Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: Direct and indirect treatment comparison meta-analysis

Background: Valganciclovir (VGC) 900 mg is approved for CMV prophylaxis, but it has been associated with 10%-40% leucopenia rate. We hypothesize that VGC 450 mg daily may be as effective as and safer than 900 mg daily. Methods: Studies evaluating valganciclovir 900 mg and 450 mg daily against controls were evaluated. Direct comparisons were performed by random-effects models and indirect comparisons by the Bucher method. Results: Twelve trials with VGC 900 mg (1543 patients) and 8 trials with VGC 450 mg (1531 patients) were included. The risk of CMV disease with VGC 900 mg versus controls was 1.06 (95% confidence interval [CI],.64-1.76; P =.81; I2=29%) and with VGC 450 mg vs controls.77 (95%CI,.49-1.18; P =.23; I2=24%). The risk of leucopenia was 5.24 (2.09-13.15; P =.0004; I2=44%) for VGC 900 mg versus controls and 1.58 (.96-2.61; P =.07; I2=36%) for VGC 450 mg versus controls; the risk for acute allograft rejection was 1.71 (.45,-6.50; P =.43) for VGC 900 mg and.80 (.50-1.28; P =.34) for VGC 450 mg. Adjusted indirect comparison between VGC 900 mg and VGC 450mg: the risk for CMV disease was not significantly different: odds ratio (OR), 1.38 (.84-2.25); P =.19; the risk of leucopenia was significantly increased with VGC 900 mg: 3.32 (1.76-6.26); P =.0002; and the risk of rejection was significantly increased with VGC 900 mg: 2.56 (1.50-4.53); P =.0005. Results remained consistent after adjustments by allograft, CMV control strategy, and immunosuppression. Conclusions. Valganciclovir 900 mg showed no superiority efficacy compared to controls (ganciclovir or preemptive) and equivalent efficacy to VGC 450 mg (statistical power: 94% and 97%, respectively) for CMV universal prophylaxis.VGC 900 mg was significantly associated with 3 times increase in the risk of leucopenia and 2 times increase in the risk of rejection compared with VGC 450 mg.