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.
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.
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