A 4-month regimen of rifampin was not inferior to 9 months of treatment with isoniazid in preventing active tuberculosis [TB], but neither was the rifampin regimen superior to isoniazid, according to findings published in the New England Journal of Medicine.  Of note, patients treated with rifampin had a higher rate of treatment completion and the incidence of grade 3 to 5 adverse events was significantly lower.

Treatment with isoniazid for 6 or 9 months has been recommended for treating latent TB infection, but the benefit is often substantially reduced due to poor rates of regimen completion and associated hepatotoxic effects. In an open-label, randomized, controlled international trial conducted in 9 countries, 6012 adults with latent TB infection were assigned to either a 4-month regimen of rifampin or a 9-month regimen of isoniazid with the goal of preventing active TB within a 28-month period.

In the rifampin group (n=3443), there were 4 confirmed active cases of TB and clinically diagnosed active TB developed in 4 patients vs 4 and 5 patients, respectively, in the isoniazid (n= 3416) group. The difference in rate (rifampin minus isoniazid) was less than .01 cases per 100 person-years (95% CI, -14 to .16) for confirmed active TB and less than .01/100 (95% CI, -.23 to .22) for confirmed or clinically diagnosed TB. The rate of completion was higher in the rifampin vs the isoniazid arm by 15.1% (95% CI, 12.7 to 17.4). The difference in the rate of grade 3 to 5 adverse events occurring within 146 days was -1.1% (95% CI, -1.9 to -.4) for all events. The most common serious adverse event was drug-induced hepatitis and was significantly less frequent in the rifampin group than the isoniazid group.

With the strengths of a large, randomized sample and only 7.9% of participants lost to follow-up, investigators concluded that, “This trial adds to the mounting evidence of benefits of rifamycin-containing regimens of 3 or 4 months’ duration.”

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Menzies D, Adjobimey M, Ruslami R, et al. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. N Engl J Med. 2018g;379(5):440-453.