Comparable results have been reported by the Cochrane Group from an aggregated study data-based meta-analysis of ESA studies (Bohlius et al, 2006), where no significantly increased risk of mortality was seen between the ESA and control groups in those studies, which enrolled patients with baseline Hb levels <10 g dl−1 or in studies enrolling patients with baseline Hb levels 10 12 g dl−1.
A recent meta-analysis of ESAs has suggested that the increase in mortality in ESA-treated cancer patients undergoing chemotherapy is less pronounced than in those patients undergoing other anticancer treatments such as radiotherapy or no anticancer treatment (Bohlius et al, 2009a, 2009b).
To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events.
However, an analysis of 28 controlled ESA trials (6525 patients) in all oncology settings indicated that ESA use was associated with a higher relative risk for mortality (relative risk=1.15; 95% CI: 1.03 1.29) (Tonelli et al, 2009).
This risk is described in the ESA-product labelling (Amgen, 2011; Centocor Ortho Biotech Products, 2011) and can be managed clinically (of note, a recent exploratory analysis of a controlled-ESA trial suggested that administering anti-thrombotic therapy with ESAs may lower VTE rates) (Aapro et al, 2009a).
Others have chosen to consider both patient ESA dose and hemoglobin level expressed as erythropoietin resistance index ([ERI] IU/kg/week divided by hemoglobin in g/dL) with varying ERI thresholds for analysis: Lopez-Gomez et al. prospectively stratified their analysis of factors that condition ESA response by creating ERI groups of < 5, 5 15, and > 15 [ 26].
To explore ESA dose dependency, analysis was performed by creating 8 categories of ESA and Hb in HD patients.
The letter describes the official analysis of the impact of the ESA changes as "very limited" with no attempt to break down the limited data available to show how the cut will affect people with different forms of disability.
To explore dose dependent effects of ESA and Hb on mortality, analysis with more categories of ESA and Hb were conducted.
This confounds the analysis of clinical trials in which higher doses of ESA and higher Hb occur in those randomized to higher Hb targets.
