Abstract
We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).
We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Abstract
Standardised shorter regimens for RR/MDR-TB had substantially lower risk of loss to follow-up than individualised longer regimens, but also higher risk of failure or relapse if there was resistance to component drugs http://bit.ly/2RQgXzq
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00224-2020
This article has supplementary material available from erj.ersjournals.com
Author contributions: F. Ahmad Khan, D. Menzies, A. Benedetti, P. du Cros, J.R. Campbell, D. Falzon, Z. Lan, A. Piubello, V. Schwoebel and A. Trébucq designed the study and protocol. J. Achar, M.M. Assao Neino, A.K.J. Maug, D. Bang, S. Brode, E. Casas, F. Conradie, G. Dravniece, P. du Cros, C. Kuaban, A. Miller, B. Myrzaliev, G.B. Migliori, M. Makhmudova, J. Noeske, N. Ndjeka, A. Piubello, N. Parpieva, M.B. Souleymane, R. Singla, V. Schwoebel, W. Sikhondze and A. Trébucq contributed data to the meta-analysis. S. Abidi, F. Ahmad Khan, A. Benedetti, J.R. Campbell, P.Z. Li, Z. Lan, D. Menzies and B.J. Zhang did the data analysis. F. Ahmad Khan wrote the initial draft of the manuscript, and all authors provided critical input and revisions to the draft manuscripts, and approved the final manuscript.
Conflict of interest: S. Abidi has nothing to disclose.
Conflict of interest: J. Achar has nothing to disclose.
Conflict of interest: M.M. Assao Neino has nothing to disclose.
Conflict of interest: D. Bang has nothing to disclose.
Conflict of interest: A. Benedetti has nothing to disclose.
Conflict of interest: S. Brode reports grants from Insmed and the Canadian Institutes for Health Research, personal fees for educational presentations from Boehringer Ingelheim and AstraZeneca, outside the submitted work.
Conflict of interest: J.R. Campbell has nothing to disclose.
Conflict of interest: E. Casas has nothing to disclose.
Conflict of interest: F. Conradie has nothing to disclose.
Conflict of interest: G. Dravniece has nothing to disclose.
Conflict of interest: P. du Cros reports he was previously a member of the steering committee and protocol writing committee for the PRACTECAL randomised controlled trial of three novel 6-month MDR-TB regimens; and has undertaken a paid consultancy between TB Alliance and Burnet Institute to investigate applicability of the TB-Nix regimen (a novel short MDR-TB regimen) to Papua New Guinea.
Conflict of interest: D. Falzon has nothing to disclose.
Conflict of interest: E. Jaramillo has nothing to disclose.
Conflict of interest: C. Kuaban has nothing to disclose.
Conflict of interest: Z. Lan has nothing to disclose.
Conflict of interest: C. Lange reports personal fees for lectures from Chiesi, Gilead, Janssen, Lucane, Novartis, Oxoid, Berlin-Chemie and Thermo Fisher, outside the submitted work.
Conflict of interest: P.Z. Li has nothing to disclose.
Conflict of interest: M. Makhmudova has nothing to disclose.
Conflict of interest: A.K.J. Maug has nothing to disclose.
Conflict of interest: D. Menzies has nothing to disclose.
Conflict of interest: G.B. Migliori has nothing to disclose.
Conflict of interest: A. Miller reports that The Eli Lilly Foundation MDR-TB Partnership provided partial salary support in 2015–2016 through a grant to Salmaan Keshavjee, Harvard Medical School, although none of the work in the current paper or analysis was supported through that mechanism; the grant also paid for travel to a meeting in July of 2016.
Conflict of interest: B. Myrzaliev has nothing to disclose.
Conflict of interest: N. Ndjeka has nothing to disclose.
Conflict of interest: J. Noeske has nothing to disclose.
Conflict of interest: N. Parpieva has nothing to disclose.
Conflict of interest: A. Piubello has nothing to disclose.
Conflict of interest: V. Schwoebel has nothing to disclose.
Conflict of interest: W. Sikhondze has nothing to disclose.
Conflict of interest: R. Singla has nothing to disclose.
Conflict of interest: M.B. Souleymane has nothing to disclose.
Conflict of interest: A. Trébucq has nothing to disclose.
Conflict of interest: A. Van Deun has nothing to disclose.
Conflict of interest: K. Viney has nothing to disclose.
Conflict of interest: K. Weyer has nothing to disclose.
Conflict of interest: B.J. Zhang has nothing to disclose.
Conflict of interest: F. Ahmad Khan reports grants from the World Health Organization during the conduct of the study.
Support statement: This work was supported by the World Health Organization. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 23, 2019.
- Accepted December 4, 2019.
- The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2020.
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