Adalimumab vs Infliximab in Pediatric Patients With Crohn's Disease: A Propensity Score Analysis and Predictors of Treatment Escalation

Abstract

INTRODUCTION:Two antitumor necrosis factor therapies (infliximab [IFX] and adalimumab [ADA]) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up.METHODS:Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes.RESULTS:There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 [95% CI 0.31–1.28] P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88–15.40) and 6.15 (2.08–6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, [95% CI 2.41–11.18], P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis.DISCUSSION:Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation.

Adalimumab vs Infliximab in Luminal Pediatric Crohn's Disease: Comparable Outcomes in a Prospective Multicenter Cohort Study

“…Limited comparative effectiveness studies exist in children to date. Our results build on a recent comparative effectiveness study in children with CD that showed no difference in primary nonresponse between those treated with ADA or IFX (10). Our results also seem to be consistent with noncomparative pediatric studies.…”

Current Role of Monoclonal Antibody Therapy in Pediatric IBD: A Special Focus on Therapeutic Drug Monitoring and Treat-to-Target Strategies

“…The discontinuation rate was 3.2% per year due to a loss of response in a Canadian study [ 11 ]. Treatment outcomes suggest that patients with high disease activity in Crohn’s disease respond equally well to infliximab and adalimumab, although randomized controlled head-to-head studies are lacking [ 12 , 13 ]. After three months of treatment, infliximab induced significant mucosal healing and was associated with improvement in clinical disease scores in adults [ 14 ].…”

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab

“…A randomized clinical trial comparing the efficacy of infliximab to adalimumab in patients with IBD has not been performed, though several observational studies showed comparable efficacy in adults (13,14). Similar analyses comparing pediatric patients with CD or UC, treated with infliximab and adalimumab, showed comparable efficacy and safety (15)(16)(17)(18)(19). However, a retrospective study showed that in UC, adalimumab was less likely to induce mucosal healing when compared to infliximab (20).…”