Shorter Course of Rifampin Safer & More Effective Than Isoniazid in Those with Latent TB


New research suggests 4 months of rifampin produced higher rates of adherence than 9 months of isoniazid in individuals with latent tuberculosis.

The treatment of latent tuberculosis is critical to prevent the development of tuberculosis disease. According to the World Health Organization (WHO) there were an estimated 10.4 million cases of TB reported worldwide in 2016. Furthermore, the Centers for Disease Control and Prevention (CDC) reports the highest numbers of TB cases are seen in children younger than 5 years of age and adolescents older than 10 years of age.

Now, the way the disease is treated might change in light of new research coming in from investigators at the Research-Institute of the McGill University Health Centre, who have found that treatment with just 4 months of rifampin had similar rates of safety and efficacy but a better rare of adherence when compared with 9 months of isoniazid in children and adults.

Isoniazid is the current standard of treatment for children with latent tuberculosis. Despite the seriousness of TB infection, isoniazid has been associated with poor adherence and toxic effects which have affected the effectiveness of the drug. Rifampin, a treatment that has been available for adults with latent TB, has been shown to be safer and to have higher compliance rates, according to the investigators.

In a multicenter, open-label trial, 844 children under the age of 18 years who had latent Mycobacterium tuberculosis were randomly assigned to receive either 4 months of rifampin or 9 months of isoniazid; of those who underwent randomization, 829 children were eligible for inclusion in the modified intention-to-treat analysis. Children assigned to the isoniazid group received 10 mg to 15 mg of the drug per kilogram of body weight per day, while children in the rifampin group received 10 mg to 20 mg of the drug per kilogram per day. The drugs were administered by the study participants or their caretakers.

At each visit, pills were counted by providers to determine if the doses were being administered regularly. Per-protocol treatment completion was defined by study authors as the receipt of at least 80% of doses during a specified period of time. Results indicate that 360 of the 422 children (85.3%) in the rifampin group completed per-protocol treatment compared with 311 of the 407 children (76.4%) who were in the isoniazid group (95% confidence interval [CI] 7.5 to 19.3.).

According to the data published in the New England Journal of Medicine, there were no significant differences in the rates of adverse events, with fewer than 5% of children reporting adverse events potentially related to a trial drug. Active TB was diagnosed in 2 children in the isoniazid group during 542 person-years of follow up, including 1 case with resistance to the drug; no diagnoses of active TB occurred in the rifampin group during 562 person-years follow up (95% CI, −0.88 to 0.14). This trial was part of a larger one that involved both adults and children.

In the study with adults aged 18 years and older, the investigators assigned 6859 participants to receive either 4-months of rifampin or a 9-month regimen of isoniazid. Investigators found that 2382 or 78.8% of participants in the rifampin group completed per-protocol treatment, compared with 1890 or 63.2% of the isoniazid group (95% CI 12.7-17.4).

Furthermore, the investigators found that of the 3443 patients in the rifampin group, 8 developed active TB during 7732 person-years of follow up. In the isoniazid group, 9 participants developed active TB among 3416 participants in 7652 years of follow up. Grade 3-5 adverse events were reported in 24 participants in the rifampin group, which was lower than the 73 reported in the isoniazid group.

In the adult study, the rifampin group had better rates of completion and better efficacy, demonstrating non-inferiority to the isoniazid group.

"This 4-month therapy is a fundamental game-changer in TB prevention," said Dick Menzies, MD, professor of medicine, epidemiology and biostatistics at McGill University in a recent statement. "The 4-month treatment was as effective in preventing TB, safer and more acceptable. We believe this 4-month rifampin treatment should replace the 9 months on INH for most people who need therapy for latent TB."

The studies were conducted in 9 different countries, Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea. Investigators are hopeful that the findings will have an impact on global practices for addressing the impact of TB.

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