Treatment of latent tuberculosis: efficacy vs effectiveness

I've blogged before about the poor options we have for treating latent tuberculosis. The standard regimen, 9 months of isoniazid (INH), is too long and too toxic for the treatment of tuberculosis that is not active. For patients that aren't immunosuppressed and not recent skin test converters, the risk for developing active tuberculosis is only about 5%. Though the data for efficacy are not as robust, the 4-month daily rifampin regimen is much easier and better tolerated, and I have become more comfortable with this regimen. Because of the referral nature of my practice, the patients referred to me for evaluation of latent tuberculosis often have elevated liver enzymes at the outset or may not want to wait 9 months to complete the standard regimen before starting a therapy they feel is important (e.g., TNF-alpha inhibitors or other immunosuppressants).

A new study reported in this month's Chest examines completion rates of latent TB treatment courses. The investigators found that less than half of persons started on a treatment course actually finish it. About 45% complete a 9-month course of INH, 55% complete a 6-month course of INH, and nearly 65% complete the 4-month rifampin regimen. This leads me to wonder: even if 9 months of INH were ultimately proven to be more efficacious, perhaps 4-months of rifampin is more effective. Efficacy refers to how well a therapy works under ideal conditions (i.e., you take all the doses as prescribed), whereas effectiveness refers to how well a therapy works under real-world conditions (i.e., how well does the drug work when compliance is factored in). Given the toxicities of INH and the longer duration of treatment, coupled with the results of this survey, it's not far-fetched to conclude that what is considered our most efficacious regimen for latent tuberculosis may be our least effective.