Real-world Experience of Upadacitinib Reinduction and High-dose Maintenance Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Upadacitinib (UPA) is approved for the treatment of moderately to severely active Crohn's disease (CD) or ulcerative colitis (UC). Responders to UPA 45 mg daily (QD) may lose response (LOR) after transition to lower maintenance doses. We describe our real-world experience of LOR, reinduction, and subsequent maintenance with UPA 45 mg QD.

METHODS

This is a prospective cohort study of patients with inflammatory bowel disease (IBD) treated with UPA between April 2022 and November 2023. Included patients responded to UPA induction, had LOR after dose reduction, and subsequently received reinduction therapy with 45 mg QD. Clinical, biochemical, radiologic, and endoscopic data were collected; comparative statistics and Kaplan-Meier survival were calculated.

RESULTS

A total of 181 patients (79 CD, 83 UC, 6 IBD-Unclassified, 13 ileal pouch anal-anastomosis) responded to UPA 45 mg QD induction and were switched to a lower maintenance dose (30 mg QD, n = 180; 15 mg QD, n = 1), 46 (16 CD, 23 UC, 1 IBD- Unclassified, 6 ileal pouch anal-anastomosis) met the above criteria. They were followed for a median duration 93 weeks (interquartile range [IQR], 62-119 weeks). Relapse occurred at a median of 21 weeks (IQR, 8-46 weeks) after dose reduction. Dose escalation to 45 mg QD for a median of 13 weeks (IQR, 8-36 weeks) recaptured clinical response in 80.4%. Among patients who recaptured response, 19 again reduced to 30 mg or 15 mg. Over a median of 40 weeks (IQR, 22-59 weeks), 93.8% of patients on 45 mg QD maintained remission vs 21.1% who again dropped to 30 mg QD (P < .001). Disease extent and duration did not significantly predict response recapture. Acne/rosacea was the most common adverse event (39%); there were no serious adverse events.

CONCLUSIONS

Most patients with IBD who lose response to UPA when dose reduced in maintenance can be recaptured with 45 mg QD. Among these, continuing 45 mg QD for maintenance is effective, and appears safe.