Isoniazid Prophylaxis for TB: It's Time To Re-evaluate Our Thinking
ABSTRACT & COMMENTARY
Synopsis: This paper outlines the cost-effectiveness of monitored isoniazid prophylaxis for low-risk tuberculin reactors who are older than 35 years of age. The authors report that mortality rates and healthcare costs for this population were reduced. Although changes for individual patients were small, significant potential benefits were demonstrated for the U.S. population as a whole.
Source: Salpeter SR, et al. Ann Intern Med 1997;127:1051-1061.
Tuberculosis remains a significant public health problem throughout the world, including the United States. The preventive management of tuberculosis remains controversial, with studies supporting and disputing the use of isoniazid prophylaxis for tuberculin reactors in all age groups. Because of the risk of isoniazid hepatitic toxicity, the American Thoracic Society indicated, in their 1974 publication, that prophylaxis for tuberculin reactors be restricted to those under age 35 or to high-risk individuals over age 35 and that isoniazid treatment be withheld from patients with acute liver disease. Although subsequent clinical practice guidelines have suggested ongoing monitoring of liver function testing during isoniazid treatment to prevent hepatitis, the recommendations for patients over 35 have remained unchanged. High-risk tuberculin reactors include: 1) close contacts of patients with tuberculosis; 2) recent convertors or persons who have chest radiographs consistent with inactive or poorly treated tuberculosis; 3) alcoholics; and 4) intravenous drug users. This group often develops tuberculosis with rates as high as 5% annually.1
Salpeter et al used a Markov model to compare health and economic outcomes for either giving or withholding isoniazid prophylaxis for low-risk reactors, ages 35, 50, or 70. Additional analyses of secondary transmission of tuberculosis were performed. Outcome measures included survival at one year, number needed to treat, life expectancy, and cost per year of life gained. Results strongly favored the use of isoniazid prophylaxis for low-risk tuberculin reactors over 35 years of age. Compared to no prophylaxis, the administration of isoniazid with monitoring increased the likelihood of survival during the first year, during which the risk of isoniazid hepatitis would be greatest; and, during all subsequent years, it decreased the lifetime risk of death from tuberculosis. In all age groups, increased life expectancy was demonstrated. Medical expenditures in all age groups were also reduced, and the authors reported that applying isoniazid prophylaxis to older patients would avert more than 7000 deaths and save more than $400 million in healthcare resources. This would occur even if only one-fifth of low-risk tuberculin reactors were treated. Specifically, prophylaxis increased life expectancy by approximately five days for 35-year- olds and 50-year-olds and three days for 70-year-old patients. The greatest degree of healthcare saving occurred in the 35-year-olds ($101) compared to 70-year-olds, for whom there was a savings of only $11. Costs were reduced because of the savings incurred by prevention of active tuberculosis. If all low-risk patients over age 35 were treated in the United States, the savings could approach $2 billion. In their sensitivity analysis, the authors demonstrate that the rate of fatal isoniazid hepatitis would have to be 35 times greater than is currently estimated for the prophylaxis strategy not to be preferred.
COMMENT BY ALAN M. FEIN, MD
Currently, both the American Thoracic Society and the Center for Disease Control recommend that tuberculin reactors over age 35, who have no risk factors, not be treated with isoniazid. This includes foreign-born persons, medically underserved, low-income populations, and residents of long-term care facilities. However, significant controversy has been generated by this approach since the risk of isoniazid hepatitis was primarily from observation performed at a time when liver-function monitoring was not part of routine care. Salpeter et al report that the risk of fatal hepatitis is 0.001% and under 1% for all recent analyses. This is in contradistinction to report by Stead et al, in which 4.5% of elderly nursing home residents treated with isoniazid developed hepatitis.2 Using the Markov model and sensitivity analysis, the authors make a cogent case for improved morbidity and mortality, as well as reduced costs, for isoniazid treatment of low-risk tuberculin reactors of all ages. These benefits were enhanced even further when the effect of the individual patient's potential transmission of M. tuberculosis to contacts was included. Although it has been reported that practitioners failed to use isoniazid prophylaxis in up to two-thirds of eligible patients, this may be related to "fear" of isoniazid hepatitis. These investigators suggest that the benefits of isoniazid prophylaxis in all age groups outweigh the risk of death from hepatitis. In fact, the rate of fatal hepatitis would have to be at least 35 times greater than their base estimate for it to be reasonable to withhold isoniazid to low-risk reactors. This report should go a long way toward encouraging a re-evaluation of isoniazid prophylaxis policies. Perhaps, these complex guidelines can be simplified if we offer isoniazid to all tuberculin reactors regardless of age.
References
1. Centers for Disease Control. MMWR Morb Mortal Wkly Rep 1990;39 (NO. RR-8):1-12.
2. Stead WW, et al. Ann Intern Med 1987;107:843-845.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content. TESTING
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content