From the Journals

Better adherence, shorter course with rifampin for tuberculosis



Four months of rifampin is effective in prevention of active tuberculosis, with significantly higher adherence rates versus 9 months of isoniazid in adults and children, a pair of recent studies suggest.

a strain of tuberculosis is shown iLexx/Thinkstock

In one randomized, open-label trial that included adults with latent Mycobacterium tuberculosis infection, the 4-month rifampin regimen was not inferior to the 9-month isoniazid regimen in preventing active tuberculosis, had better safety, and had a rate of treatment completion 15.1 percentage points higher than the comparator.

“This trial adds to the mounting evidence of benefits of rifamycin-containing regimens of 3 or 4 months’ duration,” investigators reported in the New England Journal of Medicine.

Similarly, in an open-label study in children with latent M. tuberculosis infection, the shorter rifampin regimen had comparable efficacy and safety, according to investigators, along with a rate of treatment completion 13.4 percentage points higher than the longer isoniazid regimen.

“Rifampin has the advantage of being a single-drug regimen with existing palatable formulations for children,” reported authors of this companion study, also published in the journal.

Treatment challenges

Treating latent tuberculosis infection is central to the World Health Organization End TB Strategy and other tuberculosis elimination plans. An estimated 1.7 billion individuals, or about one-quarter of the global population, harbor latent tuberculosis infection, according to one recent estimate.

The WHO recommends treatment of latent tuberculosis infection, as well as for children under 5 years of age who are household contacts of individuals with tuberculosis. The recommended treatment is 6 or 9 months of isoniazid, with the longer duration being associated with better efficacy, previous studies have shown.

However, isoniazid treatment has been associated with low rates of regimen completion because of the hepatotoxic effects, according to authors of the current studies comparing isoniazid to rifampin.

The 4-month daily rifampin regimen has been associated with superior treatment adherence rates and fewer hepatotoxic effects, compared with the 9-month isoniazid regimen in previous observational studies. Moreover, an earlier randomized trial including 679 men in Hong Kong demonstrated that 3 months of rifampin was superior to placebo and comparable to 6 months of isoniazid as tuberculosis prophylaxis.

Rifampin: Latest data

The adult trial just published in the New England Journal of Medicine demonstrates the efficacy and real-world effectiveness of the 4-month rifampin regimen versus the 9-month isoniazid regimen for prevention of active tuberculosis, according to lead author Dick Menzies, MD, of the Montreal Chest Institute at McGill University Health Centre.

The 4-month rifampin regimen is a “fundamental game-changer in TB prevention” based on its comparable efficacy is adults, along with improved safety and acceptability, Dr. Menzies said in a recent press release.

Dr. Menzies and his colleagues reported on 6,063 adults (aged 18 years or older) randomized to the 4-month rifampin or 9-month isoniazid regimen at trial sites in Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea.

Treatment was completed by 78.8% of individuals in the rifampin arm, compared with 63.2% of patients in the isoniazid arm, for a difference of 15.1 percentage points (95% confidence interval, 12.7-17.4; P less than .001), the researchers reported.

Rifampin was not inferior to isoniazid in preventing tuberculosis, according to the report. In the per-protocol analysis, there were a total of five confirmed or clinically diagnosed cases of active tuberculosis in each of the trial arms. All active cases were treated successfully, including two cases that had demonstrated drug resistance, investigators added.

The rifampin group had consistently lower rates of grade 3-grade 5 adverse events, particularly hepatotoxic events, versus the isoniazid group, according to analyses outlined in the report.

“We believe this 4-month rifampin treatment should replace the 9 months on isoniazid for most people who need therapy for latent tuberculosis,” said Dr. Menzies, a respirologist with the Montreal Chest Institute and a professor of medicine, epidemiology and biostatistics at McGill University, also in Montreal.


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