Early discontinuation of ethambutol in pulmonary tuberculosis treatment based on results of the GenoType MTBDR plus assay: A prospective, multicenter, non-inferiority randomized trial in South Korea

Kyung-Wook Jo; Mihye Kim; Ye-Jee Kim; Hyun-Kyung Lee; Hyun Kuk Kim; Doosoo Jeon; Jiwon Lyu; Hye Kyeong Park; Jeongha Mok; Ju Sang Kim; Eun Young Heo; Sang Bong Choi; Jae-Joon Yim; Tae Sun Shim

doi:10.1128/AAC.00980-19

Early discontinuation of ethambutol in pulmonary tuberculosis treatment based on results of the GenoType MTBDR plus assay: A prospective, multicenter, non-inferiority randomized trial in South Korea

Antimicrob Agents Chemother. 2019 Sep 19;63(12):e00980-19. doi: 10.1128/AAC.00980-19. Epub 2019 Sep 16.

Authors

Kyung-Wook Jo¹, Mihye Kim², Ye-Jee Kim³, Hyun-Kyung Lee⁴, Hyun Kuk Kim⁵, Doosoo Jeon⁶, Jiwon Lyu⁷, Hye Kyeong Park⁸, Jeongha Mok⁹, Ju Sang Kim¹⁰, Eun Young Heo¹¹, Sang Bong Choi¹², Jae-Joon Yim¹³, Tae Sun Shim¹⁴

Affiliations

¹ Division of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
² Pulmonary, Allergy and Critical Care Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
³ Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, South Korea.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea.
⁵ Department of Pulmonary and Critical Care Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.
⁶ Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea.
⁷ Division of Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of medicine, Ilsan, South Korea.
⁹ Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea.
¹⁰ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Incheon, South Korea.
¹¹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.
¹² Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
¹³ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
¹⁴ Division of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea shimts@amc.seoul.kr.

Abstract

No studies have investigated whether discontinuation of ethambutol (EMB) based on the susceptibility to isoniazid and rifampin as determined by the GenoType MTBDRplus assay would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of intensive phase treatment based on the result of MTBDRplus assay in patients with pulmonary tuberculosis (PTB). This prospective, multicenter non-inferiority randomized trial was conducted at 12 referral centers in South Korea in drug-susceptible PTB patients who initiated the standard four-drug regimen for PTB. Based on the results of the assay, EMB was discontinued in the MTBDRplus group after the confirmation that M. tuberculosis isolate was susceptible to isoniazid and rifampin. The timepoint for EMB discontinuation in the Guideline group was determined using the results of the phenotypic drug susceptibility test based on the Korean National TB Guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Of 600 randomized patients, the treatment outcome analysis was performed for 493 patients (MTBDRplus group, 244; Guideline group, 249). Treatment success rates were 93.9% (229/224) in the MTBDRplus group and 93.6% (233/249) in the Guideline group and did not differ between groups; relative risk 1.00 (95% CI 0.95-1.06). The 1-year recurrence rate between the two groups (0.9% vs. 0.5%, respectively) and differences in adverse drug reactions did not differ between groups. In conclusion, early discontinuation of EMB based on the results of the MTBDRplus assay did not affect the treatment outcomes in PTB.