title: Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses.
abstract: We 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.
  
  
  
  We 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.
  
  
  
  Sixteen 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.
  
  
  
  Most 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.
authors.affiliation: Department of Medicine, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pease
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. bhutton@ohri.ca.|Ottawa University School of Epidemiology, Public Health and Preventive Medicine, Ottawa, Canada. bhutton@ohri.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yazdi
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Dianna
authors.initials: D
authors.lastname: Wolfe
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Candyce
authors.initials: C
authors.lastname: Hamel
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Quach
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Becky
authors.initials: B
authors.lastname: Skidmore
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.|Ottawa University School of Epidemiology, Public Health and Preventive Medicine, Ottawa, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.affiliation: Department of Medicine, The Ottawa Hospital, Ottawa, Canada.|Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.|Ottawa University Faculty of Medicine, Ottawa, Canada.
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: Alvarez
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D055985:Latent Tuberculosis / Q000188:drug therapy*; D008297:Male; D012293:Rifampin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine
keywords: Latent tuberculosis infection; Network meta-analysis; Systematic review