PURLs

A better approach to preventing active TB?

J Fam Pract. 2020 January;69(1):37-38

References

1. 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.

2. Stewart RJ, Tsang CA, Pratt RH, et al. Tuberculosis — United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67:317-323.

3. Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modeling. PLoS Med. 2016;13:e1002152.

4. Lönnroth K, Migliori GB, Abubakar I, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J. 2015;45:928-952.

5. Uplekar M, Weil D, Lonnroth K, et al. WHO’s new end TB strategy. Lancet. 2015;385:1799-1801.

6. Centers for Disease Control and Prevention. Treatment regimens for latent TB infection (LTBI). Last reviewed April 5, 2016. https://www.cdc.gov/tb/topic/treatment/ltbi.htm. Accessed January 15, 2020.

7. World Health Organization. Latent TB infection: updated and consolidated guidelines for programmatic management. 2018. Publication no. WHO/CDS/TB/2018.4. https://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/. Accessed January 15, 2020.

8. Borisov AS, Bamrah Morris S, Njie GJ, et al. Update of recommendations for use of once-weekly isoniazid-rifapentine regimen to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2018;67:723-726.

9. Macaraig MM, Jalees M, Lam C, et al. Improved treatment completion with shorter treatment regimens for latent tuberculous infection. Int J Tuber Lung Dis. 2018;22:1344-1349. 10. Sharma SK, Sharma A, Kadhiravan T, et al. Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. Cochrane Database Syst Rev. 2013;(7):CD007545.

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.

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