Abstract
BackgroundWe conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI). While a previous review found newer, short-duration regimens to be effective, several included studies did not confirm LTBI, and analyses did not account for variable follow-up or assess completion.MethodsWe searched MEDLINE, Embase, CENTRAL, PubMed, and additional sources to identify RCTs in patients with confirmed LTBI that involved a regimen of interest and reported on efficacy or completion. Regimens of interest included isoniazid (INH) with rifapentine once weekly for 12 weeks (INH/RPT-3), 6 and 9 months of daily INH (INH-6; INH-9), 3–4 months daily INH plus rifampicin (INH/RFMP 3–4), and 4 months daily rifampicin alone (RFMP-4). NMAs were performed to compare regimens for both endpoints.ResultsSixteen RCTs (n = 44,149) and 14 RCTs (n = 44,128) were included in analyses of efficacy and completion. Studies were published between 1968 and 2015, and there was diversity in patient age and comorbidities. All regimens of interest except INH-9 showed significant benefits in preventing active TB compared to placebo. Comparisons between active regimens did not reveal significant differences. While definitions of regimen completion varied across studies, regimens of 3–4 months were associated with a greater likelihood of adequate completion.ConclusionsMost of the active regimens showed an ability to reduce the risk of active TB relative to no treatment, however important differences between active regimens were not found. Shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens. Regimens of 3–4 months duration are more likely to be completed than longer regimens.
Highlights
We conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI)
[3] Many retain a population of viable Mycobacterium tuberculosis bacilli that is sequestered by the immune system, a state which is termed latent tuberculosis infection (LTBI)
Priors used for between study variance in these analyses were chosen based on empirical estimates previously reported elsewhere [14], lognormal(μ = −3.23, σ2 = 1.882); as model fit was adequate for both endpoints and comparable to Random Effects (RE) vague fit based upon deviance information criteria, these results were chosen to be the basis for primary clinical interpretations
Summary
We conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI). [4] Clinically, LTBI is defined by a persistent immune response to M. tuberculosis antigens without evidence of active disease [2]. Immune response can be assessed by both tuberculin skin testing (TST) and the interferongamma release assay (IGRA) [2]. Those with LTBI are neither infectious nor symptomatic, but are estimated to have a 5–15% lifetime risk of developing active TB from reactivation of their infection [3]. A subsequent analysis focusing on the pediatric population within this trial found similar results [6]
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