Upadacitinib Emerges as Rescue Therapy for Severe Ulcerative Colitis | Gastro Today

In a recent multicenter study, investigators reported that upadacitinib could serve as a therapeutic rescue option for patients with acute severe ulcerative colitis (ASUC) after treatment with IV corticosteroids (IV-CS) and infliximab has failed.

Upadacitinib Shows Promise as an Ulcerative Colitis Rescue Therapy

Nalan Gülşen Ünal, MD, PhD, of Ege University in Türkiye, and colleagues conducted the study and published their findings in Inflammatory Bowel Diseases.

The investigators explained that data on use of upadacitinib in the third line as a rescue option for treatment of IV-CS- and infliximab-refractory ASUC are limited.

The investigators recruited 50 patients with ASUC who had been hospitalized and met Truelove and Witts criteria for UC severity. Eligible patients had received upadacitinib in the third line after treatment with IV-CS and infliximab failed.

Study outcomes that were measured over 48 weeks of follow-up included clinical remission; partial Mayo score (pMAYO) of at least 2; continued upadacitinib therapy; clinical response, defined as a reduction of 3 or more points in pMAYO score; and colectomy rates.

Eligible patients were enrolled from 11 medical centers, and 54% of patients were male. Eighty-six percent of the study cohort had been previously treated with infliximab, and more than 50% of the study cohort had been previously treated with two or more biologic therapies.

According to the results, 90% of participants continued treatment with upadacitinib at week 4, with 52% continuing treatment at the 48-week mark. The investigators highlighted reasons for treatment discontinuation, with 42% of patients discontinuing upadacitinib due to primary nonresponse, 46% due to secondary loss of response, and 13% due to other causes.

Upadacitinib-related adverse events were observed in 24% of patients. and most were classified by investigators as not severe. Twenty-two percent of the study cohort required colectomy, with almost half of colectomies performed in week 1.

Reductions in C-reactive protein (CRP) levels and pMayo scores and rectal bleeding and stool frequency occurred by week 1 of upadacitinib treatment and were maintained to the 48-week mark.

Complete response (CR) rates were also reported by investigators. They wrote, “Week 1 CRs were 60%/30% while the week 48 CR rate was 51%.” In addition, although a higher baseline CRP level was found to predict colectomy, no laboratory markers or other factors had an effect on continuation of treatment with upadacitinib.

In reflecting on the findings, the investigators reported that “third-line upadacitinib was associated with a low colectomy rate and sustained response up to 1 year, with an acceptable safety profile.”

They concluded that upadacitinib “may provide sufficient disease control to prevent or delay colectomy, or to serve as a bridge to alternative therapies.”