DAY 1 - Extended Induction Treatment with Upadacitinib Improves Outlook for People with Refractory Inflammatory Bowel Disease

Prolonging the upadacitinib induction period or re-escalating the dose may effectively control disease in people with inflammatory bowel disease (IBD) after initial treatment failure, according to a dual-center retrospective analysis featured at the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.

Upadacitinib, an oral Janus kinase (JAK) inhibitor, has shown efficacy in inducing and maintaining remission in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Standard upadacitinib induction therapy consists of 45 mg once daily for 12 weeks in patients with CD and for 8 weeks in those with UC, followed by maintenance dosing with 15 mg or 30 mg, based on disease severity. Extended induction or re-escalation to the induction-period dosing are considered when patients with severe or refractory disease achieve only partial response after induction therapy.

A retrospective analysis, which originated at the New York University Langone Health Center, was designed to look at the efficacy and outcomes of prolonged induction and re-escalation of upadacitinib to induction dosing. The study was then expanded to include patients from the Center for Inflammatory Bowel and Colorectal Diseases at the University of Maryland School of Medicine in Baltimore. Of nearly 600 patients with IBD who had prescriptions for upadacitinib, twenty-nine individuals who were monitored for up to 12 months after the change in therapy were included in the final analysis. The participants had a median disease duration of 8 years and had been exposed to three advanced therapies, on average. A majority of the patients had the UC subtype (19). The records showed that 10 patients (34.5%) needed a prolonged induction period while more than 60% of the participants required dose re-escalation to 45 mg at an average of 6.3 months after induction. Of the ten participants (34.5%) who met the criteria for upadacitinib failure at least one month after prolonged induction or re-escalation, two discontinued upadacitinib and began a new therapy, five required surgical intervention, two others were prescribed a subsequent biologic or small molecule therapy in combination with upadacitinib, and one required new systemic corticosteroid therapy. However, not all patients who required prolonged induction therapy had treatment failure, the authors explained. Upadacitinib was well tolerated overall, with only one patient experiencing treatment-related acne.

“Over two-thirds of patients who received prolonged upadacitinib induction or dose re-escalation persisted on therapy after at least one month without requiring surgery, steroids, or additional biologic or small molecule inhibitors during follow-up,” said lead author Ellen Axenfeld, MD, a fellow in NYU Langone’s Division of Gastroenterology and Hepatology. “In a very medically refractory IBD population, prolonged upadacitinib induction or dose re-escalation may improve the outcome of individual patients.”

The authors said they are planning a prospective, long-term study to confirm the initial findings. “I think the practice has changed, especially at our centers,” Axenfeld said. “People are adopting this [practice] a lot more. This [study] stopped about 6 months ago. Even in that short amount of time, I see [practitioners] doing this a lot more, so hopefully we will have a much larger [group] next time we publish.”