title: Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies: a systematic review.
abstract: OBJECTIVE
  Patients receiving therapy for haematological malignancies have a higher risk of invasive fungal infections (IFIs). Antifungal prophylaxis is an effective strategy against IFIs, but relative effectiveness estimates across agents are inconclusive. A mixed treatment comparison (MTC) was conducted to estimate the relative effectiveness of all agents for a number of outcomes of interest.
  
  
  METHODS
  A systematic review was performed to collect evidence from randomized controlled trials (RCTs) on the risk of IFIs and on mortality after antifungal prophylaxis. The agents analysed were no prophylaxis/placebo, fluconazole, itraconazole, micafungin, caspofungin, liposomal amphotericin B and posaconazole. Meta-analyses and MTCs were used to synthesize the evidence. The primary outcome was the risk of proven or probable IFI. Secondary outcomes were risk of candidiasis/aspergillosis, risk of IFI mortality and risk of all-cause mortality.
  
  
  RESULTS
  Antifungal prophylaxis was more effective than no prophylaxis/placebo in reducing IFI risk. The IFI risk after voriconazole or posaconazole was lower than after fluconazole [relative risk (RR) 0.38, 95% CI 0.14-0.83 and RR 0.34, 95% CI 0.14-0.83] or itraconazole tablets (RR 0.22 95% CI 0.06-0.72 and RR 0.20 95% CI 0.05-0.72). Posaconazole was also found to be more effective than no prophylaxis/placebo in reducing all-cause mortality (RR 0.56, 95% CI 0.30-0.98). Posaconazole had the highest probability of being the most effective agent in reducing IFI risk and all-cause mortality.
  
  
  CONCLUSIONS
  IFI prophylaxis has a positive effect on IFI risk reduction. However, its effect on all-cause mortality is not as pronounced. The analysis has additionally pinpointed posaconazole as potentially the most effective IFI prophylaxis in neutropenic patients.
authors: Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors: Petros
authors: P
authors: Pechlivanoglou
authors: Hoa H
authors: HH
authors: Le
authors: Simon
authors: S
authors: Daenen
authors: John A
authors: JA
authors: Snowden
authors: Maarten J
authors: MJ
authors: Postma
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents
keywords: IFIs; antifungals; evidence synthesis