Identification of severe cutaneous reactions and genomic risk factors in users of antiepileptic drugs [poster]
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Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, lifethreatening cutaneous reactions that may occur following exposure to certain medications, including antiepileptic drugs (AEDs). No reliable incidence estimates of SJS/TEN for US populations have been calculated since the introduction of ICD-9 codes specific for SJS/TEN in October 2008. This study seeks to: 1) investigate the incidence of SJS/TEN using retrospective case identification, 2) test the positive predictive values of ICD-9 codes prior-/post-October 2008, and 3) pilot the feasibility of conducting a population-based pharmacogenomic study. Methods: With input from dermatologists, pharmacoepidemiologists, and pharmacogeneticists at FDA, HealthCore, and 11 HMORN sites, we validated ICD-9 codes associated with SJS/TEN in 3 cohorts : 1) patients with an inpatient code of 695.1x between 01/01/01–12/31/08; 2) codes 695.12–695.15 from 08/01/08-08/31/12; and 3) codes 279.5, 279.51, 279.53, 695.8, 695.81, 693.0x, 694.8x, 694.4x or diagnosis codes 692.9, E85x.x-E858.9, 693.8, 692.89, 695.89, 695.1x, 692.3x, 695.0 in an inpatient setting plus specific drug exposure between 01/01/01–08/31/12. We extracted a standardized clinical and laboratory dataset. A sample of 265 potential SJS/TEN cases at 5 sites was selected for adjudication by medical chart review. Statistical models will be created to estimate the total number of SJS/TEN cases at all sites based on the positive predictive value of the case identification algorithm. To pilot the feasibility of a pharmacogenomic study, we estimated the number of living cases available, contacted potential cases, and tested 100 random DNA samples from the Marshfield Clinic Personalized Medicine Research Project for HLAA* 3101/HLA-B*1502 alleles to establish a control source. Results: A total of 54,049 patients was identified from electronic records: 3,058 in cohort 1; 1,733 in cohort 2; and 49,258 in cohort 3. Potential cases (n=9) were identified and will be invited to participate in a genetic study. Among the 100 samples genotyped, 5 were positive for HLA-A*3101 and none were positive for HLA-B*1502, consistent with known frequencies. Conclusions: We identified a large number of potential SJS/TEN cases using code-based algorithms that will be used to determine the incidence of these events and to plan a larger follow-up study of specific AEDs and genomic factors.