Management of acute severe ulcerative colitis (ASUC) remains difficult with questions around the optimal timing and dose of infliximab as a rescue therapy in order to prevent colectomy, an Australian gastroenterologist says.

Recent British Society of Gastroenterology guidelines (2019) suggest patients treated with infliximab for ASUC who have not responded sufficiently to a 5mg/kg dose 3–5 days after first infusion should be treated with an accelerated dose (AD) induction regimen.

The stipulation however is that AD should only be given after colorectal surgical review confirms emergency colectomy is not required.

According to an Editorial in the latest issue of Digestive Diseases and Sciences, co-authored by Dr David Gibson from the Alfred Hospital, Melbourne, accelerated dose (AD) induction remains in widespread use for steroid-refractory ASUC.

And it is worth getting the process optimised.

“Since no new medical therapies have become available for ASUC in the last decade that in turn restricts the available therapeutic options, it is paramount to further refine IFX dosing and the understanding of drug pharmacokinetics in this difficult-to-treat population.”

“Perhaps with the addition of point-of-care testing using a minimal trough cutoff prior to next scheduled dose will help improve outcomes for our patients, although the desirable drug level in this cohort is unknown,” they suggested.

The authors were commenting on a retrospective US study which compared outcomes following single dose infliximab at 5mg/kg or 10mg/kg versus AD of two doses three days apart in patients who only had a partial response to the initial dose.

The study found the colectomy rates were statistically similar in the two patient groups – 24.2% with a single dose and 30.3% with the AD protocol (p=0.58).

There was no difference in the use of 10 mg/kg as the initial dose between accelerated induction and single-dose rescue induction groups (66.7% vs 63.6%, p=0.80).

Perhaps not surprisingly, the study reported that all patients offered a second dose of infliximab preferred that option to colectomy.

“Among patients who ultimately underwent colectomy, we did not find an increased risk of complications or readmission, but complication and readmission rates for these patients were high,” the study said.

The Editorial added that the entire IBD community was looking forward to results of PREDICT-UC – “the only randomised controlled trial of infliximab dosing in ASUC.”

“Yet, it is likely that even with these results, some unanswered questions will remain,” it said.