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

PLoS Negl Trop Dis. 2024 Jan 25;18(1):e0011901. doi: 10.1371/journal.pntd.0011901. eCollection 2024 Jan.

Abstract

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.

MeSH terms

  • Adult
  • Brazil / epidemiology
  • Case-Control Studies
  • Clofazimine / therapeutic use
  • Dapsone / adverse effects
  • Drug Therapy, Combination
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Humans
  • Leprostatic Agents / adverse effects
  • Leprosy* / drug therapy
  • Rifampin / therapeutic use
  • World Health Organization

Substances

  • Dapsone
  • Leprostatic Agents
  • Rifampin
  • Clofazimine

Grants and funding

The work was financially supported by CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico (URL: https://www.gov.br/cnpq/pt-br, Grant number: 312802/2020-0 to ROP), FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (URL: https://www.faperj.br/, Grant number: E-26/201.176/2021 (260734) to ROP), and FIOCRUZ - Fundação Oswaldo Cruz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.