 and wk 48 per SF/APS (overall population: UPA15, 71.7%, 58.9%; UPA30, 81.8%, 57.7%; patients with baseline CS use: UPA15, 71.8%, 53.8%; UPA30, 79.2%, 54.2%, NRI, Fig.1A-B) and CDAI criteria (overall population: UPA15, 74.8%, 60.7%; UPA30, 83.9%, 65.0%; patients with baseline CS use: UPA15, 74.4%, 56.4%; UPA30, 81.3%, 58.3%, NRI, Fig.1C-D). At LTE wk 48, a high fraction of UPA-treated patients achieved CS-free endoscopic response (overall population: UPA15, 48.6%; UPA30, 55.5%; patients with baseline CS use: UPA15, 38.5%; UPA30, 60.4%, NRI) and CS-free endoscopic remission (overall population: UPA15, 33.6%; UPA30, 46.0%; patients with baseline CS use: UPA15, 28.2%; UPA30, 54.2%, NRI, Fig.2).

Conclusion

Patients with moderate-to-severe CD who received long-term UPA maintenance treatment sustained high rates of CS-free clinical and endoscopic outcomes, suggesting that UPA may serve as an effective long-term CS-sparing therapy.

References

1.RINVOQ [package insert], extended-release tablets, FDA Prescribing Information. AbbVie Inc; 2022. Accessed 1 June 2022.2.

2.RINVOQ [package insert], prolonged-release tablets. EMA Summary of Product Characteristics. AbbVie; 2022. Accessed 1 June 2022.

3.Loftus EV and Panes J et al. N Engl J Med 2023;388:1966-1980. J

4.M C Dubinsky, et al. JCC, 17; (Supp_1); 2023: i104–i106.