Adverse events associated with treatment of latent tuberculosis in the general population

Guidelines recommend treatment of latent tuberculosis in patients at increased risk for active tuberculosis. Studies investigating the association of therapy with serious adverse events have not included the entire treated population nor accounted for comorbidities or occurrence of similar events in the untreated general population. Our objective was to estimate the risk of adverse events requiring hospital admission that were associated with therapy for latent tuberculosis infection in the general population.

Using administrative health data from the province of Quebec, we created a historical cohort of all residents dispensed therapy for latent tuberculosis between 1998 and 2003. Each patient was matched on age, sex and postal region with two untreated residents. The observation period was 18 months (from 6 months before to 12 months after initiation of therapy). The primary outcome was hospital admission for therapy-associated adverse events.

During the period of observation, therapy for latent tuberculosis was dispensed to 9145 residents, of whom 95% started isoniazid and 5% started rifampin. Pretreatment comorbid illness was significantly more common among patients receiving such therapy compared with the matched untreated cohort. Of all patients dispensed therapy, 45 (0.5%) were admitted to hospital for a hepatic event compared with 15 (0.1%) of the untreated patients. For people over age 65 years, the odds of hospital admission for a hepatic event among patients treated for latent tuberculosis infection was significantly greater than among matched untreated people after adjustment for comorbidities (odds ratio [OR] 6.4, 95% CI 2.2-18.3). Excluding patients with comorbid illness, there were two excess admissions to hospital for hepatic events per 100 patients initiating therapy compared with the rate among untreated people over 65 years (95% CI 0.1-3.87).

The risk of adverse events requiring hospital admission increased significantly among patients over 65 years receiving treatment for latent tuberculosis infection. The decision to treat latent tuberculosis infection in elderly patients should be made after careful consideration of risks and benefits.