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Analysis of immune checkpoint inhibitor-associated Stevens-Johnson syndrome/toxic epidermal necrolysis using the

Ziliang Zheng1,2, Zhu Shen1,2

  • 1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Cutaneous and Ocular Toxicology
|July 13, 2026
PubMed
Abstract

Insights

Immune checkpoint inhibitors (ICIs) can cause rare but fatal Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). PD-1/CTLA-4 inhibitors and combination therapies show increased SJS/TEN risk signals, necessitating careful monitoring.

Area of Science:

  • Pharmacovigilance
  • Oncology
  • Dermatology

Background:

  • Immune checkpoint inhibitors (ICIs) enhance anti-tumor responses but can cause immune-related adverse events.
  • Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, life-threatening dermatological reactions associated with ICIs.
  • Limited real-world data exists on ICI-induced SJS/TEN, highlighting the need for systematic pharmacovigilance.

Purpose of the Study:

  • To investigate the real-world reporting patterns of SJS/TEN associated with ICIs.
  • To identify and quantify risk signals for SJS/TEN linked to specific ICI agents and combinations.
  • To inform clinical risk prevention strategies for safe ICI medication.

Main Methods:

  • Analysis of SJS/TEN adverse event reports from the U.S. FDA Adverse Event Reporting System (FAERS) between 2011 and 2025.
  • Utilized OpenVigil 2.1 to calculate risk indicators, including the Reporting Odds Ratio (ROR), for PD-1, PD-L1, and CTLA-4 inhibitors.
  • Examined patient demographics, clinical characteristics, and outcomes, as well as concomitant medication use.

Main Results:

  • Identified 829 valid ICI-associated SJS/TEN cases, predominantly affecting elderly males (SJS/TEN) and females (overlapping SJS/TEN).
  • Observed a significant increase in SJS/TEN reports post-2016, coinciding with broader ICI utilization, and reported an overall fatality rate of 31.2%.
  • Detected significant risk signals for PD-1 (ROR=3.821) and CTLA-4 (ROR=3.677) inhibitors, with the PD-1+CTLA-4 combination exhibiting the strongest signal (ROR=4.784). Concomitant use of antibiotics and antibody-drug conjugates was associated with higher reporting frequencies.

Conclusions:

  • ICI-induced SJS/TEN, though rare, carries a high mortality risk.
  • PD-1/CTLA-4 inhibitors, particularly in combination regimens, present clear risk signals for SJS/TEN.
  • Concomitant medications may exacerbate SJS/TEN risks, emphasizing the need for early identification of high-risk patients and avoidance of adverse drug interactions to improve outcomes.
Keywords:
FAERSImmune checkpoint inhibitorsStevens–Johnson syndromepharmacovigilancetoxic epidermal necrolysis

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