ABSTRACT
BACKGROUND: Signal strength for any drug-event combination can be determined using disproportionality analysis. Vemurafenib is a BRAF inhibitor approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of metastatic melanoma. This study aims to identify the signal strength of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with vemurafenib using disproportionality analysis in FDA database of Adverse Event Reporting System (FAERS). METHODS: Data were obtained from the public release of data in FAERS. The case/non-case method was adopted for the analysis of the association between vemurafenib use and DRESS. The data mining algorithm used for the analysis was the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE>1, PRR≥2 was considered as positive signal strength. RESULTS: A total of 7,171 reports for DRESS have been reported in the FDA database. Amongst which, 125 reports were associated with vemurafenib. A cumulative ROR of 17.72 (95% CI 14.83; 21.18) and PRR of 17.46 (95% CI 14.65; 20.81) were observed. Combination treatment of vemurafenib with cobimetinib had a higher number of reports (100) with ROR of 103.42 (84.13- 127.14) and PRR of 94.52 (78.26- 114.15). Four deaths were reported and the non-death serious reports included hospitalization, life-threatening, disability, and other serious events with 61, 11, 2 and 39 reports, respectively. CONCLUSION: Positive signal strength was observed for vemurafenib associated DRESS. The signal strength was higher for vemurafenib in combination with cobimetinib than vemurafenib alone. Health care professionals should be cautious about encountering serious adverse events and should report such events to the regulatory authorities.
Subject(s)
Adverse Drug Reaction Reporting Systems , Drug Hypersensitivity Syndrome , Databases, Factual , Drug Hypersensitivity Syndrome/diagnosis , Humans , United States/epidemiology , United States Food and Drug Administration , Vemurafenib/adverse effectsABSTRACT
Background Signal generation through data mining algorithms is an innovative and emerging field in pharmacovigilance. Early detection of safety signals is important for public health safety. However, the possibility of generating pseudo signals should not be overlooked. Objective Our study aimed to identify potential signals of aromatase inhibitors associated Osteonecrosis of Jaw and assess the possibilities of the safety signal to be a pseudo signal/false positive in FDA Adverse Event Reporting System (FAERS). Setting Spontaneously reported data in FAERS database. Methods Data for this study were obtained from the public release of data in FAERS. OpenVigil, a pharmacovigilance analytical tool was used to access FAERS data. Reporting Odds Ratio (ROR) was used to assess the relation between the drug and adverse event. A value of ROR-1.96SE > 1, (SE-standard error) was considered positive. Main outcome measure Signal strength. Results FAERS database had a total of 15,178 reports for Osteonecrosis of Jaw. Amongst which 617 reports were associated with aromatase inhibitors. Signal strength ROR (lower bound of the 95% CI) for letrozole, anastrozole and exemestane associated Osteonecrosis of Jaw without any background correction was 8.34, 6.64 and 15.14 respectively. Upon removing the reports of concomitantly administered drugs (bisphosphonates and denosumab), signal strength drastically decreased to 0.03, 0.36 and 0.47 for letrozole, anastrozole and exemestane respectively. The signal strength of bisphosphonates and denosumab associated Osteonecrosis of Jaw was not changed significantly upon removal of aromatase inhibitors. Conclusion Our study concluded that the signal generated for aromatase inhibitors associated Osteonecrosis of Jaw in FAERS database can be false positive. Careful background corrections with identification of those risk factors are imperative to exclude false positive results.
