Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach

Abstract

BACKGROUNDThe Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs.OBJECTIVEDescribe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial.RESULTSSkin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported.STUDY LIMITATIONSLoss of some monthly laboratory sample collection.CONCLUSIONSThere was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Hanseníase: perfil clínico-epidemiológico dos pacientes intolerantes ao tratamento padrão

“…Os dados foram tabulados em uma planilha de Ressalta-se ainda que, no diagnóstico, todos pacientes foram avaliados, mas na alta teve um porcentual de 32% de exames não realizados. A DDS foi o medicamento com maior índice de intolerância, esta é usada para tratamento de todas as formas de hanseníase em associação com outras drogas e é responsável por grande número de intoxicações 21 e uma das intercorrências mais frequentes é a anemia hemolítica, como descrito em outras pesquisas 14,20,[27][28][29][30] o que confirma os resultados deste estudo, pois 72,1% dos intolerantes a DDS apresentaram esta patologia. Sendo a hemólise resultado da diminuição da sobrevida eritroide, como consequência direta da grande quantidade de hemácias destruídas diariamente 30 .…”

Neurological Complications of Leprosy

“…83 Another study based in Brazil compared the adverse effect profile of U-MDT against traditional MDT, and found that patients receiving U-MDT had less reported anemia without other significant differences between the groups. 84 The findings of low relapse and reaction rates, acceptable adverse profiles, and high adherence rates make U-MDT potentially adaptable for national leprosy programs. Nonetheless, critics cite the short follow-up periods of relevant studies and question the necessity of changing from regimens that have proven highly successful for decades.…”

Unanswered questions on the safety of MDT-U

“…Sulfone syndrome (dapsone-induced hypersensitivity syndrome) was seen in one patient. 1 The key unanswered question remains: when during the course of therapy did these adverse events necessitating cessation of therapy occur? MDT-U consists of six months of dapsone, rifampicin, and clofazimine.…”