A FOUR-MONTH tuberculosis treatment regimen showed comparable efficacy and safety to standard six-month therapy in selected patients. Findings from the ESCAPE-TB2 randomized controlled trial, presented at IDWeek 2026, suggest that treatment duration could be reduced for adults with low-risk, drug-susceptible pulmonary tuberculosis (TB), without increasing recurrence.
Shorter Tuberculosis Treatment Compared With Standard Care
The three-year, prospective, multicenter trial enrolled 270 adults with low-risk, paucibacillary, drug-susceptible pulmonary TB. Low-risk disease was defined by sputum acid-fast smear results of 1+ or trace, unilateral involvement of no more than two lung lobes, or compatible histopathology with positive microbiological testing.
Participants were randomized to receive either four months of treatment, comprising two months of isoniazid, rifampin, ethambutol, and pyrazinamide followed by two months of isoniazid and rifampin, or the standard six-month regimen, with a four-month continuation phase.
The preliminary analysis included 167 randomized patients, with 84 assigned to the shorter regimen and 83 to standard treatment. Baseline characteristics were comparable, with a mean age of 67.6 years and 64.7% aged 65 years or older.
Comparable Safety and Sputum Conversion
Adverse event rates were nearly identical between the four-month and six-month groups, at 57.1% and 57.8%, respectively (p=0.93). Most adverse events were mild, with Grade 1 events accounting for 49.1% and Grade 2 events for 26.4%.
Treatment discontinuation due to adverse events occurred in 18.5% of patients receiving shorter therapy versus 11.2% receiving standard treatment, although the difference was not statistically significant (p=0.18).
Sputum smear and culture conversion rates were high in both groups at weeks 8, 16, and 24. At week 8, positive sputum cultures persisted in 3.1% of the four-month group and 5.4% of the six-month group.
No Tuberculosis Recurrence Observed
No tuberculosis relapse or recurrence was observed within 12 months after treatment, with tuberculosis disease-free survival reaching 100% among evaluable patients.
These preliminary findings support further evaluation of shortened therapy for carefully selected patients with drug-susceptible pulmonary TB. However, the results do not establish noninferiority, and the findings may not apply to patients with more extensive disease.
A shorter regimen could reduce treatment burden while preserving favorable outcomes, although longer-term follow-up remains important before broader implementation.
Reference
Lee SSJ et al. Efficacy and safety of a short-course, daily, 4-month regimen (2HREZ/2HR) vs standard 6-month regimen (2HREZ/4HR) for the treatment of drug-susceptible, low-risk, active pulmonary Tuberculosis: A multicenter, randomized controlled trial (ESCAPE-TB2). IDWeek, October 21–24, 2026.
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