Upadacitinib Shows Rescue Potential for Severe Ulcerative Colitis After Steroid and Infliximab Failure

Fifty people were admitted to hospital with acute severe ulcerative colitis. Intravenous corticosteroids had not brought their disease under control, and neither had infliximab. For these patients, the standard options had run out, and surgery to remove the colon was the next step. A group of researchers has now looked at what happened when they were given a third-line drug, upadacitinib.

The work was led by Nalan Gülşen Ünal, MD, PhD, of Ege University in Türkiye, with colleagues, and appears in Inflammatory Bowel Diseases. The investigators noted at the outset that data on upadacitinib as a third-line rescue for acute severe ulcerative colitis, refractory to both IV steroids and infliximab, are limited. This study was an attempt to add to that thin evidence.

Patients were drawn from 11 medical centers. All had been hospitalized and met the Truelove and Witts criteria for severe disease, and all had received upadacitinib in the third line after the first two treatments failed. Fifty-four percent were male. Eighty-six percent had previously been treated with infliximab, and more than half had previously received two or more biologic therapies, so this was a heavily pretreated group.

The team followed them for 48 weeks. Outcomes included clinical remission, continuation of upadacitinib, clinical response (defined as a drop of 3 or more points in partial Mayo score), and colectomy rates.

At week 4, 90% of participants were still taking upadacitinib. By week 48, 52% remained on it. Among those who stopped, 42% did so because of primary nonresponse, 46% because of secondary loss of response, and 13% for other reasons. Adverse events related to the drug occurred in 24% of patients, and the investigators classified most as not severe.

The human cost of the study is in the surgical numbers. Twenty-two percent of the cohort required colectomy, and almost half of those operations took place in the first week of upadacitinib treatment. That suggests that for some patients the drug did not act quickly enough, or the disease had already advanced too far.

For those who did respond, the improvement was fast. C-reactive protein levels, partial Mayo scores, rectal bleeding and stool frequency all fell by week 1 and the gains held through week 48. The investigators reported complete response rates of 60% and 30% at week 1, and 51% at week 48. A higher baseline CRP predicted colectomy, but no laboratory marker or other factor affected whether patients stayed on upadacitinib.

The authors wrote that third-line upadacitinib was associated with a low colectomy rate and a sustained response up to a year, with an acceptable safety profile. They concluded it may provide enough disease control to prevent or delay colectomy, or to serve as a bridge to other therapies.

The evidence has limits. With 22% of patients still going to surgery and the study lacking a comparison group, larger controlled trials will be needed to establish where upadacitinib belongs in the treatment of severe disease after steroids and infliximab have failed.