SESSION TITLE: TB
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Sunday, October 27, 2013 at 03:00 PM - 04:00 PM
PURPOSE: A point of contention in treating latent tuberculosis (TB) is whether greater efficacy can be achieved with highly potent but toxic agents or less potent agents that are more tolerable and less likely to lead to noncompliance. Little is known about the correlation between drug compliance and clinically important outcomes like mortality and conversion to active TB. A meta-regression of all randomized controlled trials (RCT’s) involving latent TB was performed to determine if the rate of study withdrawal is associated with improved outcomes.
METHODS: 23 RCTs involving treatment of latent TB were identified. These studies included four regimens: Isoniazid (INH) for 6-12 months, INH/Rifamycin, Rifamycin/Pyrazinamide and Rifamycin alone. Withdrawals were defined as patients that left the study either because of adverse events, being “lost-to-follow-up”, noncompliance or physician determination. Additionally, patients that specifically prematurely withdrew from the study due to adverse events were identified as well. Multivariate meta-regression analysis, employing a random-effects model, was performed to evaluate whether either overall withdrawals or withdrawals due to adverse events may have influenced either risk of mortality or risk of conversion to active TB.
RESULTS: There was a highly statistically significant correlation between overall withdrawals and the risk of conversion to active TB (p=0.01). It was also evident, but to a lesser degree (p=0.05), in evaluating specifically the rate of the withdrawals due to adverse events. No correlation existed between mortality and either overall withdrawals or withdrawals due to adverse events.
CONCLUSIONS: A higher rate of withdrawals is suggestive of a drug regimen that is poorly tolerated or given over too long a period and is likely to lead to a higher risk of conversion to active TB. Importantly, this increased conversion risk includes only patients that remained in the given study. As a result, it likely underestimates the risk of conversion to active TB.
CLINICAL IMPLICATIONS: Compliancy of a treatment regimen for latent TB may be as important as potency in determining its efficacy.
DISCLOSURE: The following authors have nothing to disclose: Elie Donath, Bianca Sarmento, Jonathan Schroeder, David Ashkin
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