Reações adversas aos medicamentos de dois esquemas de tratamento da hanseníase em um Centro de Referência Nacional do Brasil

Abstract

Introduction: The recommended standard treatment for leprosy is multidrug therapy (MDT/WHO), consisting of Rifampicin + Dapsone + Clofazimine. Other medications are recommended in cases of resistance, adverse reactions, and intolerances, including the ROM regimen, Rifampicin + Ofloxacin + Minocycline. Therefore, pharmacovigilance is an important tool for understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. Objectives: To evaluate ADRs by comparing two therapeutic regimens, standard MDT and ROM, used in the treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Materials and methods: A retrospective cohort study that assessed medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil, who underwent 24 months or more of treatment with MDT and ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity, and the causality criteria of Naranjo and WHO. D'Agostino-Pearson test, binomial test, Friedman test, Kaplan-Meier curves, and Cox time-dependent proportional hazard ratio regression were performed for multivariate analysis of prognostic factors. Results: Out of the total number of patients, 23.8% (103/433) experienced 134 ADRs during treatment, with an average of 1.3 reactions per patient. The median time for ADR onset was 79 days for MDT and 179 days for the ROM regimen. In the first reaction, Dapsone was the most frequently involved medication; the most affected systems were hematopoietic (36.8%; 38/103), gastrointestinal (21.3%; 22/103), and dermatological (17.4%; 18/103); 42.7% (44/103) were classified as mild, 26.2% (27/103) as moderate, and 31.1% as severe (32/103), with one resulting in death. In patients who experienced two or more ADRs, Rifampicin was the main causative drug; the affected systems were dermatological (43.3%; 10/23), gastrointestinal (30.4%; 7/23), and hematopoietic (13%; 3/23), with the majority classified as moderate (43.4%; 10/23) and mild (43.4%; 10/23). According to the Naranjo algorithm and WHO causality, most ADRs, both in the first and subsequent cases, were classified as probable and possible causes. The results indicated that the use of Clofazimine increased the risk of ADRs when combined with any other medication: 7% when used with Dapsone (HR: 1.07; p=0.866); 31% when used concurrently with Rifampicin (HR: 1.31; p=0.602); and 35% when used with Ofloxacin (HR: 1.35; p=0.653). On the other hand, Minocycline reduced the risk of ADRs by 44% (HR: 0.56; p=0.527) compared to Clofazimine, although statistical significance was not reached. The use of MDT conferred a 2.51 times higher risk of developing ADRs. All ADR cases were reported in VigiMed. Conclusion: MDT caused more ADRs compared to the ROM regimen, and these reactions were more severe, thereby providing less safety for patients undergoing this regimen. Dapsone was the medication that most commonly caused ADRs, followed by Rifampicin. The association with Clofazimine was associated with an additional risk of ADRs, necessitating further studies with larger caseloads to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to clinically and laboratorially monitor patients undergoing leprosy treatment with a focus on pharmacovigilance for timely diagnosis and management.