More evidence needed on safety, efficacy of adalimumab in pediatric Crohn's

Last Updated: 2016-04-08

By Marilynn Larkin

NEW YORK (Reuters Health) - The evidence base for the safety and efficacy of adalimumab in pediatric Crohn's disease is of "low quality" and needs to be improved, according to Polish researchers.

"Recently published European consensus guidelines recommended both IFX (infliximab) and ADA (adalimumab) for medical management of children with chronically active luminal disease, with active steroid-refractory disease and as primary induction and for maintenance therapy in children with active perianal fistulising disease in combination with appropriate surgical intervention despite prior optimized immunomodulator therapy," they write in the Journal of Crohn's and Colitis, online March 19.

"Nevertheless, despite (an) increase in ADA use in children there is still uncertainty on ADA efficacy and safety in pediatric population," Dr. Piotr Dziechciarz from The Medical University of Warsaw and colleagues note.

The team searched MEDLINE, EMBASE, the Cochrane Library and abstracts from the main gastroenterologic meetings in the last five years up to July 2015, looking for randomized controlled trials and observational studies on the efficacy and safety of adalimumab for Crohn's treatment in children and adolescents.

Fourteen studies - one randomized controlled trial and 13 case series - which together included 664 patients ages 1.9 to 21 years were included in their analysis. The studies differed with respect to patient characteristics (e.g., percentage of infliximab-naïve patients, disease duration, site of the disease), adalimumab doses, treatment duration and follow-up period.

The researchers found pooled remission rates of 30% (93 of 309 patients) at four weeks, 54% (79 of 145) at three months, 45% (18 of 40) at four months, 42% (146 of 345) at six months, 57% (20 of 35) at eight months and 44% (169 of 383) at 12 months.

Six percent (of 207 patients) were classified as primary nonresponders; 12% (of 599 patients) reported severe adverse events, including two deaths and one medulloblastoma. The withdrawal rate due to adverse events reported in one study was 35% (64 of 182 patients).

When comparing their results to other studies, the authors noted, "In the recently published large registry data set of pediatric Crohn's disease patients treated with anti-tumor necrosis factor alpha, the remission rates at the 26th and 52th week of therapy were respectively 54 % . . . and 66 % . . . which were higher (than) the results of the current study. However these results apply to patients naïve to biologic therapy, contrary to children included in this systematic review which consisted mainly (about 75%) of subjects previously treated with IFX."

They added, "The pooled remission rates in our study are comparable to the results of (a) recently published systematic review of placebo-controlled RCT conducted in adults."

The authors conclude that "according to low quality evidence, based mainly on case series, approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile. There is still a need for high-quality evidence on effectiveness and safety of adalimumab for pediatric Crohn's disease."

Dr. Marla Dubinsky, chief of pediatric gastroenterology and hepatology at The Mount Sinai Hospital in New York City, told Reuters Health that "adalimumab was approved for adults in 2007 and we on the pediatric side used it off-label all the time, since it takes seven to eight years before an agent approved for adults gets to market for kids."

This was also the case for infliximab, which Dr. Dubinsky and colleagues used off-label in children from 1998 to 2006, when it received a pediatric indication.

"This systematic review is based on a lot of case reports because adalimumab has only been approved for use in children since 2014 - so most of its use has been off label," she explained.

"With adalimumab, we get a good outcome, and its safety profile is in line with other therapies in this class for children and adults. We use it just as we do in adults and we have 50% remission," Dr. Dubinsky said. "That's the best we get for any drug in IBD."

The authors did not respond to requests for a comment.

SOURCE: http://bit.ly/1SjoWds

J Crohns Colitis 2016.