Pediatric hepatic laboratory reporting with CFTR modulators: a FAERS pharmacovigilance study

Area of Science:

• Pharmacovigilance
• Pediatric Hepatology
• Drug Safety

Background:

• CFTR modulator labels warn of potential liver injury in children.
• Existing adverse event databases may conflate monitoring with actual injury.

Purpose of the Study:

• To determine if pediatric hepatic adverse event reports for CFTR modulators reflect laboratory monitoring or confirmed liver injury.
• To analyze the nature of hepatic reporting in children receiving CFTR modulators.

Main Methods:

• Analysis of FAERS/openFDA data for CFTR modulator reports, focusing on pediatric cases (age < 18).
• Comparison of broad hepatic terms (injury/failure + lab abnormalities) and narrow terms (explicit injury/failure).
• Calculation of Reporting Odds Ratios (ROR) with 95% Confidence Intervals (CIs) against all other openFDA reports.

Main Results:

• Pediatric broad hepatic reporting was increased (ROR 1.67), but serious broad hepatic reporting was not (ROR 1.08).
• Pediatric narrow hepatic reporting was below background levels (ROR 0.65).
• Commonly reported terms were elevated liver enzymes and bilirubin, indicating laboratory monitoring.

Conclusions:

• Pediatric FAERS data suggest a pattern of hepatic laboratory reporting, not increased clinical liver injury.
• Findings support current label-based monitoring practices and highlight the need for improved case documentation.
• Multicenter pediatric cohort studies are necessary for accurate incidence and treatment comparisons.