Vedolizumab Safe, Efficacious for Inducing Remission in Children With IBD

Vedolizumab should be considered for reducing remission in children with IBD, especially those with ulcerative colitis.

Vedolizumab was safe and efficacious for inducing remission in children with inflammatory bowel disease (IBD) at 14 weeks, especially for those who had ulcerative colitis (UC), according to a study in The Lancet Gastroenterology & Hepatology.

Researchers reported preliminary results from the induction phase to week 14 of the VEDOKIDS trial (ClinicalTrials.gov Identifier: NCT02862132), a pediatric, prospective cohort study conducted in 17 centers in 6 countries, including the United States. The participants were children aged 0 to 18 years with Crohn disease (CD), UC, and unclassified IBD, who initiated vedolizumab at any stage of their disease.

The children were managed based on local prescribing practices without standardization of dosing or criteria for escalation, although the study protocol suggested dosing of 177 mg/m² body surface area, up to 300 mg maximum. Infusions were scheduled at baseline and 2, 6, and 14 weeks. A stool sample was obtained at baseline and 14 weeks to assess fecal calprotectin, and serum samples were collected before each vedolizumab infusion.

Steroid-free and exclusive enteral nutrition-free clinical remission at 14 weeks was the primary outcome. Clinical remission was defined as a weighted Pediatric Crohn Disease Activity Index (wPCDAI) of less than 12.5 points in children with CD and a Pediatric Ulcerative Colitis Activity Index (PUCAI) of less than 10 in those with UC.

Vedolizumab seems effective in children with IBD, with potentially better results in patients with ulcerative colitis than in those with Crohn disease and in those with milder disease severity.

A total of 142 children (female, 54%; mean age [SD], 13.6[3.6] years) were included, of whom 65 (46%) children had CD, 68 (48%) had UC, and 9 (6%) had unclassified IBD. Of the cohort, 120 (85%) children weighed 30 kg or more.

At 6 weeks, 24 (34%) of 71 children with UC were in steroid-free and exclusive enteral nutrition-free clinical remission, as were 32 (42%) of 77 children at 14 weeks. In addition, 11 (18%) of 61 children with CD were in steroid-free and exclusive enteral nutrition-free remission at 6 weeks, as were 21 (32%) of 65 children at 14 weeks. The median PUCAI score in children with UC and median wPCDAI score in children with CD decreased significantly from baseline to week 14.

Of 56 children who provided a stool sample at week 14, 10 (18%) were in steroid-free and exclusive enteral nutrition-free clinical remission with a calprotectin concentration of less than 250 µg/g.

The participants had a median drug concentration of 24.7 µg/mL (IQR, 15.8-33.5) at week 6 and 9.1 µg/mL (3.8-16.2) at week 14. At weeks 6 and 14, drug concentrations were greater in patients who had UC vs those with CD, despite similar dosing.

Among children who weighed less than 30 kg, the dose required to reach the optimal drug concentration at week 6 (>25 µg/mL) was 200 mg/m² body surface area (area under the curve, 0.63 [95% CI, 0.32-0.94]).

A total of 114 adverse events were reported at week 14 in 32 (23%) children, with headache (5 [4%]), myalgia (4 [3%]), and fever (3 [2%] the most common. No cases of malignancy, progressive multifocal leukoencephalopathy, or death were reported.

Study limitations include the relatively small sample size of children weighing less than 30 kg and the absence of endoscopic assessment. Also, referral bias of the included centers is possible, which could limit generalizability.

“Vedolizumab seems effective in children with IBD, with potentially better results in patients with ulcerative colitis than in those with Crohn disease and in those with milder disease severity,” the researchers wrote.

Disclosure: This research was supported in part by Takeda. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References:

Atia O, Shavit-Brunschwig Z, Mould DR, et al. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study. Lancet Gastroenterol Hepatol. Published online October 25, 2022. doi:10.1016/S2468-1253(22)00307-7