Methods:
For this study we used the data available in the U.S Food and Drug
Administration Adverse Reporting System (FAERS). This public
pharmacovigilance monitoring database contains adverse reports events,
medication error reports, and product quality complaints reported by
health care professionals, manufacturers, and consumers worldwide since
1968; providing case identification numbers, name of the medication,
adverse reaction, severity of the reaction, manufacturer of the
pharmaceutical, concomitant pharmaceuticals and other related
information. Since this is an anonymous database there was no need for
ethical committee approval for this study.
In the present study we comprehensively evaluated the cardiovascular
complications of the newly FDA approved anti-multiple sclerosis agents,
selective sphingosine-1-phosphate receptor modulator (fingolimod,
siponimod, ozanimod, ponesimod), humanized anti-CD20 monoclonal antibody
(ocreluzimab, ofatumumab) and humanized anti CD-25 monoclonal antibody
(Daclizumab). We looked for cardiovascular adverse events (AEs) using
standardized medical terms according to the Medical Dictionary for
Regulatory Activities, the list of terms included “atrial
fibrillation”, “congestive cardiac failure, cardiac failure
congestive”, “ventricular dysfunction”, “systolic dysfunction”;
“diastolic dysfunction”, “cardiac disfunction”, “cardiac failure”,
“cardiomyopathy”, “myocardial infarction”, “angina pectoris”,
“coronary artery disease”, “coronary artery occlusion”, “angina
unstable”, silent myocardial infarction, “acute coronary syndrome”
and were organized in these main groups.
The association between the use of SPR1 modulators and humanized
monoclonal antibodies with cardiovascular adverse events was assessed by
disproportionality signal detection analysis using the reporting odds
ratio (ROR). ROR is a measure of the magnitude of association between an
exposure to a given pharmaceutical agent and the odds of patients
experiencing a specific adverse event, compared to the odds of the same
event occurring with all other pharmaceutical agents in the database.
ROR was considered significant when the lower limit of the 95%
confidence interval (CI) was >1.0.