Vedolizumab appears effective in kids with refractory IBD

Last Updated: 2017-07-04

By Will Boggs MD

NEW YORK (Reuters Health) - The anti-integrin antibody vedolizumab appears also to be effective in children with refractory inflammatory bowel disease (IBD), according to a retrospective study.

"Vedolizumab is another treatment option that's available for us,” said Dr. Oren Ledder from Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, in Jerusalem, Israel.

“Unfortunately, though, it is far from universally effective, but it did significantly help almost 40% of ulcerative colitis (UC) patients and almost 25% of Crohn’s disease (CD) patients who had failed multiple other treatments,” he told Reuters Health by email.

Vedolizumab is approved for induction and maintenance of remission in both UC and CD and has been used off-label in children with IBD who have exhausted other treatment options. But two case series of vedolizumab treatment, one with 52 children and one with 21 children, yielded inconsistent results, Dr. Ledder and colleagues note in the Journal of Crohn's and Colitis, online June 9.

The team used data from 19 centers in Europe and Israel, including all children who received at least one infusion of vedolizumab, in their retrospective observational study of short- and long-term outcomes of vedolizumab in pediatric IBD.

All children had previously been exposed to anti-TNF drugs, and 63% had moderate or severe disease activity at initiation of vedolizumab treatment.

During follow-up, 14 patients (22%) ceased vedolizumab treatment, for poor response in all but one case.

The primary outcome, treatment success at week 14 (defined as steroid- and exclusive enteral nutrition-free remission without the need for new medications or surgical interventions), was achieved by 37% of UC children and 14% of CD children.

Remission rates at last follow-up were 39% for UC and 24% for CD.

Among children who had baseline and follow-up colonoscopic assessment, 15% of UC patients and 17% of CD patients achieved mucosal healing. Six of 25 children who had stool calprotectin measured at baseline and follow-up achieved deep remission.

There was no association between remission rates and gender, age at diagnosis, disease duration, CRP, presence of perianal disease, reason for previous anti-TNF failure, disease location in CD, or disease extent in UC.

Ten children (17%), four with CD and six with UC, underwent surgical resection at a median of four months.

There were no serious drug-related adverse events.

“In our cohort dosing was based on adult recommended dose with non-standardized, weight-based modifications in younger children,” the researchers note. “Since children weighing less than 30kg are best dosed by body surface area (BSA), until formal dosing is available it is reasonable to dose children in the equivalent of 300mg/1.73m2 (i.e., 175mg/BSA), and over 40kg as adults.”

“If vedolizumab is working, it should be continued,” Dr. Ledder said. “Similar to previous biological therapies, we don't necessarily have a planned cease date as long as it's effective. After a prolonged period of demonstrated deep healing, then there is room for discussion about a drug holiday. This is particularly the case in the patients in our study, the overwhelming majority of whom were very sick with multiple previous treatment failures.”

“We are still in the early days of understanding this new drug, and we need more data,” he said. “As newer medications start coming on-board over the next few years, we hope to improve our ability to predict which patients will respond to different treatment options to better direct appropriate treatment in a timely manner.”

The study had no external funding. Four of the 22 authors reported various relationships with Takeda, which manufactures vedolizumab.

SOURCE: http://bit.ly/2u5kHPt

J Crohns Colitis 2017.