Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study.

Background: Infliximab and adalimumab are the only biologics thus far approved for paediatric patients with inflammatory bowel disease (IBD), so other biologics, such as vedolizumab, are prescribed off-label. Despite its frequent use, prospective data for vedolizumab treatment in children are available only for short-term induction outcomes. We aimed to evaluate the long-term efficacy and safety of maintenance therapy with vedolizumab in paediatric patients with IBD.

Methods: In this multicentre, prospective, cohort study (VEDOKIDS), children younger than 18 years with Crohn's disease, ulcerative colitis, or IBD unclassified (analysed with the ulcerative colitis group) who had initiated intravenous vedolizumab were enrolled from 17 centres in six countries (Israel, the USA, Italy, Ireland, Denmark, and Slovenia). Patients initiating vedolizumab to prevent postoperative recurrence were excluded. Vedolizumab dose or schedule were not standardised, and concomitant treatment with any other medication was permitted. Patients were prospectively followed up for 54 weeks, with repeated biosampling. The primary outcome was complete remission at week 54, defined as clinical remission (weighted Paediatric Crohn's Disease Activity Index [wPCDAI] of <12·5 points in Crohn's disease and Paediatric Ulcerative Colitis Activity Index [PUCAI] of <10 in ulcerative colitis) without the need for surgery, exclusive enteral nutrition for children with Crohn's disease, or steroids (steroid-free and exclusive enteral nutrition-free clinical remission) plus CRP concentration lower than 1·5 times the upper limit of normal (ULN) of 0·5 mg/dL. In cases of missing data on CRP, ESR was used instead (concentrations <1·5 times the ULN, which was 25 mm/h). Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT02862132.

Findings: Between May 19, 2016, and April 1, 2022, we enrolled 142 patients. Five children who had received only one or two infusions of their three-infusion induction before switching drugs due to COVID-19 pandemic-related reasons were excluded, leaving 137 children (64 [47%] with Crohn's disease, 64 [47%] with ulcerative colitis, and nine [7%] with IBD unclassified; 63 [46%] male and 74 [54%] female; age range of 0·7-17·6 years) in the intention-to-treat population. The median wPCDAI score in children with Crohn's disease decreased from 35 (IQR 18 to 49) at baseline to 13 (0 to 25; median of differences -14 [95% CI -33 to 0]) at week 54, and the median PUCAI score in children with ulcerative colitis decreased from 25 (IQR 15 to 50) at baseline to 5 (0 to 25) at week 54 (median of difference -10 [-30 to 0]). Improvements in disease activity were significant by week 6, with no further significant changes between visits. At week 54, 16 (25%) of 64 children with Crohn's disease and 34 (47%) of 73 with ulcerative colitis or IBD unclassified were in complete remission. 38 vedolizumab-related adverse events were recorded in 29 (21%) of 137 children, the most common being headache (n=7), myalgia (n=4), and fever (n=4), and none were serious.

Interpretation: Vedolizumab maintenance seems safe and efficacious in children, with a higher efficacy in those with ulcerative colitis than in those with Crohn's disease.

Funding: The European Crohn's and Colitis Organisation, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.