Early effectiveness and safety of bedaquiline containing regimen in treatment of multidrug-resistant and extensively drug-resistant tuberculosis: An one arm observational study of 24 weeks

doi:10.3969/j.issn.1000-6621.2021.05.014

Abstract

Abstract:

Objective To evaluate the early effectiveness and safety of bedaquiline containing regimen in the treatment of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Methods Patients were enrolled in Chengdu Public Health Clinical Medical Center from Mar. 2018 to Aug. 2019 and then were given bedaquiline containing anti-tuberculosis treatment. Fifty cases were enrolled, among which 8 (16.0%), 20 (40.0%), 22 (44.0%) patients were with multidrug-resistant, pre-extensively drug-resistant and extensively drug-resistant tuberculosis respectively. Within 24 weeks, Mycobacterium tuberculosis culture conversion rate and treatment outcome were analyzed to assess treatment effectiveness. Adverse events and QTcF were recorded to assess treatment safety. Results Forty-five (90.0%) cases completed follow-up at 24 weeks, 3 cases were lost, 2 cases died. 84.2% (32/38) of the patients with base-line sputum culture positive had achieved sputum culture conversion, the median time for culture conversion was 8 (4,16) weeks. 84.0% (42/50) of patients showed favorable outcomes. BMI <18.5 was an independent risk factor for treatment success (OR=0.070, 95%CI=0.005-0.922). A total of 221 adverse events occurred in 47 patients (94.0%, 47/50), and 5 severe adverse events occurred in 5 patients (including 2 deaths). The median QTcF value of 50 patients at baseline was 397.5 (385.0, 411.0) ms, which fluctuated between 417.0 (402.0, 440.0) ms (at 24 weeks) and 434.0 (403.0, 445.0) ms (at 8 weeks) after treatment (420.0 (406.0, 438.0) ms at 4 weeks, 420.0 (390.0, 440.0) ms at 12 weeks, 420.0 (400.0, 439.0) ms at 16 weeks, 418.0 (399.0, 440.0) ms at 20 weeks). There were statistically significant difference on QTcF value at each monitoring time compared with that at baseline (Z=-3.903, P<0.001, at 4 weeks; Z=-3.770, P<0.001, at 8 weeks; Z=-2.673, P=0.008, at 12 weeks; Z=-3.370, P=0.001, at 16 weeks; Z=-3.550, P<0.001, at 20 weeks; Z=-3.013, P=0.003, at 24 weeks, respectively). Six patients (12.0%, 6/50) permanently stopped using bedaquiline due to QTcF >500 ms. Conclusion Using bedaquiline containing anti-tuberculosis regimen could achieve high culture conversion rates in patients with MDR and XDR-TB, it was well tolerated too.

Key words: Extensively drug-resistant tuberculosis, Bedaquiline, Drug evaluation, Observational study

SHI Zheng-yu, WU Gui-hui, HUANG Tao, LIU Yu-hong, GAO Meng-qiu, CHEN Lei, LI Xi, YANG Ming, HE Wei, CHEN Yan, LU Xiao-li, GAO Jing-tao, LI Liang. Early effectiveness and safety of bedaquiline containing regimen in treatment of multidrug-resistant and extensively drug-resistant tuberculosis: An one arm observational study of 24 weeks[J]. Chinese Journal of Antituberculosis, 2021, 43(5): 487-494. doi: 10.3969/j.issn.1000-6621.2021.05.014

Figures/Tables 6

因素	β值	s $x ˉ$ 值	Wald χ²值	P值	OR值	95%CI值
性别(男性)	0.767	0.921	0.692	0.405	2.152	0.354~13.097
年龄(40~63岁)	-1.448	1.229	1.389	0.239	0.235	0.021~2.612
BMI(<18.5)	-2.661	1.316	4.089	0.043	0.070	0.005~0.922
耐药类型
MDR-TB	-	-	0.898	0.638	-	-
Pre-XDR-TB	1.293	1.387	0.869	0.351	3.644	0.240~55.219
XDR-TB	0.632	1.090	0.337	0.562	1.882	0.222~15.926
常量	3.544	2.383	2.212	0.137	34.609	-

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类别	例数	构成比(%)
性别
男	36	72.0
女	14	28.0
年龄组(岁)^a
18~39	33	66.0
40~59	15	30.0
60~63	2	4.0
BMI
<18.5	13	26.0
≥18.5	37	74.0
并发症
糖尿病	6	12.0
乙型肝炎	5	10.0
HIV感染	1	2.0
累及部位
单纯肺部	36	72.0
肺部+其他部位	14	28.0
累及肺叶
单个肺叶	11	22.0
多个肺叶	39	78.0
类别	例数	构成比(%)
肺部空洞
无	9	18.0
有	41	82.0
耐药类型
MDR-TB	8	16.0
Pre-XDR-TB	20	40.0
Pre-XDR-TB耐氟喹诺酮类药物	17	34.0
Pre-XDR-TB耐二线注射类药物	3	6.0
XDR-TB	22	44.0
基线结核分枝杆菌培养
阳性	38	76.0
阴性	12	24.0

因素	治疗成功(42例)		不良转归(8例)		χ²值	P值
因素	例数	构成比(%)	例数	构成比例^a	χ²值	P值
性别					0.050	0.823
男	31	73.8	5	5/8
女	11	26.2	3	3/8
年龄组(岁)^b					0.001	0.999
18~39	28	66.7	5	5/8
40~63	14	33.3	3	3/8
BMI					4.530	0.033
<18.5	8	19.0	5	5/8
≥18.5	34	81.0	3	3/8
耐药类型					-	0.217^c
MDR-TB	6	14.3	2	2/8
Pre-XDR-TB	19	45.2	1	1/8
XDR-TB	17	40.5	5	5/8

变量	赋值
自变量
性别	女=0;男=1
年龄	18~39岁=0;40~63岁=1
BMI	≥18.5=0;<18.5=1
耐药类型	MDR-TB=1;Pre-XDR-TB=2;XDR-TB=3
因变量
24周治疗转归	不良转归=0; 治疗成功=1

监测时间	QTcF [ms,M(Q₁,Q₃)]	Z值	P值^a
基线	397.5(385.0,411.0)	-	-
治疗4周	420.0(406.0,438.0)	-3.903	<0.001
治疗8周	434.0(403.0,445.0)	-3.770	<0.001
治疗12周	420.0(390.0,440.0)	-2.673	0.008
治疗16周	420.0(400.0,439.0)	-3.370	0.001
治疗20周	418.0(399.0,440.0)	-3.550	<0.001
治疗24周	417.0(402.0,440.0)	-3.013	0.003