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Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

ABSTRACT: PURPOSE:Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases. METHODS:Seven investigators completed three CAT (ALDEN, Naranjo, Liverpool) for 10 SJS/TEN cases. Each CAT categorized the causality of 30 potential drugs as definite/very probable, probable, possible, or doubtful/unlikely. An additional reviewer provided expert opinion by designating the implicated drug(s) for each case. A Kappa score was generated to compare CAT responses both by method (reliability of all 7 reviewers, by CATs) and by reviewer (reliability of the 3 CAT, by reviewer). A c statistic was calculated to assess validity. RESULTS:Inter-rater reliability by CAT was poor to fair: ALDEN 0.22, Naranjo 0.11, and Liverpool 0.12. Reliability was highest when causality classification was definite/very probable (0.16-0.41). Similarly, intra-rater reliability by reviewer was poor. When comparing the validity of the overall CAT to expert reviewer, area under the curve was highest for ALDEN (c statistic 0.65) as compared to Liverpool (0.55) or Naranjo (0.54). CONCLUSION:Available CAT have poor reliability and validity for drug-induced SJS/TEN. Due to the importance of determining ADR causality for research, industry, and regulatory purposes, development of an enhanced tool that can incorporate data from immunological testing and pharmacogenetic results may strengthen CAT usefulness and applicability for drug-induced SJS/TEN.

SUBMITTER: Goldman JL

PROVIDER: S-EPMC6659414 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

Goldman Jennifer L JL Chung Wen-Hung WH Lee Brian R BR Chen Chun-Bing CB Lu Chun-Wei CW Hoetzenecker Wolfram W Micheletti Robert R Yasuda Sally Usdin SU Margolis David J DJ Shear Neil H NH Struewing Jeffery P JP Pirmohamed Munir M

European journal of clinical pharmacology 20190327 8

<h4>Purpose</h4>Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases.<h4>Methods</h4>Seven investigators completed three CAT (ALDEN, Naranjo, Liv ...[more]

PMID: 30918988

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Project description:BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic emergencies. Although pregnant women comprise a subset of individuals at risk for SJS and TEN development, little is known with regard to outcomes and treatment.ObjectiveThis study aimed to conduct a systematic review to characterize the risk factors, outcomes, and treatment of SJS and TEN in pregnant patients and newborns.MethodsA primary literature search was conducted using PubMed in September 2019, using the following search terms entered in separate pairs: pregnant or pregnancy and stevens-johnson or SJS or toxic epidermal necrolysis. Reviews, studies in a language other than English, and articles not including pregnant patients were excluded.ResultsTwenty-six articles were included for review, including a total of 177 patients. The average maternal age for a reaction was 29.9 years, gestational age was 24.9 weeks, and time to reaction after drug initiation was 27.5 days. Approximately 85% of pregnant women in this review were infected with HIV. The most common causative medications were antiretroviral therapy (90% of all cases), antibiotics (3%), and gestational drugs (2%). Of the 94 cases in which outcome data were available, the survival rates of pregnant women and newborns after delivery were 98% and 96%, respectively. Withdrawal of the offending agent and supportive care was often sufficient for treatment, but antibiotics, steroids, and intravenous immunoglobulin were implemented in some cases. Complications included preterm labor, vaginal stenosis, and vaginal adhesions.ConclusionGiven the predominance of studies focusing on the subset of pregnant patients who are infected with HIV, SJS and TEN is most commonly reported in young patients after antiretroviral therapy, primarily nevirapine. Overall mortality is lower than that of the general population, but similar to the expected mortality rates of younger adults. Early recognition and withdrawal of the offending agent is essential to mitigate the distinct consequences of these conditions in the pregnant population.

Dataset Information

Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

Publications

Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

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