TY - JOUR T1 - Standardised shorter regimens <em>versus</em> individualised longer regimens for multidrug-resistant TB JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01467-2019 SP - 1901467 AU - Syed Abidi AU - Jay Achar AU - Mourtala Mohamed Assao Neino AU - Didi Bang AU - Andrea Benedetti AU - Sarah Brode AU - Jonathon R. Campbell AU - Esther Casas AU - Francesca Conradie AU - Gunta Dravniece AU - Philipp du Cros AU - Denis Falzon AU - Ernesto Jaramillo AU - Christopher Kuaban AU - Zhiyi Lan AU - Christoph Lange AU - Pei Zhi Li AU - Mavluda Makhmudova AU - Aung Kya Jai Maug AU - Dick Menzies AU - Giovanni Battista Migliori AU - Ann Miller AU - Bakyt Myrzaliev AU - Norbert Ndjeka AU - Jűrgen Noeske AU - Nargiza Parpieva AU - Alberto Piubello AU - Valérie Schwoebel AU - Welile Sikhondze AU - Rupak Singla AU - Mahamadou Bassirou Souleymane AU - Arnaud Trébucq AU - Armand Van Deun AU - Kerri Viney AU - Karin Weyer AU - Betty Jingxuan Zhang AU - Faiz Ahmad Khan Y1 - 2019/01/01 UR - http://erj.ersjournals.com/content/early/2019/12/12/13993003.01467-2019.abstract N2 - 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% versus 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Mr. ABIDI has nothing to disclose.Conflict of interest: Dr. Achar has nothing to disclose.Conflict of interest: Dr. Assao Neino has nothing to disclose.Conflict of interest: Dr. Bang has nothing to disclose.Conflict of interest: Dr. Benedetti has nothing to disclose.Conflict of interest: Dr. Brode reports grants from Insmed, personal fees from Boehringer Ingelheim, personal fees from Astra-Zeneca, grants from Canadian Institutes for Health Research, outside the submmited work.Conflict of interest: Dr. Campbell has nothing to disclose.Conflict of interest: Dr. C. Casas has nothing to disclose.Conflict of interest: Dr. Conradie has nothing to disclose.Conflict of interest: Dr. Dravniece has nothing to disclose.Conflict of interest: Dr. du Cros reports he was previously a member of the Steering Committee and protocol writing committee for The PRACTECAL randomised controlled trial of 3 novel 6 month MDR-TB regimens. He 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: Dr. Falzon has nothing to disclose.Conflict of interest: Dr. Jaramillo has nothing to disclose.Conflict of interest: Dr. KUABAN has nothing to disclose.Conflict of interest: Dr. Lan has nothing to disclose.Conflict of interest: Dr. Lange reports personal fees from Chiesi, personal fees from Gilead, personal fees from Janssen, personal fees from Lucane, personal fees from Novartis, personal fees from Oxoid, personal fees from Berlin Chemie, personal fees from Thermofisher, outside the submitted work.Conflict of interest: Ms Li has nothing to disclose.Conflict of interest: Dr. Makhmudova has nothing to disclose.Conflict of interest: Dr. Maug has nothing to disclose.Conflict of interest: Dr. Menzies has nothing to disclose.Conflict of interest: Dr. Migliori has nothing to disclose.Conflict of interest: Dr. Miller reports and The Eli Lilly Foundation MDR-TB Partnership supported part of my salary in 2015–2016 through a grant to Salmaan Keshavjee, Harvard Medical School, although none of the work in this 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: Dr. Myrzaliev has nothing to disclose.Conflict of interest: Dr. NDJEKA has nothing to disclose.Conflict of interest: Dr. Piubello has nothing to disclose.Conflict of interest: Dr. SCHWOEBEL has nothing to disclose.Conflict of interest: Dr. Sikhondze has nothing to disclose.Conflict of interest: Dr. SINGLA has nothing to disclose.Conflict of interest: Dr. Souleymane has nothing to disclose.Conflict of interest: Dr. TREBUCQ has nothing to disclose.Conflict of interest: Dr. Van Deun has nothing to disclose.Conflict of interest: Dr. Viney has nothing to disclose.Conflict of interest: Ms. Zhang has nothing to disclose.Conflict of interest: Dr. Ahmad Khan reports grants from World Health Organisation during the conduct of the study.Conflict of interest: J. NoeskeConflict of interest: N. ParpievaConflict of interest: K. Weyer ER -