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

• Published in: PLoS neglected tropical diseases Vol. 18; no. 1; p. e0011901
• Main Authors: de Araujo, Ana Carolina Galvão Dos Santos, Hacker, Mariana de Andrea Vilas-Boas, Pinheiro, Roberta Olmo, Illarramendi, Ximena, Durães, Sandra Maria Barbosa, Nobre, Maurício Lisboa, Moraes, Milton Ozório, Sales, Anna Maria, da Silva, Gilberto Marcelo Sperandio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-01-2024; Public Library of Science (PLoS)
• Subjects: Adult; Adverse and side effects; Anaemia; Anemia; Brazil - epidemiology; Care and treatment; Case-Control Studies; Classification; Clofazimine - therapeutic use; Complications and side effects; Confidence intervals; Dapsone; Dapsone - adverse effects; Diagnosis; Diaminodiphenylsulfone; DNA methylation; Dosage and administration; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Drugs; Education; Female; Females; Hemoglobin; Hemolytic anemia; Hepatotoxicity; Humans; Hypersensitivity; Infectious diseases; Leprostatic Agents - adverse effects; Leprosy; Leprosy - drug therapy; Medical records; Medicine and Health Sciences; Methemoglobinemia; Neutropenia; Nomograms; Outpatient care facilities; Patients; Physical Sciences; Prediction models; Research and Analysis Methods; Rifampin - therapeutic use; Risk factors; Sociodemographics; Statistical analysis; World Health Organization; Brazil
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011901

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.
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).
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.
We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.