Tofacitinib improves response, lowers mortality in acute severe ulcerative colitis

In patients with acute severe ulcerative colitis (UC), the addition of tofacitinib to corticosteroids results in better response to treatment, reveals a study. This benefit persists beyond 7 days, as shown by the lower rates of medical or surgical rescue therapy at 90 days.

Additionally, tofacitinib treatment is associated with reduced rates of disease-related mortality.

In this single-centre, double-blind, placebo-controlled trial, researchers randomized adults with acute severe UC (defined by the Truelove Witts severity criteria) to receive either tofacitinib 10 mg thrice daily or matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). All analyses were done in the intention-to-treat population.

Treatment response (defined by a decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7 was the primary endpoint. The secondary outcome was the cumulative probability of requiring infliximab or undergoing colectomy within 90 days after randomization.

Of the 104 eligible patients, 53 were randomized to tofacitinib and 51 to placebo. More patients in the tofacitinib group achieved response to treatment at day 7 than those in the placebo group (83.01 percent [44/53] vs 58.82 percent [30/51]; odds ratio [OR], 3.42, 95 percent confidence interval [CI], 1.37‒8.48; p=0.007). [Am J Gastroenterol 2024;119:1365-1372]

In addition, fewer patients in the tofacitinib arm required the need for rescue therapy by day 7 (OR, 0.27, 95 percent CI, 0.09‒0.78; p=0.01). At day 90, the cumulative probability of need for rescue therapy was 0.13 in tofacitinib-treated patients as opposed to 0.38 in those receiving placebo (log-rank p=0.003).

Adverse events

In terms of safety, treatment-related adverse effects were mild, and only one patient on tofacitinib developed dural venous sinus thrombosis.

“Tofacitinib has been reported to be associated with increased risk of major adverse cardiovascular events in patients with rheumatoid arthritis,” the researchers said. “However, these findings have not been replicated in patients with UC.”

An earlier study reported that the risk of thrombotic events with tofacitinib in UC was similar to that with anti-TNF agents. [Dig Dis Sci 2022;67:5206-5212]

In another study, data from the UC clinical program showed a higher incidence of adverse events, including major adverse cardiovascular events, with increasing age (>65 years), but the sample was small. A recent systematic review also reported one case each of venous thromboembolism and death in patients with acute severe UC. [Inflamm Bowel Dis 2022;29:27-41; J Crohns Colitis 2023;17:1354-1363]

“Similar rates of serious adverse effects were reported in [the current] study,” the researchers said. “One patient developed haemorrhagic venous infarct and dural venous sinus thrombosis,” which could be attributed to tofacitinib.

“Further studies assessing the efficacy of tofacitinib, either as monotherapy or in combination with other therapies, are needed to determine the position of tofacitinib in the therapeutic algorithms of ASUC,” according to the researchers.

“An exploratory signal of increased corticosteroid responsiveness with tofacitinib, in patients with previous exposure to thiopurines or ongoing oral corticosteroids during hospitalization, warrants further evaluation,” they added.