Tofacitinib & ASUC

Tofacitinib & ASUC

September 30, 2024

Issue 19

Clinical Question

Should tofacitinib be used in acute severe ulcerative colitis?

Editor’s Bottom Line

These results provide insight into the potential role of JAK inhibitors in managing acute severe ulcerative colitis. More data are needed to clarify the risk-benefit of using tofacitinib doses that are higher than those currently approved.

Reference

Singh A, Goyal MK, Midha V, et al. Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial. Am J Gastroenterol. 2024;119(7):1365-1372. https://journals.lww.com/ajg/abstract/2024.aspx

Synopsis

To determine whether adding tofacitinib to corticosteroids reduces the likelihood of refractory acute severe ulcerative colitis (ASUC), researchers at a tertiary center in Punjab, India, enrolled 104 consecutive adult inpatients with ASUC to take part in a double-blind trial. They randomized 53 patients to receive tofacitinib 10 mg thrice daily with 100 mg intravenous hydrocortisone every six hours and 51 patients to receive the same corticosteroid regimen with a thrice-daily oral placebo, both for seven days.

The patients, who were enrolled in 2021 and 2022, were a median 37.5 years of age. Roughly 57% of patients were male and the median disease duration was two years. Disease characteristics were similar in both arms of the study.

Response to treatment was defined as a decline of more than three points on the Lichtiger Colitis Activity Index and an absolute score below 10 on the Index for two consecutive days, without the need for rescue therapy by day 7 of treatment.

In an intent-to-treat analysis, 83% of those receiving tofacitinib experienced treatment response, compared to 59% of those who received placebo (Odds Ratio [OR]: 3.42; 95% Confidence Interval [CI], 1.37–8.48; p=0.007).

There was a 73% lower likelihood of requiring rescue therapy by day 7 among the tofacitinib recipients than among placebo patients (OR: 0.27; 95% CI, 0.09–0.78; p=0.01). Rescue medical therapy during this period included infliximab (n=5 and 11 in tofacitinib and placebo groups, respectively). One and five patients in the tofacitinib and placebo groups, respectively, underwent colectomy within seven days.

After one week, treatment was unblinded and rates of both medical and surgical rescue therapy remained lower in the patients receiving ongoing tofacitinib up to 90 days of follow-up. Specifically, there was a 0.13 and 0.38 cumulative probability of needing rescue therapy among tofacitinib and placebo recipients, respectively, by 90 days (log-rank p=0.003).

Measures of inflammation and lengths of hospital stay were not statistically different between the groups at day 7.

Roughly 24% of patients in the tofacitinib arm and 14% in the placebo group experienced adverse effects, most of which were mild. One patient receiving tofacitinib developed hemorrhagic venous infarct in the left temporal lobe and dural venous sinus thrombosis.

Five patients died during the 90-day study period. All of these patients were refractory to corticosteroids, were more likely to be malnourished, and several had more severe endoscopic disease. In several cases, patients did not consent to rescue medical or surgical therapy and subsequently died.

Details

Study Design: Double-blind, placebo-controlled
Funding: The Research and Development Center, Dayanand Medical College and Hospital, Ludhiana, India.
Allocation: Randomized
Setting: Single-center
Level of Evidence: 1b