Alena Skrahina1, Hennadz Hurevich2, Dennis Falzon3, Liudmila Zhilevich4, Valiantsin Rusovich5, Masoud Dara6, Svetlana Setkina7. 1. Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus. Electronic address: alena_skrahina@tut.by. 2. Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus. 3. Global Tuberculosis Programme, World Health Organisation, Geneva, Switzerland. 4. General Directorate of Medical Care, Ministry of Health, Minsk, Belarus. 5. Country Office, World Health Organisation, Minsk, Belarus. 6. Regional Office for Europe, World Health Organisation, Copenhagen, Denmark. 7. Centre for Examinations and Tests in Health Care, Minsk, Belarus.
Abstract
BACKGROUND/ OBJECTIVE: Outcomes of treatment for multidrug-resistant tuberculosis (MDR-TB) remain poor worldwide. Among patients with MDR-TB in Belarus who started treatment in 2012, only 54% completed it successfully, with treatment failure reported in 22% of the patients; additionally, 11% died and 13% were lost to follow-up or remained unevaluated. In Belarus, to improve outcomes, bedaquiline was introduced in MDR-TB treatment in June 2015. The national TB program developed measures to monitor safety and effectiveness of bedaquiline-containing regimens in line with the World Health Organization recommendations. METHODS: After enrollment of patients, clinical, radiological, laboratory, and microbiological data were carefully collected at start, during treatment, and at follow-up. A total of 197 patients were enrolled: male, 140 (71%); female, 57 (29%); new TB cases, 83 (42%); previously treated, 114 (58%); extensively drug-resistant-TB (XDR-TB), 128 (65%), pre-XDR-TB (fluoroquinolone resistant), 34 (17%), pre-XDR-TB (injectables resistant), 25 (13%), and other MDR-TB cases, 10 (5%). RESULTS: According to the intermediate analysis, 186 patients currently are continuing with the treatment, two patients died, and nine patients were lost to follow-up. Sputum culture conversion were observed in 186 patients (94%) at 6months and one (0.5%) of these 197 patients started treatment; six patients (3%) remain sputum culture positive. The safety data were as follows: 135 patients (68%) experienced metabolism and nutrition disorders (hyperuricemia being the most common), 127 patients (64%) experienced hepatobiliary disorders (hepatic functions abnormality being the most common), 93 patients (47%) experienced electrolyte disorders (hypomagnesemia being the most common), 80 patients (41%) experienced cardiac disorders (abnormal electrocardiogram and arrhythmia being the most common), 68 patients (35%) experienced gastrointestinal system disorders (nausea, vomiting, and abdominal pain being the most common disorders), 54 patients (27%) experienced blood and the lymphatic system disorders (low platelet count being the most common), 42 patients (21%) experienced renal and urinary disorders (creatinine clearance decrease being the most common), 40 patients (20%) experienced nervous system disorders (headache, dizziness, and paresthesia being the most common ones), 36 patients (18%) experienced skin and subcutaneous tissue disorders (rush and pruritus being the most common), 35 patients (17%) experienced ear and labyrinth disorders (tinnitus and decreased hearing being the most common ones), 32 patients (15%) experienced psychiatric disorders (insomnia being the most common disorder), and 30 patients (14%) experienced infections and infestations (candidiasis being the most common). The most adverse events were mild or moderate in severity and reversible. One death was possibly related to MDR-TB therapy. CONCLUSION: Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment.
BACKGROUND/ OBJECTIVE: Outcomes of treatment for multidrug-resistant tuberculosis (MDR-TB) remain poor worldwide. Among patients with MDR-TB in Belarus who started treatment in 2012, only 54% completed it successfully, with treatment failure reported in 22% of the patients; additionally, 11% died and 13% were lost to follow-up or remained unevaluated. In Belarus, to improve outcomes, bedaquiline was introduced in MDR-TB treatment in June 2015. The national TB program developed measures to monitor safety and effectiveness of bedaquiline-containing regimens in line with the World Health Organization recommendations. METHODS: After enrollment of patients, clinical, radiological, laboratory, and microbiological data were carefully collected at start, during treatment, and at follow-up. A total of 197 patients were enrolled: male, 140 (71%); female, 57 (29%); new TB cases, 83 (42%); previously treated, 114 (58%); extensively drug-resistant-TB (XDR-TB), 128 (65%), pre-XDR-TB (fluoroquinolone resistant), 34 (17%), pre-XDR-TB (injectables resistant), 25 (13%), and other MDR-TB cases, 10 (5%). RESULTS: According to the intermediate analysis, 186 patients currently are continuing with the treatment, two patients died, and nine patients were lost to follow-up. Sputum culture conversion were observed in 186 patients (94%) at 6months and one (0.5%) of these 197 patients started treatment; six patients (3%) remain sputum culture positive. The safety data were as follows: 135 patients (68%) experienced metabolism and nutrition disorders (hyperuricemia being the most common), 127 patients (64%) experienced hepatobiliary disorders (hepatic functions abnormality being the most common), 93 patients (47%) experienced electrolyte disorders (hypomagnesemia being the most common), 80 patients (41%) experienced cardiac disorders (abnormal electrocardiogram and arrhythmia being the most common), 68 patients (35%) experienced gastrointestinal system disorders (nausea, vomiting, and abdominal pain being the most common disorders), 54 patients (27%) experienced blood and the lymphatic system disorders (low platelet count being the most common), 42 patients (21%) experienced renal and urinary disorders (creatinine clearance decrease being the most common), 40 patients (20%) experienced nervous system disorders (headache, dizziness, and paresthesia being the most common ones), 36 patients (18%) experienced skin and subcutaneous tissue disorders (rush and pruritus being the most common), 35 patients (17%) experienced ear and labyrinth disorders (tinnitus and decreased hearing being the most common ones), 32 patients (15%) experienced psychiatric disorders (insomnia being the most common disorder), and 30 patients (14%) experienced infections and infestations (candidiasis being the most common). The most adverse events were mild or moderate in severity and reversible. One death was possibly related to MDR-TB therapy. CONCLUSION: Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment.