Development of a predictive model for meglumine antimoniate treatment failure in patients with cutaneous leishmaniasis: Aretrospective cohort study

Background: Although alternative therapies for cutaneous leishmaniasis (CL) are available, systemic meglumine antimoniate (MA) remains the first-line treatment in many endemic regions. Its use is nevertheless associated with serious adverse effects and a high risk of treatment failure (TF). This study aimed to identify clinical and sociodemographic risk factors for TF following systemic MA therapy, which may enhance therapeutic decision-making and improve clinical outcomes. Methodology: We evaluated a retrospective cohort of 296 patients with CL treated with MA between 2007 and 2024. A multivariable logistic regression model was performed using candidate variables selected via clinical relevance, biological plausibility, stepwise selection and least absolute shrinkage and selection operator (Lasso) regression. Model performance was assessed through discrimination, calibration, and internal validation. Results were reported as odds ratios, 95% confidence intervals and p-values. Principal Findings: All included patients received first line MA therapy and completed at least six months of follow-up. Independent predictors associated with TF were age, occupational activity, size, number and anatomical location of lesions, clinical form, regional lymphadenopathy, and prior history of leishmaniasis. The final model showed moderate overall performance with a Hosmer-Lemeshow p value = 0.667, AUC = 0.691, and a Brier score of 22.8. Internal validation yielded a Harrel C = 0.608. Conclusions: The present study demonstrates an association between TF and socio-demographic, clinical variables. Identifying these risk factors may support clinical decision-making and contribute to optimizing treatment outcomes. Author summary: Cutaneous leishmaniasis is a parasitic disease that causes skin lesions that remains an important health problem in many parts of the world. Although alternatives therapies exist, systemic meglumine antimoniate remains the most used treatment in many countries. However, its clinical utility is frequently limited by severe adverse effects and a high risk of therapeutic failure we evaluated a historical cohort of patients treated with meglumine antimoniate between 2007 and 2024 to identify predictors of treatment failure. Our findings show that treatment was less successful in patients who were younger, living in rural place, prolonged disease duration, with multiple lesions, and prior history of leishmaniasis. Recognizing these factors can guide clinician in selecting optimized treatments and improve care for people with cutaneous leishmaniasis.