Short medication regimen noninferior to long regimen for rifampin-resistant TB


Background: Multidrug-resistant TB is more difficult to treat than is drug-susceptible TB. The 2011 World Health Organization (WHO) recommendations for the treatment of multidrug-resistant TB, based on very-low-quality and conditional evidence, consists of an intensive treatment phase of 8 months and total treatment duration of 20 months. Although cohort studies have shown promising cure rates among patients with multidrug-resistant TB who received existing drugs in regimens shorter than that recommended by the WHO, data from phase 3 randomized trials were lacking.

Study design: Randomized phase 3 noninferior trial.

Setting: Multisite, international; countries were selected based on background disease burden of TB, multidrug-resistant TB, and TB-HIV coinfection (Ethiopia, Mongolia, South Africa, Vietnam).

Synopsis: 424 patients were randomized to the short and long medication regimen groups with 369 included in the modified intention-to-treat analysis and 310 included in the final per protocol efficacy analysis. The short regimen included IV moxifloxacin, clofazimine, ethambutol, and pyrazinamide administered over a 40-week period, supplemented by kanamycin, isoniazid, and prothionamide in the first 16 weeks, compared with 8 months of intense treatment and total 20 months of treatment in the long regimen. At 132 weeks after randomization, cultures were negative for Mycobacterium tuberculosis in more than 78 % patients in both long- and short-regimen group. Unfavorable bacteriologic outcome (10.6%), cardiac conduction defects (9.9%), and hepatobiliary problems (8.9%) were more common in the short-regimen group whereas patients in long-regimen group were lost to follow-up more frequently (2.4%) and had more metabolic disorders (7.1%). More deaths were reported in the short-regimen group, especially in those with HIV coinfections (17.5%). Although the results of this trial are encouraging, further studies will be needed to find a short, simple regimen for multidrug-­resistant tuberculosis with improved safety outcomes.

Bottom line: Short medication regimen (9-11 months) is noninferior to the traditional WHO-­recommended long regimen (20 months) for treating rifampin-resistant tuberculosis.

Citation: Nunn AJ et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019 Mar 28; 380:1201-13.

Dr. Kamath is an assistant professor of medicine at Duke University.

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