Effectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses

Hdl Handle:
http://hdl.handle.net/10144/619003
Title:
Effectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses
Authors:
Ahmad Khan, F; Salim, M; du Cros, P; Casas, E; Khamraev, A; Sikhondze, W; Benedetti, A; Bastos, M; Lan, Z; Jaramillo, E; Falzon, D; Menzies, D
Journal:
The European Respiratory Journal
Abstract:
We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.
Publisher:
European Respiratory Society
Issue Date:
27-Jul-2017
URI:
http://hdl.handle.net/10144/619003
DOI:
10.1183/13993003.00061-2017
PubMed ID:
28751411
Submitted date:
2017-08-03
Language:
en
Description:
We regret that this article is behind a paywall.
ISSN:
1399-3003
Appears in Collections:
TB

Full metadata record

DC FieldValue Language
dc.contributor.authorAhmad Khan, Fen
dc.contributor.authorSalim, Men
dc.contributor.authordu Cros, Pen
dc.contributor.authorCasas, Een
dc.contributor.authorKhamraev, Aen
dc.contributor.authorSikhondze, Wen
dc.contributor.authorBenedetti, Aen
dc.contributor.authorBastos, Men
dc.contributor.authorLan, Zen
dc.contributor.authorJaramillo, Een
dc.contributor.authorFalzon, Den
dc.contributor.authorMenzies, Den
dc.date.accessioned2017-09-06T12:11:47Z-
dc.date.available2017-09-06T12:11:47Z-
dc.date.issued2017-07-27-
dc.date.submitted2017-08-03-
dc.identifier.citationEffectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses. 2017, 50 (1) Eur. Respir. J.en
dc.identifier.issn1399-3003-
dc.identifier.pmid28751411-
dc.identifier.doi10.1183/13993003.00061-2017-
dc.identifier.urihttp://hdl.handle.net/10144/619003-
dc.descriptionWe regret that this article is behind a paywall.en
dc.description.abstractWe assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.en
dc.language.isoenen
dc.publisherEuropean Respiratory Societyen
dc.titleEffectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analysesen
dc.identifier.journalThe European Respiratory Journalen

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