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. 2022 Sep;56(5):794-801.
doi: 10.1111/apt.17092. Epub 2022 Jun 23.

Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix

Ohad Atia  1   2 , Gemma Pujol-Muncunill  3 , Víctor Manuel Navas-López  4 , Esther Orlanski-Meyer  1   2 , Oren Ledder  1   2 , Raffi Lev-Tzion  1 , Gili Focht  1   2 , Eyal Shteyer  1   2 , Ronen Stein  5 , Marina Aloi  6 , Richard K Russell  7 , Javier Martin-de-Carpi  3 , Dan Turner  1   2
Affiliations

Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix

Ohad Atia et al. Aliment Pharmacol Ther. 2022 Sep.

Abstract

Background: Patients enrolled in randomised controlled trials (RCTs) may differ from the target population due to restricted eligibility criteria.

Aim: To compare treatment response to biologics in routine practice for children with inflammatory bowel diseases (IBD) who would and would not have been eligible for enrolment in the regulatory RCT of the same drug.

Methods: We enrolled children with IBD who initiated adalimumab, infliximab, vedolizumab or ustekinumab. The eligibility criteria as defined in the RCT of the corresponding biologic were applied to each patient. The primary outcome was 12-month steroid-free remission (SFR) without switching biologics or undergoing surgery.

Results: We screened 289 children (198 [68%] with Crohn's disease [CD], 91 [32%] with ulcerative colitis [UC]) with 326 initiations of biologics. Only 62 of 164 (38%) children with moderate-to-severe disease would have been eligible for inclusion in the original RCTs. The SFR rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2-4.5]; p = 0.01). The main exclusion criterion was prohibited previous therapies (47%). Ineligible CD patients were older, more often had a family history of IBD and had higher levels of CRP than eligible children; in UC there were no differences between the groups.

Conclusion: Most children with IBD who initiate biologics would not have been eligible to be included in the corresponding regulatory RCTs. The outcomes of ineligible patients were worse than for eligible patients. Results from RCTs should be interpreted with caution when applied to clinical practice.

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Figures

FIGURE 1
FIGURE 1
Disease outcomes at 12 months in children with moderate–severe disease who were eligible and ineligible for inclusion in the original randomised controlled trials. Normal ESR <25 mm/h; normal CRP <0.5 mg/dl. SFR, steroid free remission.
FIGURE 2
FIGURE 2
Time from initiation of biologics to switching treatment in children with moderate–severe disease who were eligible vs ineligible for inclusion in the original randomised controlled trials.
FIGURE 3
FIGURE 3
Rate of clinical remission in the original RCTs and in the real‐world cohort stratified by disease and drug type. Remission rates were evaluated at 12 months for infliximab and adalimumab, and at 4 months for vedolizumab and ustekinumab, as done in the original RCTs.
See this image and copyright information in PMC

References

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