Pediatr Gastroenterol Hepatol Nutr.  2020 Mar;23(2):121-131. 10.5223/pghn.2020.23.2.121.

Long-Term Efficacy of Anti-Tumor Necrosis Factor Agents in Pediatric Luminal Crohn's Disease: A Systematic Review of Real-World Evidence Studies

Affiliations
  • 1Amsterdam University Medical Centers, Location VU Medical Centre, Amsterdam, Netherlands.
  • 2Department of Paediatric Gastroenterology, Hepatology and Nutrition, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands. p.f.van.rheenen@umcg.nl

Abstract

PURPOSE
To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review.
METHODS
An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation.
RESULTS
In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83-97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67-91% and 61-85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy.
CONCLUSION
This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.

Keyword

Infliximab; Adalimumab; Survival analysis; Systematic review; Treatment outcome; Pediatrics; Crohn disease

MeSH Terms

Adalimumab
Child
Cohort Studies
Crohn Disease*
Humans
Infliximab
Necrosis*
Pediatrics
Phenobarbital*
Survival Analysis
Treatment Outcome
Adalimumab
Infliximab
Phenobarbital
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