Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil.
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-1(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 clofazimineversusthose treated with pyrazinamide (880 out of 1446, 60.9%,versus708 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%,versus120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%,versus95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%,versus151 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%).
Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.|These authors contributed equally.
Margareth
M
Dalcolmo
Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.|These authors contributed equally.
Regina
R
Gayoso
Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari, Sassari, Italy giovannibattista.migliori@icsmaugeri.it.|These authors contributed equally.
Giovanni
0000-0002-1600-4474
G
Sotgiu
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri IRCCS, Tradate, Italy.|Public Health Consulting Group, Lugano, Switzerland.|These authors contributed equally.
Lia
L
D'Ambrosio
Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.
Jorge L
JL
Rocha
Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.
Liamar
L
Borga
National Mycobacteriology Laboratory, Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.
Fatima
F
Fandinho
Dept of Epidemiology, Escola Nacional de Saúde Pública (ENSP), Fundação Oswaldo Cruz (Fiocruz)/Ministry of Health, Rio de Janeiro, Brazil.
Jose U
JU
Braga
Division of Tuberculosis, State Secretariat of Health, São Paulo, Brazil.
Vera M N
VM
Galesi
Tuberculosis Unit, UNITAID, Geneva, Switzerland.
Draurio
D
Barreira
National Tuberculosis Control Programme, Secretaria de Vigilância em Saúde (SVS)/Ministry of Health, Brasilia, Brazil.
Denise A
DA
Sanchez
National Tuberculosis Control Programme, Secretaria de Vigilância em Saúde (SVS)/Ministry of Health, Brasilia, Brazil.
Fernanda
F
Dockhorn
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri IRCCS, Tradate, Italy.
Rosella
R
Centis
Dept of Pneumology, General Hospital of Gran Canaria "Dr Negrin", Las Palmas, Spain.|Dept of Tuberculosis, The Union (The International Union against Tuberculosis and Lung Disease), Paris, France.
Jose A
JA
Caminero
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri IRCCS, Tradate, Italy.
Giovanni B
0000-0002-2597-574X
GB
Migliori
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001938:Brazil / Q000453:epidemiology; D002991:Clofazimine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D002991:Clofazimine