Dataset Information

Quality Improvement Methodology Optimizes Infliximab Levels in Pediatric Patients with Inflammatory Bowel Disease.

ABSTRACT: Achieving and maintaining target serum trough infliximab levels improves outcomes in children and young adults with inflammatory bowel disease. Our goal was to improve adherence to an infliximab therapy guideline. The primary aim was to increase the percentage of patients with infliximab levels ≥5 μg/mL and results checked in the last 12 months from 73% to ≥80% from July 2017 to January 2018.

Methods

We participated in Intermediate Improvement Science Series, a course at Cincinnati Children's Hospital Medical Center designed to catalyze change using quality improvement methodology. We implemented interventions through plan-do-study-act cycles. Our outcome measure was balanced by 2 process measures to determine what actions impacted improvement. These measures included the percentage of infusion plans revised in response to a drug level <5 μg/mL and the proportion of plans for which a follow-up drug level was ordered.

Results

We increased the percentage of infusion plans revised before the next infusion from 63% to 87% and the percentage of plans that had an appropriate drug level recheck from 61% to 83% from July 2017 to January 2018. We increased the percentage of patients with an infliximab level >5 μg/mL, and results checked in the last 12 months, from 73% to 80%.

Conclusions

Quality improvement methodology was effective in improving provider adherence to infliximab therapeutic drug monitoring guidelines. Improvement in adherence to guidelines directly improved the percentage of patients achieving target infliximab levels at any time during infliximab therapy.

SUBMITTER: Hellmann J

PROVIDER: S-EPMC8104299 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany pediatric patients with inflammatory bowel disease (IBD) lose response to infliximab (IFX) within the first year, and achieving a minimal target IFX trough concentration is associated with higher remission rates and longer durability. Population pharmacokinetic (PK) modeling can predict trough concentrations for individualized dosing. The object of this study was to refine a population PK model that accurately predicts individual IFX exposure during maintenance therapy using longitudinal real-practice data.MethodsWe exported data from the electronic health records of pediatric patients with IBD treated with originator IFX at a single center between January 2011 and March 2017. Subjects were divided into discovery and validation cohorts. A population PK model was built and then validated.ResultsWe identified 228 pediatric patients with IBD who received IFX and had at least 1 drug concentration measured, including 135 and 93 patients in the discovery and validation cohorts, respectively. Weight, albumin, antibodies to IFX (ATI) detected by a drug-tolerant assay, and erythrocyte sedimentation rate (ESR) were identified as covariates significantly associated with IFX clearance and incorporated into the model. The model exhibited high accuracy for predicting target IFX trough concentrations with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% confidence interval [CI], 0.81-0.91) for population-based predictions without prior drug-level input. Accuracy increased further for individual-based predictions when prior drug levels were known, with an AUROC of 0.93 (95% CI, 0.90-0.97).ConclusionsA population PK model utilizing weight, albumin, ordinal drug-tolerant ATI, and ESR accurately predicts IFX trough concentrations during maintenance therapy in real-practice pediatric patients with IBD. This model, which incorporates dynamic clinical information, could be used for individualized dosing decisions to increase response durability.

Project description:Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients' ATI status.MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias.Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95% confidence interval (CI): 2.0-4.9, P<0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P<0.0001). Data only from patients with ulcerative colitis (n=86) exhibited a non-significant RR of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n=243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P<0.0001). A funnel plot suggested the presence of publication bias.The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.

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