Retrospective Assessment of an Adalimumab Model-Informed Precision Dosing Support Tool for Use in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Therapeutic drug monitoring in pediatric inflammatory bowel disease (IBD) has been used to achieve and maintain remission. Few guidelines exist to aid clinicians in the adjustment of anti-tumor necrosis factor therapies. The objective was to assess the agreement between real-world postinduction and posteriori analysis of retrospective data, using 2 novel pharmacokinetic (PK) models for adalimumab. METHODS: A retrospective chart review was conducted in pediatric IBD patients treated with adalimumab. A Bayesian clinical decision support tool (InsightRX) was used. Postinduction serum concentration measurements of adalimumab were performed by drug-tolerant, homogenous shift mobility assay. Predicted serum adalimumab concentrations from both models were compared to the actual serum concentrations through a Bland-Altman analysis. Paired sample t test was used for equivalence. RESULTS: A total of 47 patients were included. Forty-one patients (87%) had Crohn disease, and 30 (64%) were male. Most were induced with 160 mg of adalimumab and maintained on 40 mg biweekly. No significant difference resulted between the de Klaver average prediction and mean population concentration (p = 0.294). Significant difference was observed between Ternant and mean population serum adalimumab concentration (p < 0.001). The Bland-Altman plot for the de Klaver method showed no proportional bias. Additionally, 49% of patients required a dose adjustment during maintenance therapy. CONCLUSIONS: The de Klaver model was able to provide less bias than the Ternant model and may aid in predicting serum adalimumab concentrations. Approximately half of the patients required dose adjustment during maintenance therapy to obtain a therapeutic drug concentration or achieve clinical remission.

Natural History of Pediatric Patients With Crohn's Disease Treated With Mesalamine Therapy.

Background: 5-aminosalicylates (5-ASA) are used to treat mild to moderate ulcerative colitis. Despite their lack of efficacy in Crohn disease (CD), they are still used in real-world practice. Additionally, when patients have progressive disease, they may escalate to biologic therapy, at which time 5-ASA may or may not be discontinued. Objectives: The aim of this study is to assess the clinical outcomes of patients started on 5-ASA for the treatment of pediatric CD. The secondary aims were to evaluate the outcomes of those who continue 5-ASA to those who discontinue 5-ASA upon biologic escalation. Methods: We performed a single-center retrospective chart review of pediatric CD patients from 2010 to 2019 who were initially treated with 5-ASA. Demographics, medication and laboratory data, and clinical disease activity were collected. Results: Sixty-one patients were included in the study; the majority had inflammatory CD with ileocolonic involvement. Twenty-four patients were on a concomitant immunomodulator. The majority of patients (85.2%) required escalation to biologics. Thirty-two patients (61.5%) who escalated to biologic therapy continued on 5-ASA. Eighty percent of patients achieved clinical remission at 1 year, and there was no difference between those who continued 5-ASA at time of biologic initiation compared to those who did not continue the medication. Patients who discontinued 5-ASA had an average annual cost savings of $6741. Conclusion: 5-ASA is not a durable monotherapy for the treatment of pediatric CD. Patients who require escalation from 5-ASA to biologic therapy do not benefit from concomitant 5-ASA therapy. Further prospective studies are needed to confirm these findings.

Comparison of Short-Term Outcomes for Standard Versus Nonstandard Induction Dosing of Infliximab for Pediatric Inflammatory Bowel Disease.

OBJECTIVE: Recent studies have emphasized the early use of infliximab (IFX) in pediatric patients with inflammatory bowel disease. Standard dosing of 5 mg/kg/dose may not be sufficient to achieve optimal clinical outcomes. The aim of our study was to compare short-term outcomes with standard dosing of IFX to higher, nonstandard dosing of IFX for induction therapy. METHODS: Retrospective study of 162 pediatric patients receiving either standard (5-6 mg/kg, n = 90) or nonstandard (>6 mg/kg, n = 72) dosing of IFX during induction was performed. Patient demographics, clinical outcomes, and laboratory data were collected. Need for dose escalation during the first 6 months, combination therapy with immunomodulators, and steroid-free progression were investigated. RESULTS: Clinical remission rates between the 2 groups were significantly different, with patients receiving nonstandard dosing demonstrating higher rates (58% vs 78%; p = 0.012). Use of combination therapy with immunomodulators was significantly different between standard and nonstandard groups (80% vs 48%; p < 0.001). Numeric trend in need for IFX dose escalation in the first 6 months was seen between standard and nonstandard groups (54% vs 39%, respectively; p = 0.087). Post-induction IFX trough concentrations, rates of antibody development, drug discontinuation, and infusion reaction were similar. CONCLUSIONS: Nonstandard induction dosing of IFX was associated with higher rates of clinical remission, despite similar rates of serum IFX trough concentrations. There was a numeric trend towards the standard group requiring dose escalation within the first 6 months of therapy. Patients given nonstandard dosing may achieve superior clinical outcomes compared with those on standard dosing.