Using data from the FDA Adverse Event Reporting System (FAERS) database, researchers identified the top drugs and drug classes linked to the development of Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN), as well as SJS/TEN-related mortality. These study findings were published in Clinical, Cosmetic and Investigational Dermatology.
The researchers conducted an analysis using data from the FAERS database from 2004 through 2021. A total of 24,976 patients were reported to have developed SJS/TEN, an adverse event (AE) as a result of one of these drugs or drug classes. In addition, 19.53% of SJS/TEN AEs resulted in patient mortality. Among patients for whom country information was available (n=22,191), 38.34% of those who developed SJS/TEN as a result of these drugs or drug classes were identified to be in the United States.
The top 50 drugs associated with the development of SJS/TEN accounted for approximately 61% of all cases. Among the 50 drugs identified, top drug classes linked to SJS/TEN were antiepileptics (19.37% of all reported AEs during the study period), nonsteroidal anti-inflammatory drugs (NSAIDs; 13.97% of all reported AEs), and antigout drugs, specifically allopurinol. Other associated drug classes included quinolones, lactam antibiotics, macrolides, proton pump inhibitors (PPIs), antivirals, monoclonal antibodies, and antidepressants. The drug most commonly associated with SJS/TEN AEs across the study period was lamotrigine (accounting for 9.63% of all SJS/TEN AEs reported in FAERS).
Increasing trends over time for drug classes associated with the development of SJS/TEN included monoclonal antibodies and PPIs, as well as immunosuppressants, diuretic drugs, selective calcium channel blockers, and antimalarial drugs.
The development of SJS/TEN resulted in fatal outcomes in 19.53% (4878) of patients. The top drug classes associated with SJS/TEN-related mortality in 2021 were monoclonal antibodies (23.94%) and antineoplastic agents (10.75%). Overall, the annual number of deaths reported to the FDA increased over time, from 85 to 326 between 2004 and 2021.
Categorized by drug class, SJS/TEN-related mortality was highest among patients treated with antiepileptic drugs, but the ratio of SJS/TEN mortality to total SJS/TEN cases among patients treated with antiepileptics was low.
The highest ratio of SJS/TEN-related mortality to the total number of SJS/TEN cases was associated with antineoplastic agents and cephalosporins. The researchers cautioned that the risk of developing SJS/TEN as a direct result of the use of cephalosporins may be underestimated. They noted that, despite cephalosporin agents being ranked outside the top 50 drugs causing SJS/TEN between 2004 and 2021, cephalosporin ceftazidime accounted for 60.61% of all cephalosporin-caused SJS/TEN mortality during this period.
The annual percentage of SJS/TEN AEs as a result of treatment with monoclonal antibodies increased from 0.00% in 2004 to 4.79% in 2021 (annual increase rate, 0.25%; 95% CI, 0.18-0.32). In 2021, monoclonal antibodies were associated with the highest percentage of SJS/TEN-related mortality (23.94% vs 0% in 2004), followed by antineoplastic agents (10.75% vs 1.08% in 2004). The antigout drug allopurinol accounted for the fastest-growing single drug-related SJS/TEN AEs across the study period (annual increase rate, 0.32%; 95% CI, 0.22-0.42).
In the US, treatment with lactam antibiotics or PPIs was reported in less than 15% of SJS/TEN AEs, and all other drug classes were in the range of 20% to 53%. Among the top 50 drugs, valdecoxib, phenytoin, celecoxib, and sulfamethoxazole/trimethoprim were reported to be associated with more than 60% of SJS/TEN AEs in the US. Diclofenac, acetylsalicylic acid, piperacillin/tazobactam, and lansoprazole were reported to be associated with less than 10% of SJS/TEN AEs in the US.
The study has several limitations, including the high risk for selection and reporting bias; the reliance on data submitted to the FDA, which may not provide an accurate estimate of the true amount of drug-related SJS/TEN AEs; and lack of availability of racial data among these patients.
The researchers concluded, “Through our examination of publicly available FAERS data, we have identified important themes and trends in drug-related SJS/TEN reactions. Monoclonal antibodies and proton pump inhibitors are emerging trends. Additionally, cephalosporin antibiotics may have a higher mortality rate following SJS/TEN. Although our reports are limited due to the voluntary nature of FDA FAERS reporting, they raise awareness of important issues and can be used to guide SJS/TEN researchers in generating hypotheses related to potentially important drugs.”
References:
Fei W, Shen J, Cai H. Causes of drug-induced severe cutaneous adverse reaction epidermal necrolysis (EN): an analysis using FDA Adverse Event Reporting System (FAERS) database. Clin Cosmet Investig Dermatol. Published online August 16, 2023. doi:10.2147/CCID.S422928
