Method: Medical databases were searched for randomized trials and observational studies reporting hematological AE associated with pegylated interferon plus ribavirin for CHC in patients with stage 3 or 4 fibrosis. Qualified studies were reviewed to extract patient’s baseline characteristics, information on disease and treatment, and clinical outcomes including hematologic AE, dose reduction and treatment discontinuation due to hematological AE, and sustained viral response (SVR). Single-arm meta-analysis was performed on patients treated by pegylated interferon plus ribavirin to estimate the risks of hematological AE and its related dose reduction and treatment discontinuation. Meta-regression analysis was conducted to explore predictors for dose reduction due to hematological AE and the association between hematological AE related dose reduction and SVR.
Result: Six randomized trials and 19 observational studies including 2,695 patients receiving pegylated interferon plus ribavirin for their advanced fibrosis and CHC (mean age: 51.0 years; male: 67.9%; mean body mass index (BMI): 26.9 kg/m2; cirrhosis: 84.7%; viral genotype 1/4/5/6: 66.6%; mean alanine transaminase: 112 U/l; and mean albumin: 38.6 g/l). The common hematological AE observed in the 25 studies included anemia (34.1%, 95% CI 26.1% to 43.2%), neutropenia (43.0%, 95% CI 33.9% to 52.6%), and thrombocytopenia (38.7%, 95% CI 31.2% to 46.8%). 25.4% (95% CI 23.0% to 27.9%) of patients had dose reduction and 6.1% (95% CI 4.8% to7.8%) had treatment discontinuation due to hematological AE. Meta regression suggested that BMI (coefficient 0.217, P<0.001); male (coefficient 4.801, P<0.001); baseline neutrophil counts (coefficient -4.434, P<0.001) and platelet counts (coefficient -2.493, P=0.001) were significantly associated with the risk of dose reduction caused by hematological AE. Dose reduction caused by hematological AE likely reduced SVR of pegylated interferon plus ribavirin by more than two times (coefficient -2.671, P<0.001).
Conclusion: More than one-third of patients with CHC and advanced fibrosis receiving pegylated interferon plus ribavirin experienced anemia, neutropenia, and thrombocytopenia that required dose reduction. High BMI, male gender, cirrhosis, low baseline neutrophil counts and platelet counts significantly increased the risk of dose reduction caused by hematological AE and substantially reduced the response to pegylated interferon plus ribavirin.
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