IFX rescue for ASUC

October 28, 2024

Issue 21

Clinical Question

Is there an optimal infliximab rescue regimen for acute severe ulcerative colitis?

Editor’s Bottom Line

While these results do not provide support for routine use of high-dose infliximab as rescue therapy for acute severe ulcerative colitis, patients with low serum albumin and higher inflammatory burden may benefit. More data on such high-risk subgroups are needed.

Reference

Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2024;9(11):981–96. https://www.thelancet.com

Synopsis

To determine the optimal rescue dosing strategy for infliximab (IFX) in steroid-refractory acute severe ulcerative colitis (ASUC), researchers at 13 Australian tertiary hospitals compared intensified and standard-dose IFX rescue strategies in 46 patients randomized to receive 10 mg/kg IFX (intensified) and 92 patients randomized to receive a 5 mg/kg (standard) IFX dose.

Patients were divided roughly evenly by sex, and the duration of disease averaged between 2 and 4.3 years in the groups.

Patients in the intensified IFX group received a second 10 mg/kg dose at Day 7, or earlier if they did not experience a clinical response. Clinical response was defined as a Lichtiger score <10 with a decrease of at least 3 points from baseline and improvement in rectal bleeding as well as no more than four bowel movements daily.

Meanwhile, patients who received the initial 5 mg/kg dose were re-randomized between Days 3 and 7 to receive either standard induction again or accelerated induction. Standard induction included 5 mg/kg IFX doses at weeks 0, 2, and 6, with an extra 5 mg/kg dose between Day 3 and Day 7 if they did not have a clinical response. The accelerated regimen consisted of 5 mg/kg IFX at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between Day 3 and Day 7 in case of no clinical response by Day 7.

Maintenance therapy after three months was chosen based on prior treatment experience and consisted of either thiopurine monotherapy, combination IFX and a thiopurine, or IFX alone.

In intent-to-treat analyses, there were no significant differences in the proportion of patients with a clinical response by Day 7. In the intensified and standard IFX induction rescue therapy groups, 65% and 61% of the two groups, respectively, experienced clinical response within one week. There were also no significant differences in time-to-clinical response or in the change in Lichtiger score from baseline to Day 7. Rates of clinical response by day 7 were numerically, but not statistically, higher in the intensified group among those with baseline albumin less than 25 g/L (64% vs. 45%) and among those with baseline CRP 50 mg/L or higher (60% vs, 42%).

Two patients who received 10 mg/kg IFX underwent colectomy within 7 days of the initial rescue dose, compared with no patients in the 5 mg/kg group (p=not significant). Safety results in the first week were also similar between groups, with three patients each in the standard and intensified groups experiencing a serious adverse event.

Results at 14 days and three months were also not significantly different among those administered the initial higher dose and those given the 5 mg/kg rescue dose and then re-randomized to receive IFX either in an accelerated or a standard fashion.

Specifically, clinical response rates at Day 14 for the intensified, standard or accelerated groups were 74%, 73% and 68%, respectively; clinical remission rates at three months were 50%, 52%, 48%, respectively; steroid-free remission rates at three months were 41%, 42%, 41%, respectively; endoscopic remission rates at three months were 46%, 46%, and 48%, respectively; and colectomy rates at three months were 7%, 19% and 12%, respectively.

There were no significant differences in rates of infectious adverse events possibly related to IFX during the study and there were no deaths.

 

Details

Study Design: Controlled trial
Funding: The NHRMRC, the Gastroenterology Society of Australia Bushell Fellowship, a Gandel Philanthropy Major Grant, an Australian Postgraduate Award, and a Janssen-Cilag grant.
Allocation: Randomized
Setting: Multicenter
Level of Evidence: 1a