Post-marketing reporting patterns and disproportionality signals of mycophenolate mofetil: a pharmacovigilance study using the FAERS Database.

BACKGROUND

Mycophenolate mofetil (MMF) is widely used in solid-organ transplantation and autoimmune diseases. Spontaneous-reporting databases may assist in identifying adverse-event reporting patterns that warrant further clinical evaluation. This study characterized MMF-associated reports in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS

FAERS reports submitted from the first quarter of 2004 through the fourth quarter of 2024 were analyzed. After deduplication, reports listing MMF as the primary suspect drug were included. Medication-use, therapeutic-response, product-related, administrative, and outcome-only Preferred Terms were excluded from the primary clinical adverse-event signal analysis. Disproportionality was evaluated using the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and Multi-item Gamma Poisson Shrinker. Time-to-onset distributions were described only for reports with valid treatment-start and event dates.

RESULTS

A total of 44,671 MMF primary-suspect reports were included, of which 32,577 (72.9%) were classified as serious and 5589 (12.5%) included a reported fatal outcome. Valid time-to-onset information was available for 5433 reports (12.2%). Among this subset, 1333 reports (24.5%) had a recorded onset within 30 days, and 1978 (36.4%) had a recorded onset more than 360 days after treatment initiation. These proportions describe the distribution of reports with complete dates and do not represent incidence or time-dependent risk. Prominent reporting associations involved opportunistic infections and hematologic abnormalities, although substantial confounding by transplantation status, underlying disease, and concomitant immunosuppressive therapy remained.

CONCLUSIONS

FAERS reports involving MMF showed disproportionality associations for several clinically relevant events. These findings indicate reporting patterns rather than causal relationships or estimates of clinical risk. The time-to-onset findings were based on a small subset of reports with complete dates and should be interpreted descriptively. Confirmation using indication-specific longitudinal datasets with reliable exposure denominators is required. Key Points • Four complementary disproportionality methods were used to prioritize MMF-associated reporting signals in FAERS. • Non-clinical medication-use and therapeutic-response terms were separated from clinical adverse-event signals. • Time-to-onset information was available for only 12.2% of reports and was interpreted as a descriptive reporting distribution. • Confounding by indication and concomitant immunosuppressants limits attribution of the detected signals to MMF.