A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Abstract

Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN. E ven 100 years after it was first reported (1), Chagas disease remains a serious public health problem in Latin America, with a high social and economic burden (2, 3). Moreover, the prevalence of Chagas disease is increasing, mainly due to migration, in countries where it is not endemic, such as the United States and European countries (4-7).Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease (8, 9), and the parasitological cure rate when patients are treated with BZN during the acute phase of the disease is almost 80% (10, 11). Although BZN effectiveness during the chronic phase of the disease remains uncertain (12)(13)(14), there is compelling evidence supporting the beneficial use of BZN even during the chronic phase of Chagas disease (13, 15), and some international guidelines are now advocating the use of BZN even among adults with chronic disease (16-18). However, adverse drug reactions (ADRs) occur in 30% to 87% of the patients treated with BZN (19-21), and 12% to 29% of patients fail to complete their full course of treatment (19-21). Therefore, the development of tools to identify patients with high probabilities of developing ADRs to BZN is highly desirable, as this strategy would improve compliance to BZN treatment and minimize complications (21,22).Logistic regression (LR) is a method often used to predict outcomes in health studies (23,24), and...

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