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Preprint
Immune Checkpoint Inhibitors as Independent and Synergistic Drivers of SJS/TEN: A FAERS-Based Analysis
medRxiv : the preprint server for health sciences
Cold Spring Harbor Laboratory
30/06/2025
PMID: 40630567
Abstract
Importance; Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare, potentially fatal adverse drug reactions. As the use of immune checkpoint inhibitors (ICIs) expands, their role as direct inducers or synergistic contributors to SJS/TEN remains incompletely characterized.
Objective: To determine whether ICIs are independent risk factors for SJS/TEN, evaluate their interactions with known culprit drugs, and assess their impact on latency and mortality.
Design: Cross-sectional analysis of adverse event reports submitted to the U.S. Food and Drug Administration Adverse Event Reporting System (FDA FAERS) between January 2013 and December 2023, sanitized and de-duplicated. Logistic regression and Cox models were used to assess predictors of SJS/TEN development, mortality, and latency.
Setting: Global pharmacovigilance reports submitted to FAERS.
Participants: A total of 17,495 unique and de-identified patients reported SJS/TEN, of 13,986,839 total reports.
Exposures: Suspected causative drugs, including ICIs.
Main Outcomes and Measures: Primary outcomes were the adjusted odds of developing SJS/TEN, time-to-event (TTE) of reaction/drug latency, and all-cause mortality. Depending on the analysis, covariates included age, sex, number of concomitant drugs, cancer diagnosis, and specific drug exposures.
Results: Of 17,495 SJS/TEN cases (median age 53 years, 37.6% male), 970 (5.5%) had ICI exposure and 653 (3.7%) listed an ICI as the primary suspect. ICI exposure was associated with developing SJS/TEN (adjusted OR, 6.69; 95% CI, 6.19-7.23) while controlling for age, exposure to strong and weak culprits, number of concomitant drugs, and cancer diagnosis. ICI increases SJS-TEN risk among patients exposed to allopurinol (OR, 4.35; 95% CI, 3.12-6.06) and TMP-SMX (OR, 5.68; 95% CI, 4.05-7.95) with the same covariates. Among patients with small-molecule-induced SJS/TEN, mortality was strongly associated with ICI exposure (particularly exposure to multiple ICI, OR, 7.31; 95% CI, 3.09-17.27). Among all SJS/TEN cases, ICI exposure was associated with delayed onset, compared to cancer patients not exposed to ICI and non-cancer patients (median 20 vs 14 vs 13 days; P < .0001).
Conclusions and Relevance: ICIs are associated with increased SJS/TEN risk, both independently and in combination with known culprit drugs, and may delay disease onset. These findings support increased vigilance in prescribing known culprits alongside ICI.
Details
- Title
- Immune Checkpoint Inhibitors as Independent and Synergistic Drivers of SJS/TEN: A FAERS-Based Analysis
- Authors/Creators
- Eric Milan Mukherjee - Vanderbilt University Medical CenterDodie Park - Vanderbilt University Medical CenterMatthew S Krantz - Vanderbilt University Medical CenterCosby A Stone, Jr - Vanderbilt University Medical CenterMichelle Martin-Pozo - Vanderbilt University Medical CenterElizabeth Phillips - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia
- Publication Details
- medRxiv : the preprint server for health sciences
- Publisher
- Cold Spring Harbor Laboratory; United States
- Grant note
- R01 AI152183 / NIAID NIH HHS P50 GM115305 / NIGMS NIH HHS R01 HG010863 / NHGRI NIH HHS R21 AI139021 / NIAID NIH HHS D43 TW010559 / FIC NIH HHS U01 AI154659 / NIAID NIH HHS
- Identifiers
- 991005799071107891
- Copyright
- The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Preprint
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