Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Data
2018
Autores
Ahmad, Nafees
Ahuja, Shama D
Akkerman, Onno W
Alffenaar, Jan-Willem C
Anderson, Laura F
Trajman, Anete
Journal Title
Journal ISSN
Volume Title
Publisher
The Lancet
Resumo
Background Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the
association of treatment success and death with the use of individual drugs, and the optimal number and duration of
treatment with those drugs in patients with multidrug-resistant tuberculosis.
Methods In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to
identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016.
We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis
published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment
completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised
individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics,
treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression,
we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific
drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment
duration.
Findings Of 12030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or
relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of
linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems
(0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10).
There was a significant association between reduced mortality and use of linezolid (–0·20, –0·23 to –0·16), levofloxacin
(–0·06, –0·09 to –0·04), moxifloxacin (–0·07, –0·10 to –0·04), or bedaquiline (–0·14, –0·19 to –0·10). Compared with
regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated
with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment
outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of
effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses,
heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although
relatively low for number of drugs and durations analyses.
Interpretation Although inferences are limited by the observational nature of these data, treatment outcomes were
significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and
carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to
ascertain the optimal combination and duration of these drugs for treatment of this condition.
Funding American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and
Prevention, European Respiratory Society, Infectious Diseases Society of America.
Description
Palavras-chave
Amikacin / therapeutic use, Antitubercular Agents / administration & dosage, Capreomycin / therapeutic use, Carbapenems / therapeutic use, Clofazimine / therapeutic use, Diarylquinolines / therapeutic use, Drug Therapy, Combination, Fluoroquinolones / therapeutic use, Humans, Kanamycin / therapeutic use, Levofloxacin / therapeutic use, Linezolid / therapeutic use, Moxifloxacin, Recurrence, Treatment Failure, Tuberculosis, Multidrug-Resistant / drug therapy*, Tuberculosis, Multidrug-Resistant / mortality*, Tuberculosis, Pulmonary / drug therapy*, Tuberculosis, Pulmonary / mortality*
Citação
Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JWC, Anderson LF, Trajman A et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. The Lancet. 2018 Sep 8;392(10150):821-834. doi: 10.1016/S0140-6736(18)31644-1.