Abidi Syed, Achar Jay, Assao Neino Mourtala Mohamed, Bang Didi, Benedetti Andrea, Brode Sarah, Campbell Jonathon R, Casas Esther C, Conradie Francesca, Dravniece Gunta, du Cros Philipp, Falzon Dennis, 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 Jürgen, 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, Ahmad Khan Faiz
McGill International TB Centre, Montreal, QC, Canada.
Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Eur Respir J. 2020 Mar 20;55(3). doi: 10.1183/13993003.01467-2019. Print 2020 Mar.
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% 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.
我们试图比较世界卫生组织（WHO）推荐的两种治疗利福平耐药或耐多药（RR/MDR）结核病（TB）方案的有效性：一种9至12个月的标准化方案（“较短方案”）和≥20个月的个体化方案（“较长方案”）。我们从通过系统评价和公开征集数据确定的观察性研究中收集个体患者数据。我们纳入了符合WHO较短方案资格标准的患者：既往未接受过二线药物治疗，且对氟喹诺酮类和二线注射剂敏感的RR/MDR-TB。我们使用倾向得分匹配的混合效应meta回归来计算治疗失败或复发、治疗开始后12个月内死亡和失访的调整比值比和调整风险差异（aRDs）。我们纳入了9项较短方案研究中的3378名个体中的2625名（77.7%）和53项较长方案研究中的13104名个体中的2717名（20.7%）。较短方案的治疗成功率高于较长方案（合并比例80.0%对75.3%），原因是前者失访较少（aRD -0.15，95%CI -0.17至-0.12）。总体而言，较短方案治疗失败或复发的风险差异略高（aRD 0.02，95%CI 0至0.05），对吡嗪酰胺基线耐药时差异幅度更大（aRD 0.12，95%CI 0.07至0.16），对丙硫异烟胺/乙硫异烟胺（aRD 0.07，95%CI -0.01至0.16）或乙胺丁醇（aRD 0.09，95%CI 0.04至0.13）耐药时也是如此。在符合WHO使用标准的患者中，与个体化较长方案相比，标准化较短方案在治疗期间失访显著较少，但在对组成药物耐药时失败或复发较多。我们的研究结果支持改善获得可靠药物敏感性检测的必要性。
