Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: a systematic review with meta-analysis and trial sequential analysis

Abstract

Invasive fungal infections are a potentially life-threatening complication in immunocompromised patients. The aim of this study was to assess the efficacy and safety of posaconazole as compared with other antifungal agents for preventing invasive fungal infections in immunocompromised patients. Embase, CENTRAL, and MEDLINE were searched for randomized conweekmonthtrolled trials (RCTs) up to June 2020. A systematic review with meta-analysis of RCTs was performed using random-effects model. Trial sequential analysis (TSA) was conducted for the primary outcome to assess random errors. A total of five RCTs with 1,617 participants were included. Posaconazole prophylaxis was associated with a significantly lower risk of IFIs (RR, 0.43 [95% CI 0.28 to 0.66, p = 0.0001]) as compared to other antifungal agents. No heterogeneity was identified between studies (I 2 = 0%). No significant associations were observed for the secondary outcomes measured, including risk reduction of invasive aspergillosis and candidiasis, clinical failure, all-cause mortality, and treatment-related adverse events, except for infection-related mortality (RR, 0.31 [95% CI 0.15 to 0.64, p = 0.0001]). Subgroup analysis favoured posaconazole over fluconazole for the prevention of IFIs (RR, 0.44 [95% CI 0.28 to 0.70, p = 0.0004]). TSA confirmed the prophylactic benefit of posaconazole against IFIs. Posaconazole is effective in preventing IFIs among immunocompromised patients, particularly those with hematologic malignancies and recipients of allogenic hematopoietic stem cell transplantation.

Efficacy of Photobiomodulation in the Treatment of Cancer Chemotherapy-Induced Oral Mucositis: A Meta-Analysis with Trial Sequential Analysis

“…In pairwise meta-analysis, it is not possible to differentiate whether the meta-analysis is underpowered, and the results can be deemed conclusive [ 21 ]. Nevertheless, it is essential to address whether an intervention being investigated is truly effective or not so that it can help researchers as well as policy-makers to assess whether further trials would add informative value or not [ 30 ]. Trial sequential analysis can be useful to tackle this concern by differentiating whether the pairwise meta-analyses deliver sufficient evidence for the evaluation of the intervention [ 21 , 30 ].…”

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

“…It is labelled for prophylaxis of invasive yeast and mold infections in high-risk immunocompromised patients with leukaemia. 11 Dasatinib is metabolized in the liver by the CYP450 isoenzyme CYP3A4 and is subject to drug interactions with CYP3A4 inhibitors. 12,13 Ketoconazole, a classic CYP3A4 inhibitor, increases dasatinib exposure by nearly five-fold in patients, correlated with an increase in corrected QT values of approximately 6 msec.…”

“…It is labelled for prophylaxis of invasive yeast and mold infections in high-risk immunocompromised patients with leukaemia. 11 …”

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

“…VCZ has good bioavailability, but owing to a higher cost, scarcity of studies on CNS penetration, and altered pharmacokinetics in the context of inflammation, its use is limited [ 115 ]. Although other triazoles such as itraconazole, posaconazole, and prodrug isavuconazole [ 116 , 117 ] exhibit anticryptococcal activity, they are only used as a second-line agent or in combination with AmB due to drug–drug interactions and toxicity (reviewed in [ 118 ]).…”