A better approach to preventing active TB?
Nine months of isoniazid prevents active TB in those with latent disease. But is there a shorter, less toxic option?
PRACTICE CHANGER
Use 4 months of rifampin instead of 9 months of isoniazid to treat adults with latent tuberculosis; rifampin is associated with fewer adverse events and higher completion rates.
STRENGTH OF RECOMMENDATION
A: Based on a randomized controlled trial and a previous Cochrane review.
Menzies D, Adjobimey M, Ruslami R, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. N Engl J Med. 2018;379:440-453.
Results. Overall, rates of active TB were low with 9 cases in the isoniazid group and 8 in the rifampin group. In the intention-to-treat analysis, the rate difference for confirmed active TB was < 0.01 cases per 100 person-years (95% CI; −0.14 to 0.16). This met the prespecified noninferiority endpoint, but did not show superiority. A total of 79% of patients treated with rifampin vs 63% treated with isoniazid completed their respective medication courses (difference of 15.1 percentage points; 95% CI, 12.7-17.4; P < .001). Compared with patients in the isoniazid group, those taking rifampin had fewer adverse events, leading to discontinuation (5.6% vs 2.8%).
WHAT’S NEW?
First high-quality study to show that less is more
This is the first large, high-quality study to show that a shorter (4 month) rifampin-based regimen is not inferior to a longer (9 months) isoniazid-based regimen for the treatment of LTBI, and that rifampin is associated with improved adherence and fewer adverse events.
CAVEATS
Low rate of active TB infection and potential bias
The current study had lower-than-anticipated rates of active TB infection, which made the study’s conclusions less compelling. This may have been because of a small number of patients with human immunodeficiency virus enrolled in the study and/or that even participants who discontinued treatment received a median of 3 months of partial treatment.
In addition, the study was an open-label RCT, subjecting it to potential bias. However, the diagnosis of active TB and attribution of adverse events were made by an independent, blinded review panel.
CHALLENGES TO IMPLEMENTATION
No challenges to speak of
We see no challenges to implementing this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
