11Update on erythropoiesis-stimulating agents
Section snippets
Post-approval clinical trials
Subsequent to Food and Drug Administration (FDA) approval for use of ESA to reduce allogeneic blood transfusions, a number of clinical trials were undertaken in an attempt to demonstrate long-term improved patient outcomes with ESA therapy. These trials are summarised in Table 2.12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 In elective spine surgery, blood transfusion and patient outcomes were compared for ESA and placebo-treated cohorts. These patients did not receive
Reimbursement and regulatory considerations
In July 2007, Centers for Medicare and Medicaid Services (CMS) issued a national coverage decision (NCD), restricting reimbursement for ESAs to treat chemotherapy-induced anaemia in cancer patients, only to cases in which Hgb levels prior to initiation of ESA are <10 g dl−1.46 The CMS decision was in the context of a series of revisions by the FDA on the label for ESAs,47, 48 following the clinical trials presented above, which showed increased adverse events and higher mortality in cancer
Risk management
The FDA has required that ESAs must be prescribed under a risk management programme, known as a Risk Evaluation and Mitigation Strategy (REMS), to ensure the safe use of these drugs.75 REMS programmes are in place for over 95 other pharmaceuticals, including therapies used in patients with malignancies. These programmes underscore the reality that the practice of medicine includes the use of FDA-approved medications beyond narrow specifications in the label. For ESAs, targeting and maintaining
Role of ESA therapy in cardiac surgery
An unresolved question is the safety of ESA therapy in cardiac surgery patients and its role in this setting. In a European trial,79 the authors found no differences in mortality, thrombotic events or serious adverse events among their 76 patients, whether treated with ESA or placebo, nor any differences in haemostatic parameters during the 14-day preoperative interval during which increased levels of haematocrit (from 42 ± 3% to 48 ± 3%) were demonstrated.80 In fact, the investigators were
Conclusion
Since its approval more than two decades ago, ESA therapy has expanded both on-label and off-label beyond renal failure into a variety of clinical scenarios. Although allogeneic transfusions have been reduced as a result of ESA use, debated data suggest that this therapy can result in negative outcomes for specified patient populations. As with transfusion therapy, selection of both targeted population and suitable dosing will result in appropriate use of these agents. The cost and outcome
Acknowledgement
Conflict of interest
LTG is a consultant for Amgen.
AS is a consultant for: CSL Behring King of Prussia, PA; HemoCue Madison, NJ; Masimo Corporation Irvine, CA; Vifor Pharma Ltd. Glattbrugg, Switzerland.
AS grant/research: CSL Behring King of Prussia, PA.
AS speaker with honorarium: CSL Behring King of Prussia, PA;
Masimo Corporation Irvine, CA.
Funding source
None.
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2015, Clinics in Laboratory MedicineCitation Excerpt :The clinical utility of reticulocyte Hb content has been well established as a reliable marker of FID in hemodialysis patients, exhibiting high specificity and sensitivity in the management of intravenous iron therapy. Although ESA treatment has been approved for anemia in several settings outside CKD, appropriate studies still need to be performed to assess the suitability of CHr and/or percentage of Hypo-He concerning the detection of FID in other disease-related anemias, and in the reduction of ESA doses and duration of treatment.170–174 Reticulocyte Hb improves the monitoring of erythropoietic response to intravenous iron administration in ID anemia.
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