August 02, 2018
2 min read

4 months of rifampin noninferior to 9 months of isoniazid for latent TB

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Researchers reported in The New England Journal of Medicine that 4 months of rifampin was noninferior to 9 months of isoniazid for the treatment of adults with latent tuberculosis. The shorter regimen was also associated with higher rates of treatment completion and better safety.

However, the researchers also noted that the 4-month regimen was not superior to the 9-month regimen.

“Many authorities, including WHO, recommend the treatment of latent tuberculosis infection with isoniazid for 6 or 9 months, with the longer duration showing evidence of greater protective efficiency,” Dick Menzies, MD, of the respiratory epidemiology and clinical research unit at McGill University, and colleagues wrote in the study. “However, the benefit of treatment with isoniazid is substantially reduced because of poor rates of regimen completion and because of hepatotoxic events.”

This information, with the added knowledge from previous observational studies of superior regimen completion and lower rates of hepatotoxic events with a 4-month regimen of daily rifampin, led the team of researchers to compare results of the two treatment options to see which was more effective when completed properly.

In an open-label trial conducted in nine countries, researchers randomly assigned approximately 6,800 adults with latent TB infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid to prevent active TB within 28 months.

Among the 3,443 patients in the rifampin group, 78.8% completed treatment, according to the study. Confirmed active TB developed in four participants, whereas four others developed clinically diagnosed active TB during 7,732 person-years of follow-up.

Only 63.2% of the 3,416 participants in the isoniazid group completed treatment. Confirmed active TB developed in four patients, and clinically diagnosed active TB developed in five patients during 7,652 person-years of follow-up.

The differences in rates were less than 0.01 case per 100 person-years (95% CI, –0.14 to 0.16) for confirmed active TB and less than 0.01 case per 100 person-years (95% CI, –0.23 to 0.22) for confirmed or clinically diagnosed TB, the researchers said.

The difference in the treatment completion rates was 15.1 percentage points, the researchers noted. The differences in rates of adverse events of grade 3 to 5 occurring within 146 days were –1.1 percentage points for all events and –1.2 percentage points for hepatotoxic events.

“The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety,” Menzies and colleagues concluded in the study.

Another study published in The New England Journal of Medicine involving participants aged younger than 18 years yielded similar results. Researchers in the study concluded that although 4 months of treatment with rifampin has comparable safety and efficacy as 9 months of isoniazid for the treatment of latent TB infection in children, adherence to treatment was greater among those who were administered rifampin. – by Caitlyn Stulpin


Diallo T, et al. New Engl J Med. 2018;doi:10.1056/NEJMoa1714284.

Menzies D, et al. New Engl J Med. 2018;doi:10.1056/NEJMoa1714283.

Disclosures: The authors report no relevant financial disclosures.