(P-547) Aromatase Inhibitors Associated with Sjogren’s Syndrome: A Disproportionality Analysis in Spontaneous Reporting Database

Background: Sjogren’s Syndrome is an autoimmune disorder with characteristic signs of dry mouth and dry eyes. Aromatase inhibitors are a class of drugs used in the treatment of breast cancer. They may also be used off-label to reduce estrogen conversion when using external testosterone.

Objectives: This study aims to detect the possible safety signal of aromatase inhibitors associated with Sjogren’s Syndrome through disproportionality analysis in FDA Adverse Event Reporting System (FAERS) Database.

Methods: The case/non-case retrospective disproportionality analysis was adopted for this study. The publicly available FAERS data were used for analysis and data extraction and curation was done through OpenVigil 2.0, a pharmacovigilance platform to access FAERS for signal detection. The preferred term used for the study was “Sjogren’s syndrome” and Anastrozole, Letrozole and Exemestane were the drugs included in the analysis. Reporting odds ratio (ROR) and Proportional Reporting Ratio (PRR) were used as the data mining algorithm (DMA) for this analysis. A value of ROR-1.96SE >1 (SE-standard error) and PRR≥2, with an associated χ2 value of 4 or more was considered as the threshold for a signal. Open vigil 2.1 was used for data extraction and curation.

Results: FAERS database had a total of 1826 reports associated with Sjogren’s syndrome. Out of which 60 reports were associated with Aromatase inhibitors. The number of reports for Anastrozole, Letrozole and Exemestane were 26,32 and 2 respectively. Significant signals were obtained for Anastrozole and Letrozole associated Sjogren’s syndrome with ROR 8.642 (95%CI=5.866-12.731) and PRR 8.629 (5.861:12.705) for Anastrozole and with ROR 7.145 (5.036;10.137) and PRR 7.137 (5.036;10.137) for Letrozole respectively. Exemestane is associated with an insignificant safety signal (ROR 0.946). No reports were associated with other aromatase inhibitors such as Vorozole, Formestane, Fadrozole, Testolactone and Aminoglutethimide.

Conclusions: The results showed an association between Sjogren’s syndrome with Anastrozole and Letrozole. Although a causal relation cannot be proved, the number of cases reported and significant signal strength of the drug-event combination suggests that there might be an association. The findings of this study should be investigated using superior study designs before clinical application.