Vedolizumab Maintenance Safe and Effective for Kids With IBD

Maintenance treatment with vedolizumab (Entyvio) appeared to be safe and effective in children with inflammatory bowel disease (IBD), with greater effectiveness in those with ulcerative colitis, according to a prospective cohort study.

At 54 weeks, 25% of children with Crohn’s disease and 47% of children with ulcerative colitis or unclassified IBD were in complete remission (OR 2.41, 95% CI 1.15-5.05), reported Dan Turner, MD, PhD, of Hebrew University of Jerusalem, and colleagues in Lancet Gastroenterology & Hepatology.

The median weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) score decreased from 35 at baseline to 13 (median of differences -14, 95% CI -33 to 0) at week 54, and the median Pediatric Ulcerative Colitis Activity Index (PUCAI) score decreased from 25 to 5 (median of difference -10, 95% CI -30 to 0).

“Our study suggests that vedolizumab is a viable option for induction and long-term maintenance therapy in children with IBD, particularly in those with ulcerative colitis,” the authors concluded.

Infliximab (Remicade) and adalimumab (Humira) are the only biologics approved for children with IBD; vedolizumab is often prescribed off-label. Despite its frequent use, prospective data for vedolizumab in kids are available for short-term induction outcomes only, Turner and team noted.

Of note, children who achieved therapeutic response or remission at week 6 (39%) were more likely than those who didn’t (15%) to reach sustained steroid-free and exclusive enteral nutrition-free clinical remission (OR 3.5, 95% CI 1.1-15.7). None of the children with moderate to severe Crohn’s at week 6 achieved sustained clinical remission, compared with 35% of those with mild Crohn’s or in clinical remission at week 6.

Other significant predictors of response at week 6 were hemoglobin, C-reactive protein (CRP), elevated CRP, erythrocyte sedimentation rate (ESR), elevated ESR, and albumin, Turner and team reported, but “wPCDAI remained the strongest predictor of sustained steroid-free and exclusive enteral nutrition-free clinical remission at week 6 with the optimal cutoff being 17.5 or lower.”

This study “represents a crucial advance in addressing treatment gaps for children with Crohn’s disease and ulcerative colitis,” wrote Elizabeth A. Spencer, MD, of the Icahn School of Medicine at Mount Sinai in New York City, in an accompanying editorial. “The favorable safety profile of vedolizumab is especially appealing to families and young patients, given that patients might require lifelong treatment.”

Spencer particularly drew attention to the finding that “a robust, early response is a strong predictor of long-term outcomes,” suggesting that “rapid treatment escalation could be warranted for children who still have clinically significant disease activity following induction.”

But Spencer also pointed out limitations of the findings. “The study did not investigate which children were most likely to benefit from escalated treatment intervals,” she wrote. The small number of children in the trial under 30 kg (15%) makes the utility of therapeutic drug monitoring in those patients uncertain, she added. Furthermore, the study did not provide data on vedolizumab’s effects on extraintestinal manifestations, such as joint issues.

This study, known as VEDOKIDS, involved 137 patients enrolled from 17 centers in six countries between May 2016 and April 2022. Of the patients, 54% were girls, and age at initiation of vedolizumab was an average 14; 47% had Crohn’s disease, 47% had ulcerative colitis, and 7% had unclassified IBD. The study excluded patients starting vedolizumab to prevent postoperative recurrence, and other medications were allowed, including immunomodulators, corticosteroids, and 5-aminosalicylic acids.

Following then-current recommendations, the study protocol advised an intravenous induction dose of 177 mg/m² of body surface area not to exceed 300 mg, with subsequent infusions at 2 and 6 weeks and maintenance infusions every 8 weeks, or less if needed. However, actual doses varied because children were managed according to local prescribing practices and at the treating physicians’ discretion without standardized dosing or dose-escalation criteria.

“This approach reflects real-world clinical practice and ensured that the study’s findings would be broadly applicable,” the authors wrote.

Complete remission was defined as a wPCDAI of

Patients who discontinued the drug before week 54 included 53% of those with Crohn’s and 26% of those with ulcerative colitis. About a quarter of patients had inadequate response, 5% underwent surgery, two patients stopped due to adverse events, and 7% were lost to follow-up. None of the children were dependent on steroids during the 54 weeks.

Among the 38 adverse events related to the drug in 21% of children, none were serious, and the most common were headache, myalgia, and fever.