Upadacitinib Maintenance Therapy in Crohn's Disease: Final Results From the Randomized Phase 3 U-ENDURE Study

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Crohn's disease is a chronic inflammatory bowel disease.
• Upadacitinib is an oral Janus kinase inhibitor.
• Previous trials (U-EXCEL, U-EXCEED) showed efficacy and safety in Crohn's disease.

Purpose of the Study:

• To evaluate the efficacy and safety of upadacitinib maintenance therapy in a broader Crohn's disease population.
• To present overall results from the U-ENDURE trial (N=673).

Main Methods:

• Randomized controlled trial (U-ENDURE) involving 673 patients.
• Patients who responded to 12-week upadacitinib induction were randomized to upadacitinib 15 mg, 30 mg, or placebo for 52-week maintenance.
• Coprimary endpoints: Crohn's Disease Activity Index (CDAI) clinical remission and endoscopic response at week 52.

Main Results:

• Higher rates of CDAI clinical remission with upadacitinib 15 mg (36.2%) and 30 mg (51.5%) versus placebo (15.2%) at week 52.
• Significantly higher endoscopic response rates for upadacitinib 15 mg (27.3%) and 30 mg (40.7%) compared to placebo (7.2%).
• Numerically lower exposure-adjusted event rates for treatment-emergent adverse events with upadacitinib versus placebo, with increased herpes zoster infections.

Conclusions:

• Upadacitinib demonstrated superior efficacy over placebo for clinical and endoscopic endpoints in Crohn's disease maintenance.
• The safety profile of upadacitinib was consistent with prior studies, showing no new safety signals.
• Upadacitinib is an effective oral treatment option for Crohn's disease.