Standardised shorter regimens individualised longer regimens for multidrug-resistant TB.

Standardised shorter regimens individualised longer regimens for multidrug-resistant TB.

Abidi, Syed;Achar, Jay;Neino, Mourtala Mohamed Assao;Bang, Didi;Benedetti, Andrea;Brode, Sarah;Campbell, Jonathon R;Casas, Esther;Conradie, Francesca;Dravniece, Gunta;du Cros, Philipp;Falzon, Denis;Jaramillo, Ernesto;Kuaban, Christopher;Lan, Zhiyi;Lange, Christoph;Li, Pei Zhi;Makhmudova, Mavluda;Maug, Aung Kya Jai;Menzies, Dick;Migliori, Giovanni Battista;Miller, Ann;Myrzaliev, Bakyt;Ndjeka, Norbert;Noeske, Jűrgen;Parpieva, Nargiza;Piubello, Alberto;Schwoebel, Valérie;Sikhondze, Welile;Singla, Rupak;Souleymane, Mahamadou Bassirou;Trébucq, Arnaud;Van Deun, Armand;Viney, Kerri;Weyer, Karin;Zhang, Betty Jingxuan;Khan, Faiz Ahmad;
The European respiratory journal 2019
268
abidi2019standardisedthe

Abstract

We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: 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 tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up.We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% 75.3%), due to less loss to follow-up with the former (aRD, -0.15 95%CI: -0.17 to -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: -0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 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 as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.

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