Postmarketing Safety Concerns With FDA Black Box Warning Monoclonal Antibodies: A Pharmacovigilance Study Based on...

To characterize the real-world safety profile of 23 monoclonal antibodies (mAbs) carrying US Food and Drug Administration (FDA) black box warnings (BBWs) by applying disproportionality analysis to safety reports in the FDA Adverse Event Reporting System (FAERS) from Q1 2021 to Q2 2025. Although mAbs have transformed the treatment of cancer, autoimmune, and rare diseases, several remain associated with serious or life-threatening adverse events (AEs) that warrant continuous postmarketing monitoring.

FAERS reports involving the 23 mAbs were screened for BBW-related AEs using MedDRA Preferred Terms. Each drug-event pair was analyzed through 2×2 contingency tables. Disproportionality signals were identified using the proportional reporting ratio (PRR), reporting odds ratio (ROR), chi-square (χ²), and 95% confidence interval (CI) for ROR. Bayesian analysis was also performed using the Bayesian Confidence Propagation Neural Network (BCPNN) approach to calculate the Information Component (IC) and its lower bound (IC₀₂₅). A signal was considered present when the PRR was ≥2, χ² value was ≥4, and at least 3 individual case safety reports (ICSRs) were available for a given drug-event pair. ROR signals were considered statistically significant when the lower bound of the 95% CI exceeded 1. In addition, BCPNN analysis was performed, and signals were considered significant when the lower limit of the 95% CI of the IC 025 was greater than 0. Temporal patterns in adverse event reporting were examined by summarizing FAERS reports and corresponding disproportionality metrics for each drug-event pair on a quarterly basis from Q1 2021 to Q2 2025. Changes across quarters were evaluated by directly comparing the number of reported cases and calculated signal measures between time periods. The study looked at patterns over time using simple comparisons, without using formal statistical techniques such as time-series analysis or regression modeling to test significance or predict trends.

Out of 13,462,218 total FAERS reports, 330,851 involved the 23 mAbs. The strongest signal was ipilimumab-immune-mediated dermatitis (PRR 232.12; ROR 250.41; IC₀₂₅ 4.21; χ² 4003.3). Panitumumab showed the highest Bayesian certainty for skin toxicity (IC₀₂₅ 4.61), and ipilimumab-immune-mediated enterocolitis had the highest χ² value (13,320.3). Reporting trends for most mAbs remained consistent over time, though immune checkpoint inhibitors demonstrated a gradual increase in signal intensity across quarters.

BBW-related adverse events for mAbs remain prominent in postmarketing data. Immune-related toxicities, especially with checkpoint inhibitors, show rising trends. However, as disproportionality analyses are based from reporting patterns of adverse events within the FAERS database rather than true incidence rates, the identified signals should be considered exploratory and warrant confirmation through well-designed pharmacoepidemiological studies. These findings reinforce the need for continued pharmacovigilance to support risk-benefit evaluation and patient safety.