Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil

Abstract

Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed. The effectiveness of clofazimine was assessed by comparing the treatment outcomes of patients undergoing clofazimine-containing regimens against those undergoing clofazimine-free regimens and its safety by describing clofazimine-attributed adverse events. A total of 1446 patients were treated with clofazimine-containing regimens and 1096 with pyrazinamide-containing regimens.Although success rates were similar in patients treated with clofazimine those treated with pyrazinamide (880 out of 1446, 60.9%, 708 out of 1096, 64.6%; p=0.054), clofazimine-treated cases exhibited higher death rates due to tuberculosis than pyrazinamide-treated ones (314 out of 1446, 21.7%, 120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%, 95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%, 151 out of 1096, 13.8%). No relevant differences were detected when comparing adverse events in patients treated with clofazimine-containing regimens to those treated with clofazimine-free regimens. However, the incidence of side-effects was less than previously reported (gastro-intestinal complaints: 10.5%; hyper-pigmentation: 50.2%; neurological disturbances: 9-13%).

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…78 Encouraging evidence is also available for a large programmatic study in Brazil. 79 Carbapenems may have a future role in the treatment of tuberculosis. However, a lack of an active oral formulation and the necessity of combining amoxicillin-clavulanate (to protect it from ß-lactamases) renders these compounds less appealing, even though some appear very active with excellent tolerability and safety.…”

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

“…Unfortunately, in countries where second‐line drugs have freely been used outside programmatic conditions, and those with high rates of more extensive patterns of drug resistance, this regimen would not be expected to work and indeed cannot be recommended. The available data shows that no more than 4% to 50% of patients in some MDR‐TB hotspots like Eastern Europe, South East Asia, Pakistan and Brazil are likely to be eligible for this regimen (Table ) …”

“…The available data shows that no more than 4% to 50% of patients in some MDR-TB hotspots like Eastern Europe, South East Asia, Pakistan and Brazil are likely to be eligible for this regimen (Table 2). [65][66][67][68][69][70]…”

Avances en el tratamiento de la tuberculosis multirresistente

“…también puede utilizarse en forma trisemanal a dosis de 1.200 mg cada 48 h, luego de la negativización del cultivo, como una forma de reducir la toxicidad. también podría usarse intermitente desde el inicio si el resto del esquema terapéutico es suficientemente robusto en fármacos activos [24][25] . 6.…”