False equivalence of four‐month and six‐month ATT regimen: a case of comparing apples and oranges

We read with interest the article by Velayutham and colleagues, reporting on shorter regimens for newly diagnosed pulmonary tuberculosis [1]. Shortening the duration of tuberculosis treatment is an unmet research need [2]. In this regard, the trial by Velayutham et al. is commendable. Nevertheless, it has certain limitations. While the authors claim that the regimen has a high cure rate and acceptable recurrence rate, we have two main concerns regarding the applicability of this trial. First, the control regimen was the older thrice-weekly regimen. The intermittent regimen has a higher treatment failure, recurrence rate and acquired drug resistance. In a meta-analysis of 27 studies, the pooled relapse rate (95% CI) with the intermittent regimen was 7% (3–11%), with the daily regimen, 1% (0–3%) [3]. Thus, the current trial’s control regimen is clearly inferior to the existing standard of care and had a relapse rate of 4.5%. In this trial, the intermittent regimens, M4-I and M4-IE, had higher relapse rates of 8.7% and 6.4%, respectively, and were inferior to the daily dosing regimen (M4). The authors should have used the daily 6-month regimen, with an expected relapse rate of 1%, as the control arm. Further, moxifloxacin is a crucial component of the drug-resistant tuberculosis (DR-TB) regimen (class A drug), and its inappropriate use may lead to an increase in fluoroquinolone (FQ) resistance. Notably, FQ resistance is a pertinent issue in India, and the national drug resistance survey reports 22% resistance to FQ in subjects with MDR [4]. Even the current study noted a 3–7% resistance to ofloxacin in the various study groups comprising of treatment-naïve sputum-positive pulmonary tuberculosis patients. Hence, we believe that authors’ data do not support the use of a moxifloxacin-based 4-month regimen for treating sputum-positive pulmonary tuberculosis in India.