Infliximab may effectively treat pediatric Crohn's over the long term

Last Updated: 2017-07-20

By Marilynn Larkin

NEW YORK (Reuters Health) - Infliximab may be an effective long-term treatment for children with Crohn's disease, although optimization will likely be needed, researchers in Canada say.

"Twenty to thirty percent of those who develop inflammatory bowel disease are diagnosed in their childhood or adolescent years. The burden of disease is large, including decreased quality of life, school and work absenteeism, hospitalizations, and surgeries," lead author Dr. Jennifer deBruyn of the University of Calgary told Reuters Health.

"A recent network meta-analysis affirmed infliximab as one of the most effective therapies for induction and maintenance of remission in adults with Crohn's disease," she said by email. "However, only limited studies have evaluated the long-term durability of infliximab for pediatric Crohn's disease in real-world practice."

To investigate, Dr. deBruyn and colleagues analyzed data from 2008 to 2012 on 180 children (54% males) with Crohn's disease who started taking infliximab at a median age of 14. The median time from diagnosis to infliximab start was 1.5 years, and the median follow-up time was seven years.

The most frequent indications for use were chronic active disease (47%), severe exacerbation (14%), extensive disease (15%) and severe perianal disease (14%).

Sixty-six percent of children either continued or started taking an immunomodulator - mainly azathioprine or methotrexate - concomitantly with infliximab.

As reported in the Journal of Pediatric Gastroenterology and Nutrition, online June 28, at last follow-up, 87% were maintained on infliximab.

Optimization was required by 57% of children, mainly due to loss of response: dose escalation, 15.2%; interval shortening, 3.9%; and both, 38.2%. Optimization was associated with age <10 years at diagnosis (odds ratio, 6.5) and non-stricturing, non-penetrating disease behavior (OR, 2.1).

More than 95% of children continued on maintenance infliximab for at least one year and more than 90% continued for at least two years. Discontinuation due to loss of response occurred at a rate of about 3% per year.

Dr. deBruyn said, "Our results support the role of infliximab as a strong therapeutic option in pediatric Crohn's disease and can be used by clinicians . . . to provide guidance on infliximab use and projected outcomes."

Principal author Dr. Hien Huynh of the University of Alberta in Edmonton added in a separate email that "infliximab has become the best drug we have in the treatment of Crohn's, particularly in children if used well, (and) it will likely remain one if our most effective treatments for many years to come."

"A well designed trial is still needed to assess weaning off" in children with moderate-to-severe Crohn's, since the risk of relapse is high after treatment is stopped, he said.

Dr. Keith Benkov of the Icahn School of Medicine at Mount Sinai told Reuters Health that while infliximab is very effective in controlling inflammation and complications associated with Crohn's, "the major problem with its use has been the durability of its effect."

"In this series, the authors demonstrated greater than a 90% sustained rate, which is a little higher than previously reported rates, but still very feasible," he said by email.

One caveat, he added, is that close to two-thirds were also taking an immunomodulator, "which is a little bit higher than usually seen. Immunomodulators have been shown to increase the sustainability of infliximab but also have the potential for increasing side effects."

Dr. Benkov also noted, "I don't get a good feeling for how sick this group of patients are, as patients with mild illness might respond better to infliximab therapy."

"Because it is a retrospective study, there are additional biases," he concluded.

Dr. deBruyn, Dr. Huynh and five coauthors have participated in advisory boards and/or received fees from Janssen Biotech, which markets infliximab as Remicade, and Abbvie, which markets an infliximab biosimilar.

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

J Pediatr Gastroenterol Nutr 2017.