Aim The incidence of paediatric inflammatory bowel disease (PIBD) is rising and there is a lack of available licensed therapy options for children who have failed first line conventional therapy.¹ Vedolizumab and ustekinumab are expensive second-line non-anti-TNF biologic therapies that have improved health outcomes for patients with paediatric inflammatory bowel disease (PIBD), however, evidence is lacking, they are not commissioned by NHS England and are therefore used off-license.^{2 3}

This study aimed to evaluate treatment sequencing patterns of vedolizumab and ustekinumab to help guide future management of PIBD.

Methods This study was a single-centre, retrospective observational case note review of 29 PIBD patients. Patients were eligible for the study if they had a confirmed paediatric diagnosis of Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBDU) and were prescribed vedolizumab or ustekinumab or a combination of the two between 1st July 2018 and 31st March 2023. Demographic data alongside pharmacological history of biologic therapies and reasons for treatment changes were collected and analysed.

Patient data was collected using the electronic databases ‘Cerner’, ‘Evolve’, and ‘LastWord Legacy’. All data were collated and analysed on Microsoft Excel and IBM SPSS Statistics software.

Results At the primary endpoint, 77.78% of CD (n = 18) and 45.55% of UC (n = 11) patients had remained on non-anti-TNF biologics. Most patients in CD and UC cohort were on combination therapy of a biologic plus an immunosuppressant. All CD patients were started on anti-TNF therapy, however, two UC patients were initiated on a non-anti TNF, vedolizumab. as their initial biologic treatment. Overall, the CD population had a larger variety of sequencing patterns and had the most therapy lines, with four patients receiving four separate biologic therapy lines, and one patient receiving five. The median duration of time spent on vedolizumab was 1.65 years and 0.79 years for CD and UC respectively. The median duration of time spent on ustekinumab was 0.98 years for CD. Only one UC patient received ustekinumab and this was stopped on first dose due to an adverse reaction.

Conclusion Vedolizumab and ustekinumab provide further treatment options for PIBD patients, by delaying the need for surgical intervention. The high percentage (78.57%) of CD patients on ustekinumab at primary endpoint possibly suggests CD patients may tolerate ustekinumab better. No patterns between the number of biologic therapy lines administered and the frequency of patients remaining on non-anti-TNF therapy were recognised. The high variation in therapeutic sequencing, especially in CD, suggests a lack of treatment optimization. The low frequency of adverse reactions reported suggests a good safety profile of these medications in PIBD.

References

1. Conrad MA, Rosh JR. Pediatric inflammatory bowel disease. Pediatric Clinics of North America. 2017;64:577–591.

2. NHS England. Clinical Commissioning Policy: Ustekinumab for refractory Crohn’s disease in pre-pubescent children [Internet]. 2020 https://www.england.nhs.uk/publication/ustekinumab-for-refractory-crohns-disease-in-pre-pubescent-children/ (Accessed 22 July 2023).

3. NHS England. Clinical Commissioning Policy: Vedolizumab for refractory ulcerative colitis in pre-pubescent children [Internet]. 2020 https://www.england.nhs.uk/publication/vedolizumab-for-refractory-ulcerative-colitis-in-pre-pubescent-children/ (Accessed 22 July 2023)