Although numerous regimens are effective for preventing active tuberculosis in patients with latent disease, those containing rifamycin are shorter and may be preferable for some patients, researchers say.
“Reassuringly, particularly in the light of past drug shortages, our analysis suggests that several currently recommended regimens are efficacious, including different lengths of isoniazid monotherapy and rifamycin-containing regimens,” said Dr. Helen R. Stagg from University College London.
“This therefore shifts clinical decision-making in the choice of regimens to adverse event profiles, interactions with concomitant medications, factors influencing patient adherence, and regimen cost,” she told Reuters Health by email.
Dr. Stagg and colleagues undertook a network meta-analysis of 53 trials to assess the benefits and harms of 15 regimens aimed at preventing active tuberculosis in patients with latent infection.
The regimens included isoniazid (INH) only, rifampicin (RMP), RMP-INH, RMP-INH-pyrazinamide (PZA), RMP-PZA, INH-rifapentine (RPT), and INH-rifabutin (RFB).
The RFB-INH regimens ranked highest in efficacy, but regimens using RMP for three to four months or RMP-INH for three to four months were also particularly efficacious, the researchers report in the Annals of Internal Medicine, online August 12.
INH regimens of varying lengths had overlapping credible intervals, but efficacy was highest for those lasting 12 months or longer.
Hepatotoxicity appeared to be lower with RMP alone, RMP-INH, and RPT-INH than with INH alone, whereas regimens containing PZA had higher toxicity than six months of INH or 12 weeks of RPT-INH.
RMP-PZA regimens had the highest risk for gastrointestinal adverse effects, and RMP regimens had the highest risk for central nervous system adverse effects.
“Comparison of different latent tuberculosis treatment regimens showed that therapies containing rifamycin for 3 months or more were efficacious at preventing active tuberculosis, potentially more so than isoniazid alone,” the researchers conclude. “Regimens containing rifamycin may be effective alternatives to isoniazid monotherapy.”
“There is clearly a need for shorter, less toxic regimens for latent tuberculosis treatment,” Dr. Stagg said. “More clinical trials are required to provide the evidence for such regimens. Additionally, better evidence is needed for treatment of latent infections in individuals exposed to people with drug-resistant tuberculosis.”
“Finally,” she added, “there is currently very little knowledge on good predictors for progression from latent tuberculosis infection to active disease — these will be a vital tool for future tuberculosis control, when incorporated into cheap, easy-to-use, clinical tests.”