Infliximab induction levels predict IBD treatment failure

Last Updated: 2017-06-07

By Will Boggs MD

NEW YORK (Reuters Health) - Lower infliximab trough levels during induction are associated with an increased risk of treatment failure during maintenance in patients with inflammatory bowel disease (IBD), researchers report.

"These results were a little surprising because of few data before our analyses,” Dr. Claire Liefferinckx from Universite libre de Bruxelles, Brussels, Belgium told Reuters Health. “Most of all, these results are very interesting because it's a new way to better understand the loss of response observed more frequently in the follow-up.”

Infliximab is effective for inducing and maintaining remission in patients with Crohn's disease and ulcerative colitis, but loss of response (LOR) occurs in as many as 30% of patients over 12 months of treatment.

Dr. Liefferinckx and colleagues evaluated the impact of the pharmacokinetics of infliximab at induction (weeks 2 and 6) on treatment failure in their longitudinal study of 269 patients with inflammatory bowel diseases.

They divided patients into 4 groups: “LOR switched” included 28 patients who required switching to another treatment because of loss of response; "LOR optimized" included 60 patients who experienced LOR but responded to infliximab optimization (by shortening the interval or increasing the dose); "long-term responders" included 64 patients who were treated with infliximab without requiring optimization; and “stop group” included 58 patients who stopped treatment because of deep remission. There were a total of 207 patients in the trough level analyses.

Median infliximab trough levels at induction did not differ significantly between the long-term responders (11.89 mcg/mL) and the LOR optimized group (9.85 mcg/mL) but were significantly lower in the LOR switched group (4.4 mcg/mL), according to the May 11 Inflammatory Bowel Diseases online report.

In the LOR switched group, but not in the LOR optimized group or long-term responders, median infliximab trough levels at induction were significantly lower in previously exposed patients than in naïve patients.

The LOR switched group also had lower median infliximab trough levels (1.43 mcg/mL) during maintenance than did the long-term responders (2.15 mcg/mL) and the LOR optimized group (2.59 mcg/mL).

The prevalence of antibodies to infliximab was significantly lower in long-term responders (5.7%) than in the LOR optimized (37.5%) and LOR switched (40%) groups.

“This study suggests that the induction may be a (moment) to discriminate patients who will maintain response or fail to (respond to) infliximab during treatment maintenance, especially in patients with previous exposure to anti-TNFs,” the researchers conclude.

“This study is retrospective,” Dr. Liefferinckx said. “Consequently, some cautions are required. Nevertheless, we are currently managing a prospective study with a design focusing on the induction phase. With confirmation of our results, probably we will use trough level in induction in order to rapidly modify the scheme of treatment if needed.”

“Of course, these conclusions and message need to be reinforced by other studies,” she continued. “More globally, in the current context of economic problems, we think that the pharmacokinetic monitoring of biologics will be an important part in the management of IBD patients both in induction and maintenance.”

SOURCE: http://bit.ly/2r5RhOd

Inflamm Bowel Dis 2017.