Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis

Syed Abidi, Jay Achar, Mourtala Mohamed Assao Neino, Didi Bang, Andrea Benedetti, Sarah Brode, Jonathon R. Campbell, Esther C. Casas, Francesca Conradie, Gunta Dravniece, Philipp du Cros, Dennis Falzon, Ernesto Jaramillo, Christopher Kuaban, Zhiyi Lan, Christoph Lange, Pei Zhi Li, Mavluda Makhmudova, Aung Kya Jai Maug, Dick MenziesGiovanni Battista Migliori, Ann Miller, Bakyt Myrzaliev, Norbert Ndjeka, Juergen Noeske, Nargiza Parpieva, Alberto Piubello, Valerie Schwoebel, Welile Sikhondze, Rupak Singla, Mahamadou Bassirou Souleymane, Arnaud Trebucq, Armand Van Deun, Kerri Viney, Karin Weyer, Betty Jingxuan Zhang, Faiz Ahmad Khan

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
Article number1901467
JournalEuropean Respiratory Journal
Volume55
Issue number3
Number of pages13
ISSN0903-1936
DOIs
Publication statusPublished - 2020

Keywords

  • TREATMENT OUTCOMES
  • MYCOBACTERIUM-TUBERCULOSIS
  • CHAINED EQUATIONS
  • DRUG-RESISTANCE
  • SUSCEPTIBILITY
  • BEDAQUILINE
  • IMPUTATION
  • 1ST

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