Sara Rodríguez-Martín1,2,3, Elisa Martín-Merino4, Victoria Lerma1,3, Antonio Rodríguez-Miguel1,2,3, Olga González5, Carlos González-Herrada5, Elena Ramírez6, Teresa Bellón7, Francisco J de Abajo1,2,3. 1. Clinical Pharmacology Unit, Príncipe de Asturias University Hospital, Madrid, Spain. 2. Department of Biomedical Sciences, University of Alcalá, Madrid, Spain. 3. Pharmacoepidemiology Research Group, Institute for Health Research IRYCIS, Madrid, Spain. 4. Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency of Medicines and Medical Devices, Madrid, Spain. 5. Dermatology Department, University Hospital of Getafe, Madrid, Spain. 6. Clinical Pharmacology Department, La Paz University Hospital, Madrid, Spain. 7. Drug Hypersensitivity Laboratory, Institute for Health Research IdiPAZ, La Paz University Hospital, Madrid, Spain.
Abstract
PURPOSE: The "case-population" design has been proposed for the surveillance of rare events like Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), wherein a registry of cases is combined with sales data from the source population in order to estimate crude odds ratios (ORs). A major drawback of this method is the inability to distinguish between new and non-new users of drugs, which for the study of hypersensitivity reactions is of utmost importance. METHODS: We have explored an approach in which the exposure to the drugs of interest in the source population is inferred from a primary health care database (BIFAP), which helped us to identify drug initiators among all users and additionally adjust for potential confounders. A total of 44 SJS/TEN cases from the Registry and 44 000 controls randomly sampled from BIFAP and matched with cases for index date were included. We estimated the adjusted ORs (AORs) and 95% confidence intervals (CI) of SJS/TEN associated with the new use of 13 drugs (for which we had at least two exposed cases) through a conditional logistic regression model. RESULTS: AORs (95% CI) were estimated for phenytoin, 4618 (434-49112); cotrimoxazole, 1142 (163-8015); allopurinol, 160 (36-709); dexamethasone, 38 (1.33-1077); ibuprofen, 33 (8.6-124); lorazepam, 27 (5.8-124); paracetamol, 13 (2.8-62); levofloxacine, 12 (1.24-120); amoxicillin, 6.9 (1.39-35); pantoprazole, 6.5 (0.10-420); metamizole, 6.3 (0.69-57); amoxicillin clavulanic acid, 4.2 (0.53-34); and omeprazole, 1.34 (0.06-31). The inclusion of non-new users dramatically decreased the AORs for all drugs. CONCLUSIONS: The case-population approach using a registry of cases and a primary health care database proved feasible and efficient for the active surveillance of SJS/TEN.
PURPOSE: The "case-population" design has been proposed for the surveillance of rare events like Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), wherein a registry of cases is combined with sales data from the source population in order to estimate crude odds ratios (ORs). A major drawback of this method is the inability to distinguish between new and non-new users of drugs, which for the study of hypersensitivity reactions is of utmost importance. METHODS: We have explored an approach in which the exposure to the drugs of interest in the source population is inferred from a primary health care database (BIFAP), which helped us to identify drug initiators among all users and additionally adjust for potential confounders. A total of 44 SJS/TEN cases from the Registry and 44 000 controls randomly sampled from BIFAP and matched with cases for index date were included. We estimated the adjusted ORs (AORs) and 95% confidence intervals (CI) of SJS/TEN associated with the new use of 13 drugs (for which we had at least two exposed cases) through a conditional logistic regression model. RESULTS: AORs (95% CI) were estimated for phenytoin, 4618 (434-49112); cotrimoxazole, 1142 (163-8015); allopurinol, 160 (36-709); dexamethasone, 38 (1.33-1077); ibuprofen, 33 (8.6-124); lorazepam, 27 (5.8-124); paracetamol, 13 (2.8-62); levofloxacine, 12 (1.24-120); amoxicillin, 6.9 (1.39-35); pantoprazole, 6.5 (0.10-420); metamizole, 6.3 (0.69-57); amoxicillin clavulanic acid, 4.2 (0.53-34); and omeprazole, 1.34 (0.06-31). The inclusion of non-new users dramatically decreased the AORs for all drugs. CONCLUSIONS: The case-population approach using a registry of cases and a primary health care database proved feasible and efficient for the active surveillance of SJS/TEN.
Authors: Francisco J de Abajo; Sara Rodríguez-Martín; Victoria Lerma; Gina Mejía-Abril; Mónica Aguilar; Amelia García-Luque; Leonor Laredo; Olga Laosa; Gustavo A Centeno-Soto; Maria Ángeles Gálvez; Miguel Puerro; Esperanza González-Rojano; Laura Pedraza; Itziar de Pablo; Francisco Abad-Santos; Leocadio Rodríguez-Mañas; Miguel Gil; Aurelio Tobías; Antonio Rodríguez-Miguel; Diego Rodríguez-Puyol Journal: Lancet Date: 2020-05-14 Impact factor: 79.321