Shorter Treatment for Nonsevere Tuberculosis

Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen. The trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India with under 16 years of age were randomly assigned to 16 weeks or 24 weeks of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by WHO.

The primary efficacy outcome was unfavorable status by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment.The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.

Overall, 1204 children underwent randomization, the median age of the participants was 3.5 years. 52% were male, 11% had HIV and 14% had bacteriologically confirmed tuberculosis .A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group.The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline,A cost-effectiveness analysis showed that at 72 weeks, participants who had been treated for 4 months had similar health outcomes as those who had been treated for 6 months but with lower health care costs.

Thus, Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2104535