Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy

Background: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. Methodology: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer–Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). Results: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03–6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39–4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14–3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. Conclusion: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients. Author summary: Adverse events (AE) produced by the drugs used to treat leprosy can hinder the successful completion of the therapeutic regimen. Well-known AE produced by dapsone (DDS) are related to liver problems, allergic reactions, or to the destruction of red and/or white blood cells, causing anemia. Helping the physician to recognize a patient that may develop these adverse reactions can be useful. Thus, we developed a model to predict AE in patients with leprosy receiving standard World Health Organization-recommended multidrug therapy (WHO/MDT). Our question was whether we could use sociodemographic and clinical variables to generate a predictive model for DDS-ADEs. The model developed in this study could be a useful tool to assist physicians in predicting DDS-ADEs when treating patients with standard WHO/MDT for leprosy, and thus, establish a safer therapeutic plan for patients with a greater ADE risk.