Vedolizumab helps induce steroid-free remission in children with IBD

Use of vedolizumab as maintenance treatment in children with inflammatory bowel disease (IBD) results in sustained steroid-free remission, with an acceptable safety profile, according to the results of the 54-week follow-up of the VedoKids Study presented at ESPGHAN 2024.

Specifically, 40 percent of children with ulcerative colitis (UC) and 23 percent of those with Crohn’s disease (CD), potentially 40 percent in isolated CD, have achieved remission.

“Unlike the common notion that vedolizumab takes forever until it works, we saw rapid improvement just as we showed for the interim analysis, and children not achieving at least response by week 6 have low likelihood of entering remission thereafter,” said lead investigator Dan Turner, Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel.

In the VedoKids Study, Turner and his team explored the efficacy, safety, and dosing of vedolizumab in a large multicentre prospective cohort of children with IBD. Those with UC or CD initiated vedolizumab and were followed through 1 year at 17 international centres.

Turner and colleagues previously reported the interim analysis of 14-week induction treatment and saw improvement of disease activity both in CD and UC. The initial findings on the recommended dosing was 10 mg/kg or 200 mg per body surface area, up to 300 mg.

In the current analysis, the investigators performed a 54-week follow-up visit and evaluated the primary outcomes of sustained steroid- and exclusive enteral nutrition-free remission at both weeks 30 and 54. All analyses were intention-to-treat, and data were imputed based on the modified nonresponsive mutation methods.

A total of 137 children aged 2‒18 years (n=23, 16 percent <30 kg; n=44, 31 percent <40 kg) were included in the analysis. Of these, 73 had UC and 64 had CD.

“In UC, we saw … a rapid improvement in disease activity by week 6 and thereafter, [and] there was no significant change until week 54,” Turner said. “In CD … [there] might be a gradual decrease in disease activity over time, [but] the only significant change was, just like [in] UC, between baseline and week 6.”

Of the children with CD, 23 percent achieved the primary outcome. In terms of the more stringent outcomes (ie, steroid-free remission with low calprotectin and MINI index <8 points, reflecting endoscopic healing), on average, 25 percent of the participants achieved these. For those with UC, 40 percent achieved sustained steroid-free remission.

“If you want to average this with the steroid-free remission with low calprotectin, so it’s more or less 35 percent,” Turner said. “The difference between CD and UC was significant.”

Clinical response

The best predictor of sustained steroid-free remission was clinical response to vedolizumab.

“Patients [who] did not show any response, let alone remission at 6 weeks, had very low likelihood to achieve steroid-free remission down the road, especially CD,” Turner said.

Other variables that could potentially predict outcomes were also evaluated. Similarly, the strongest predictors both in CD and UC patients were clinical response or clinical disease activity at baseline.

With regard to safety, 197 adverse events (AEs) occurred in 78 children (57 percent), but only 11 were believed to be associated with vedolizumab treatment. None of the AEs were severe, with no deaths recorded (0 percent).

One case of Hodgkin’s lymphoma was reported, but it was not related to the study drug. Vedolizumab was then resumed in the child after completing the chemotherapy. Additionally, two children (1.5 percent) discontinued treatment with vedolizumab due to AEs (one infusion reaction and one leukocytoclastic vasculitis).