Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study

Abstract

Introduction Diabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM. Methods The study of patients with MDR/XDR-TB with or without DM (enrolled February 2018–September 2019, 21 Chinese hospitals) was supervised by the New Drug Introduction and Protection Program (NDIP). Of 640 patients with MDR/XDR-TB receiving BDQ-containing anti-TB treatments, two propensity score-matched groups (107 DM/107 non-DM) were compared for cumulative culture conversion rate, time to culture conversion, adverse events, and corrected QT interval. Results Body mass index was higher in patients with DM than patients without DM (23.29 ± 3.9 vs. 20.5 ± 3.6, P < 0.001); lung cavity prevalence (86.9% vs. 72.9%, P = 0.037) was also higher in patients with DM; the non-DM group had higher hepatitis prevalence (29.0% vs. 15.9%, P = 0.022). No significant intergroup differences were found for sputum culture conversion rate at week 8 (80.0% vs. 81.4%, P = 0.884), at week 24 (95.6% vs. 98.2%, P = 0.629), or for median time to sputum culture conversion [56 days (IQR 28–63) vs. 56 days (IQR 28–84) ( P = 0.687)]. Favorable post-24-week treatment outcomes were presented by 90.7% and 93.5% in the DM group and non-DM group, respectively, without significant intergroup differences ( P = 0.448). The DM adverse event rate exceeded non-DM rate (77.6% vs. 64.5%, P = 0.035). Conclusion Despite some differences in baseline characteristics, Chinese patients with MDR/XDR-TB with or without DM had similar sputum culture conversion rates and favorable treatment outcomes post-24-week BDQ-containing anti-TB treatment. Low BMI but not DM is risk factor associated with unfavorable outcome of patients with MDR/XDR-TB. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00396-9.

Bedaquiline-containing regimens and multidrug-resistant tuberculosis: a systematic review and meta-analysis

“… Author Year Country Type of study Mean/ median age HIV+, n (%) Previously treated for TB TB disease No. of patients receiving BDQ Other drugs included in the regimen Duration of treatment (months) Outcomes Treatment success Treatment failure Death Koirala et al 11 2021 Multicenter PC 39 27 (5.7) 329 MDR/XDR 383 WHO-recommended regimen 6 284 11 25 Kwon et al 16 2021 South Korea RC 49 0 19 Pre-XDR/XDR 28 DLM+LZD+CFZ+MEM/CLV+CYC 6 23 2 1 Shi et al 17 2021 China …”

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China

“…BDQ is an ATP synthase inhibitor and a novel agent recommended by the WHO for the treatment of MDR-TB [16]. Adding BDQ to standard treatment regimens for MDR-TB has been shown to improve the long-term survival of patients, reduce the time for sputum culture conversion, and increase the proportion of patients with consecutive negative culture results [17][18][19]. Given that patients with refractory RR/MDR/XDR-TB have few treatment options, BDQ might represent a useful choice for this population.…”

Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

“…Bedaquiline is an ATP synthase inhibitor and a novel agent recommended by the WHO for the treatment of MDR-TB [15]. Adding bedaquiline to standard treatment regimens for MDR-TB has been shown to improve the long-term survival of patients, reduce the time for sputum culture conversion, and increase the proportion of patients with consecutive negative culture results [16][17][18]. Given that patients with refractory RR/MDR-TB have few treatment options, bedaquiline might represent a useful choice for this population.…”