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

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.