Isoniazid and Rifampin for Persons with Radiographic Evidence of Previous Tuberculosis
abstract & commentary
Synopsis: Persons with a positive tuberculin skin test who have radiographic evidence of prior tuberculosis are at increased risk of subsequent development of active tuberculosis. This study compared the completion rates, adverse events, and cost-effectiveness of two regimens (isoniazid for 12 months vs isoniazid + rifampin for 4 months) for the treatment of latent tuberculosis infection. The study demonstrated similar completion rates and adverse events between the two regimens but showed a cost savings with the two-drug regimen.
Source: Jasmer RM, et al. Am J Respir Crit Care Med 2000; 162:1648-1652.
The american thoracic society (ats) and the Centers for Disease Control (CDC) guidelines recommend that patients with radiographic evidence of previous tuberculosis (TB) and a 5 mm PPD receive treatment for latent tuberculosis infection (LTBI).1 All patients with a PPD of more than 5 mm and radiographic evidence consistent with old TB evaluated at the San Francisco Tuberculosis Clinic from 1993-1996 were included in the study after active TB was ruled out. A total of 1022 patients were begun on treatment. Ninety-three percent of the patients were born outside of the United States with more than 75% from southeast Asia. Almost all (96%) patients seen from 1993-1994 were given isoniazid (INH) alone and all patients seen from 1995-1996 were given INH plus rifampin (RIF). Patients were evaluated monthly for adherence to therapy and possible side effects.
A total of 545 patients received INH alone and 477 received INH plus RIF. In the INH alone group, 435 of 545 (79.8%) completed 12 months, 19 of 545 (3.5%) completed 6-11 months, and 91 of 545 (16.7%) completed less than six months. In the INH plus RIF group, 399 of 477 (83.6%) completed four months, 34 of 477 (7.1%) completed 2-3 months, and 44 of 477 (9.2%) completed less than two months. In the INH group, 26 of 545 (4.8%) had adverse events and in the INH plus RIF group, 29 of 477 (6.1%) had adverse events. There was no significant difference between groups with respect to completion rates or adverse events.
The total cost of treatment with INH for 12 months was $594 and with INH plus RIF the cost was $592. Evaluating cost-effectiveness relative to no treatment for LTBI produced a savings of $728 per patient in the INH group and $864 per patient in the INH plus RIF group. Thus, the INH plus RIF strategy saved $136 per patient treated compared with the INH alone strategy. The INH plus RIF strategy was also superior when compared to a strategy of nine months of INH alone with a cost savings of $92 per patient.
Comment by David Ost, MD, & Suketu K. Shah, MD
INH was introduced in 1952 to treat active TB and by 1955, it was also used as prophylaxis to prevent active disease. Treatment of LTBI (previously referred to as prophylaxis) is still an important health concern. Current recommendations for treatment of LTBI include either INH for nine months or rifampin plus pyrazinamide for two months or rifampin alone for four months.
Although this study used a longer INH regimen and a different two-drug regimen than in the current ATS/CDC recommendations, they were chosen based upon literature at the time of the study.2 There was no significant difference in the development of active TB, adverse events, and completion rates between the two strategies in the study.
The shorter two-drug regimen was more cost effective than the INH alone group and the study also demonstrated a cost savings for either strategy compared to no treatment for LTBI. Jasmer and colleagues also compared the two-drug regimen to the current recommendation of only nine months of INH and still showed a cost savings for the two-drug regimen. INH-resistant TB was not factored into this study, which, if included, would increase the cost of treating the INH group because of treatment failures. The two-drug regimen would not have as many failures because rifampin alone has been shown to have efficacy against LTBI.3 Another advantage of the two-drug regimen vs. INH alone is if a patient actually had unrecognized active TB as opposed to LTBI there would be a lesser likelihood of developing resistance on the two-drug regimen.
Costs in this study were analyzed from the perspective of the health care system. The study does not include the patients’ opinions about the ease of a four-month vs. a 12-month regimen with clinic appointments. One would suspect that patients would favor a shorter regimen.
References
1. American Thoracic Society and Centers for Disease Control and Prevention. Am J Respir Crit Care Med 2000;161:S221-S247.
2. American Thoracic Society and Centers for Disease Control. Am J Respir Crit Care Med 1994;149: 1359-1374.
3. Hong Kong Chest Service. Am Rev Respir Dis 1992; 145:36-41.
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