Demographics, latency, and mortality of severe cutaneous adverse reactions in an FDA pharmacovigilance database

Summary: Adverse drug reactions (ADR) are a significant concern in medicine due to their potential to cause substantial morbidity and mortality. Among the most serious of ADRs are severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruption (GBFDE). These conditions differ in phenotype, causative drugs, demographics, and latency (time between administration and reaction). We used the FDA Adverse Event Reporting System (FAERS), a comprehensive database with millions of reports submitted by providers, patients, and manufacturers, applying disproportionality measures and machine learning to analyze these rare reactions at scale. After sanitization and deduplication, FAERS was queried from 2004 to 2003 for SCAR cases. A total of 56,683 cases were reported, with median age 53 years (interquartile range [IQR] 32-68), with significant differences in age between phenotypes. Over 200 drugs had positive disproportionality signals. SCAR reporting has increased over time, particularly to biologics and checkpoint inhibitors. Using random forest classifiers, we showed causative drug is the most influential variable on latency, followed by number of concomitant drugs, and mortality is most strongly tied to age and number of concomitant drugs, regardless of SCAR phenotype. This largest retrospective study of SCAR to date shows the variety of phenotypes, causative agents, demographic variables, latencies, and mortality in SCAR patients. Continued mining of these databases, retrospective analyses of electronic health records, and prospective data can expand upon these results, better characterize variations, and improve recognition and care for patients with SCAR. Eric M. Mukherjee^{1, 2}, Dodie Park¹, Michelle Martin-Pozo¹, Elizabeth J. Phillips^{1, 2, 3} 1. Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States. 2. Dermatology, Vanderbilt University Medical Center, Nashville, TN, United States. 3. Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia. Adaptive and Auto-Immunity