Многоцентровое наблюдательное неинтервенционное исследование применения комбинированных противотуберкулезных препаратов при лечении больных туберкулезом легких

The objective of the study: to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods. 13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results. Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer.Цель исследования: оценка в многоцентровом неинтервенционном наблюдательном исследовании результатов лечения больных туберкулезом с использованием комбинированных препаратов с фиксированными дозами, переносимости и безопасности этих препаратов.Материалы и методы. В исследовании, проходившем с 2016 по 2018 г., участвовали 13 противотуберкулезных учреждений. Сформированы первичная популяция (РР) из 489 пациентов, после применения критериев исключения – субпопуляция (subPP) из 267 пациентов с впервые выявленным туберкулезом легких и рецидивом, которые получали лечение по I или III режиму химиотерапии. Для статистической обработки данных использовали методы описательной статистики.Результаты. Из РР основной курс химиотерапии завершили 267 (54,6%) (subPP). Досрочно прекратили лечение 118 (24,1%) пациентов из 489. Первичная лекарственная устойчивость выявлена у 30 (6,1%) из 489, вторичная – у 74 (15,1%) из 489. В subPP прекращение бактериовыделения обнаруживалось к концу интенсивной фазы в 78 (96,3%) случаях из 81. Клинико-рентгенологическая динамика отмечалась в этой подгруппе в течение 106,2 ± 63,3 дня (медиана 90). Длительность интенсивной фазы в subPP составила 107,9 ± 50,5 дня. При оценке безопасности зарегистрировано 191 нежелательное явление (НЯ) у 149 (30,5%) из 489 пациентов. По степени тяжести большинство НЯ были легкой степени (164 из 191), реже (20 из 191) – средней степени и 7 – серьезные НЯ. С приемом исследуемых препаратов установлена связь при 61 НЯ у 57 (38,2%) из 149 пациентов. В структуре этих НЯ преобладало транзиторное повышение уровня трансаминаз (45 (73,8%) из 61 НЯ, но в единичном случае (1,6%) зарегистрирован лекарственный гепатит). Среди серьезных НЯ два случая благополучно разрешились к завершению протокола, два ‒ закончились летальным исходом при сочетании ВИЧ-инфекции и туберкулеза, а в трех случаях диагностированы онкологические заболевания

The multicenter observational non-interventional study of combination anti-tuberculosis drugs used in treatment of pulmonary tuberculosis patients

The objective of the study: to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods. 13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results. Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer