Greater Postinduction Infliximab Levels May Improve Pediatric CD Outcomes

Higher postinduction infliximab concentrations are independently associated with early clinical remission  and long-term clinical response (LTCR) in pediatric patients with Crohn disease (CD), according tostudy results published in American Journal of Gastroenterology.

Researchers reported post-hoc findings from the randomized controlled REACH trial, in which they evaluated the association between serum infliximab concentrations during and early after induction therapy and favorable short and long-term clinical outcomes in a pediatric population with CD.

The study participants had moderate to severe CD and received infliximab induction of 5 mg/kg at weeks 0, 2, and 6. At week 10, participants were randomly assigned to receive infliximab 5 mg/kg every 8 or 12 weeks through week 46. Participants without a clinical response were eligible to cross over 1 time to receive more frequent treatment and/or at a higher dose.

Outcomes were early clinical remission, which was a pediatric Crohn disease activity index (PCDAI) score of 10 or less assessed at week 10, and long-term clinical remission, which was a decrease in PCDAI score of at least 15 points, with a total score of 30 or less and no need for drug discontinuation assessed at weeks 30 and 54.

The cohort included 103 patients (median age, 13 years [IQR, 12-15 years]; 60.2% men; 82.5% White). The median disease duration was 1.8 years.

At week 10, clinical remission was achieved in 67 participants (65%). Greater infliximab concentration quartiles at weeks 6 and 10 were associated with an increased proportion of clinical remission at week 10. Receiver operating characteristic (ROC) analysis revealed an infliximab concentration threshold of 10.5 μg/mL at week 6 (area under ROC curve [AUROC], 0.64; 95% CI, 0.52-0.75) and 7.1 μg/mL at week 10 (AUROC, 0.62; 95% CI, 0.50-0.73) to significantly discriminate clinical remission at week 10.

Multivariable analysis demonstrated that infliximab concentration at week 10 was the only variable associated with early clinical remission at week 10 (odds ratio [OR] 1.54; 95% CI, 1.06-2.22; P =.022).

Long-term clinical remission was achieved in 71 participants (68.9%) at week 30. Greater infliximab concentration quartiles at week 10 were associated with an increased rate of long-term clinical remission at week 30. According to ROC analysis, an infliximab concentration threshold of 6.5 μg/mL was identified at week 10 (AUROC, 0.66; 95% CI, 0.54-0.78) to significantly discriminate LTCR at week 30.

Multivariable analysis revealed that infliximab concentration at week 10 (OR 1.62; 95% CI, 1.12-2.36; P =.010) and older age (OR 0.76; 95% CI, 0.61-0.93; P =.008) were the only variables that were associated with long-term clinical remission at week 30.

At week 54, long-term clinical remission was achieved in 77 patients (74.8%). Serum infliximab concentrations at weeks 6 and 14 were increased in the participants who had long-term clinical remission at week 54. Multivariable analysis was not conducted to determine variables independently associated with long-term clinical remission at week 54 because the univariate analysis did not reveal any statistically significant variables.

Study limitations include the absence of objective outcomes such as mucosal healing, and a causality between higher serum infliximab concentrations and improved outcomes cannot be established..

“Higher post-induction infliximab concentrations are associated with favorable early and long-term therapeutic outcomes in pediatric patients with CD,” conclude the researchers.

Disclosure: Some of the study authors declared affiliations with industry. Please see the original reference for a full list of authors’ disclosures.