Similar Safety and Efficacy for Rifampin vs Isoniazid in Children, Adolescents

For children younger than 18 years, 4 months of rifampin to treat latent Mycobacterium tuberculosis had similar rates of safety and efficacy and higher rates of adherence compared with 9 months of isoniazid, according to data published in the New England Journal of Medicine.

A multicenter, open-label (ClinicalTrials.gov identifier: NCT00170209) randomized trial assigned participants with latent M tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. A total of 829 randomized participants were included in the intent-to-treat analysis. In the rifampin group (n=422), 85.3% of participants completed the therapy protocol compared with 76.4% of the isoniazid group; the adjusted difference in the rates of treatment completion was 13.4 percentage points (95% CI, 7.5-19.3). 

No significant differences in rates of adverse events were reported, and less than a combined 5% of participants across both groups experienced grade 1 or 2 adverse events that were deemed to be possibly related to the drug trial. Active tuberculosis was diagnosed in 2 individuals in the isoniazid group during the 542 person-years of follow-up, including 1 case of isoniazid resistance compared with 0 cases in rifampin group during a 562 person-year follow-up (rate difference, −0.37 cases per 100 person-years; 95% CI, −0.88 to 0.14).

The trial benefited from the randomized design and complete follow-up on 98% of participants. The main limitation was the open-label design, which can introduce biases in ascertainment of completion or adverse events. However, measures to reduce these biases, such as the implementation of blinded, independent third-party adjudication of all adverse events and active cases. According to investigators, for participants with latent tuberculosis, the 4-month rifampin therapy option has better completion rates than isoniazid while having similar safety and efficacy profiles. “Rifampin has the advantage of being a single-drug regimen with existing palatable formulations for children.”

Reference

Diallo T, Adjobimey M, Ruslami R, et al. Safety and side effects of rifampin versus isoniazid in children. N Engl J Med. 2018;379:454-463.