(073) Purine antimetabolites associated pneumocystis jiroveci pneumonia among autoimmune and cancer population

Publication Number: 1068

Background: Purine antimetabolites (PA’s), structural analogues of purine bases, are agents widely used among autoimmune and the cancer population, but the association of pneumocystis jiroveci pneumonia with these agents is not well known.

Objectives: To detect the possible safety signal of purine antimetabolites associated with pneumocystis jiroveci pneumonia, stratifying among autoimmune and cancer population, through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.

Methods: A case/non-case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1-2021Q3) and the demographics isolated through the FAERS public dashboard (2004-2021). All purine antimetabolites were included in the analysis and Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR-1.96SE>1 and PRR2 with an associated X2 value of 4 or more was considered the threshold for a signal.

Results: A total of 7073 reports associated with pneumocystis jiroveci pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.69-16.91) (p < 0.001) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63
(17.42-22.13); 19.45(13.21-28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population and excluding the effect of glucocorticoids revealed a ROR of 3.15(2.83-3.51) and 2.93(2.26-3.79) respectively, with azathioprine having a ROR of 6.31(4.28-9.30) among the autoimmune population. The highest risk of PJP with the use of these agents was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57
(9.16-14.62)]. We hypothesized that the adverse event occurs due to the decline in the activation of the PI3K/AKT/mTOR pathway by purine antimetabolites, thus ultimately leading to a decrease in innate immunity.

Conclusions: Our study provided real-world evidence on the occurrence of PJP with the use of various purine antimetabolites, specifically among the autoimmune and cancer population. Given the wide use of these agents in at-risk population, it is important for clinicians to know about the potential possibility of PJP with these agents. More research with a superior epidemiological study design of these population is required to validate these findings.