Four Months of Rifampicin May Be Best Option for Latent TB

By Reuters Staff

January 10, 2020

NEW YORK (Reuters Health) - Four months of daily rifampicin is "short, safe, and effective" and is likely the best way to achieve the ambitious goal set forth by the World Health Organization (WHO) to treat 30 million patients for latent tuberculosis infection by 2022, TB experts say in Lancet Infectious Diseases.

About one quarter of the world's population has latent TB infection. Daily isoniazid therapy is the most common treatment regimen used globally for latent TB but side effects are an "important problem limiting treatment," Dr. Jonathan Campbell from the McGill International TB Centre in Montreal and colleagues note in their report.

Across randomized trials and observational studies, compared with isoniazid, four months of daily rifampicin has "consistently" shown better completion rates, lower toxicity, and similar effectiveness, they point out.

Dr. Campbell and colleagues did a detailed safety analysis of four months of daily rifampicin compared with nine months of daily isoniazid for treatment of latent TB infection by combining data from phase 2 and phase 3 open-label, randomized controlled trials.

Four months rifampicin had about half the adverse events of nine months of daily isoniazid; 2.7% of participants receiving isoniazid suffered grade 1-2 rash or any grade 3-5 adverse events, compared with 1.5% of those receiving rifampicin (risk difference -1.2%).

Hepatotoxicity has been a major concern with isoniazid treatment for people aged 65 years and older.

"Importantly," say the researchers, in this age group, none of the 130 individuals taking rifampicin had grade 3-4 hepatotoxicity, compared with seven (6%) with hepatotoxicity among 127 receiving isoniazid.

Fear of generating rifampicin resistance through monotherapy of undetected active TB disease is one possible barrier to uptake of four months of daily rifampicin, the authors note. However, they say there is "good evidence that before initiating therapy, ruling out active tuberculosis using a combination of tuberculosis symptom screening, physical examination, chest radiography, and spontaneous sputum collection is adequate to protect against this risk."

"Of the currently available regimens for latent tuberculosis infection, we believe that rifampicin is the optimal choice on the basis of safety," they conclude.

The authors of a comment published with this analysis say it provides "important new safety data."

Dr. Simon Tiberi from Queen Mary University of London, UK and Dr. Giovanni Battista Migliori, from Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy, say rifampicin monotherapy "could make a difference to patient care while we await newer, shorter regimens for latent tuberculosis infection. The next generation of treatments might be better tolerated and easier to adhere to, allowing the management of more patient."

"It is essential," they conclude, "that the global tuberculosis community do active drug-safety monitoring and management as per WHO recommendations, so that we have better information regarding the tolerability and safety of newer agents and regimens."

The study was funded by the Canadian Institutes of Health Research. The study authors and comment authors have no relevant conflicts of interest.

SOURCE: and Lancet Infectious Diseases, online December 19, 2019.