A real-world analysis of Lomitapide-associated adverse events: Data from FAERS and CVAROD
Bibliographic record
Abstract
Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor approved for the treatment of Homozygous Familial Hypercholesterolemia (HoFH), effectively lowers LDL cholesterol but raises safety concerns, particularly regarding hepatic and gastrointestinal adverse events (AEs). We conducted a pharmacovigilance disproportionality analysis using 2 major spontaneous reporting systems: the U.S. FDA Adverse Event Reporting System (FAERS, 2004-2024) and the Canada Vigilance Adverse Reaction Online Database (CVAROD, 2014-2025). All Lomitapide-related reports were extracted and analyzed using 4 statistical algorithms: reporting odds ratio (ROR), proportional reporting ratio, information component (IC), and Empirical Bayes Geometric Mean (EBGM). Signals were assessed at both the system organ class (SOC) and preferred term (PT) levels, with clinical priority scoring applied to rank AEs by relevance and impact. A total of 3665 FAERS and 80 CVAROD reports were analyzed. Gastrointestinal events were most frequent, including diarrhea (n = 1072; LBROR = 7.78), weight loss (n = 832; LBROR = 13.44), and nausea (n = 525; LBROR = 2.87). Hepatic events included elevated liver enzymes (n = 190; LBROR = 11.47) and hepatic steatosis (n = 67; LBROR = 13.01). Metabolic complications such as increased LDL levels (n = 159; LBROR = 85.45) were also observed. Subgroup analyses indicated higher susceptibility in males for diarrhea and weight loss, and in minors for abdominal pain (n = 10; LBROR = 7.53) and vomiting (n = 6; LBROR = 1.96). Novel signals, including renal pain (n = 10; LBROR = 2.33) and intestinal hemorrhage (n = 3; LBROR = 1.98), were identified, previously unreported in clinical trials. Most AEs occurred within the first week of treatment. Lomitapide is associated with clinically significant gastrointestinal, hepatic, and metabolic AEs, with elevated risk in male and pediatric patients. The early onset of reactions and emergence of novel signals highlight the importance of close monitoring, particularly during treatment initiation. Personalized risk mitigation strategies should be implemented to optimize the safety of Lomitapide therapy in HoFH patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.062 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".