Upadacitinib Demonstrates Long-Term Efficacy in Crohn’s Disease With Acceptable Safety Profile

A long-term open-label extension (OLE) of the CELEST phase 2 trial has shown sustained clinical benefit of upadacitinib in patients with Crohn’s disease, with clinical remission and endoscopic improvements maintained through 30 and 24 months, respectively, according to a report published in Clinical Gastroenterology and Hepatology,

The results also reinforce the established safety profile of the drug.

The study enrolled 107 patients who completed the 52-week CELEST trial. Participants who had received lower doses in the original trial were transitioned to extended-release upadacitinib 15 mg once daily. Those who had received higher doses as rescue therapy were assigned to 30 mg once daily. Patients in the 15 mg group who lost response were eligible for dose escalation to 30 mg.

Clinical remission rates remained stable across groups through month 30. At the end of the follow-up period, remission was observed in 61% of patients on 15 mg, 54% on 30 mg, and 55% in the dose-escalated group. According to the authors, “The proportion of patients with clinical remission...was maintained between week 0 and month 30 in all groups.”

Endoscopic response was similarly maintained through month 24, with 68% of patients on 15 mg and 67% on 30 mg showing improvement. However, response in the dose-escalated group was lower at 40%.

The safety profile aligned with previous studies. The 30 mg group experienced higher rates of adverse events, serious infections, and herpes zoster compared with the 15 mg group. 

The findings suggest upadacitinib provides durable benefit in Crohn’s disease with an acceptable safety profile over long-term use. “Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed,” the investigators concluded.

These results support the continued development and clinical use of upadacitinib as a treatment strategy for patients with moderate-to-severe Crohn’s disease.

Reference
D'Haens G, Panés J, Louis E, et al. Upadacitinib was efficacious and well-tolerated over 30 months in patients with crohn's disease in the celest extension study. Clin Gastroenterol Hepatol. 2022;20(10):2337-2346.e3. doi:10.1016/j.cgh.2021.12.030