ESA Therapy for Kidney Patients: Is It Ever Safe?
ESA Therapy for Kidney Patients: Is It Ever Safe?
Hello. This is Jeffrey Berns from the University of Pennsylvania School of Medicine in Philadelphia. I am Editor-in-Chief of Medscape Nephrology.
It has been an interesting week for erythropoietin-stimulating agent (ESA) therapy in patients with chronic kidney disease (CKD) and dialysis. I hope everyone has seen the US Food and Drug Administration (FDA) alerts and changes in the package inserts for ESAs. The big changes are new black box warnings pointing out that hemoglobin levels above 11 g/dL in CKD and dialysis patients have been associated with death, cardiovascular risk, and stroke. No safe level of hemoglobin or safe dose of ESA has been established in these patients.
The new FDA recommendations in the package insert are to initiate ESA therapy in patients with CKD when the hemoglobin is below 10 g/dL and to stop or reduce ESA therapy dosing when the hemoglobin level is above 10 g/dL, now really targeting avoidance of transfusion and allosensitization for potential kidney transplant patients. In dialysis patients, a 10- to 11-g/dL hemoglobin range has been recommended, with initiation of therapy when the hemoglobin falls below 10 g/dL. The consideration of the rate of fall is largely again focused on the avoidance of transfusion in these patients.
It will be interesting to see what impact this has on the Centers for Medicare and Medicaid Service's recommendation to remove the quality improvement measure related to the percentage of patients in a dialysis facility with hemoglobins below 10 g/dL. It is certainly very likely that we are going to see a big increase in the number of these patients in the hemodialysis population and, I suspect, in the CKD population as well.
Most of this information is extrapolated from the TREAT [Trial to Reduce Cardiovascular Events With Aranesp Therapy] study, which most closely mirrors the hemoglobin levels that the FDA alert and the ESA manufacturers have agreed to in their package insert. I should point out that the package insert for epoetin still recommends 3-times-weekly dosing for patients with CKD who are not on dialysis. Obviously, this is not what is practiced.
We will have to see what impact this has on patients. I have expressed concern before about the application of the results primarily from a single clinical trial (although there are other supporting data) with a very specific defined patient population to the entire spectrum of patients with CKD and end-stage renal disease. Outside the confines of a trial, in clinical practice, we all know that things are not as closely monitored and regulated as they are within the confines of a clinical trial. So I have some concerns about what is going to be happening to our patients, particularly those who don't closely reflect the patient populations who participated in the most recent clinical trials. I have expressed concern before about the young patient and relatively healthy patient without extensive comorbidity.
We will have to keep an eye on what happens here. I am sure we will see lots of editorializing and publications over the upcoming months and years as to the impact of this labeling change and FDA-mandated black box warning. If you have comments, please submit them through the Medscape pages. I look forward to hearing from you. This is Jeffrey Berns from the University of Pennsylvania School of Medicine.
Hello. This is Jeffrey Berns from the University of Pennsylvania School of Medicine in Philadelphia. I am Editor-in-Chief of Medscape Nephrology.
It has been an interesting week for erythropoietin-stimulating agent (ESA) therapy in patients with chronic kidney disease (CKD) and dialysis. I hope everyone has seen the US Food and Drug Administration (FDA) alerts and changes in the package inserts for ESAs. The big changes are new black box warnings pointing out that hemoglobin levels above 11 g/dL in CKD and dialysis patients have been associated with death, cardiovascular risk, and stroke. No safe level of hemoglobin or safe dose of ESA has been established in these patients.
The new FDA recommendations in the package insert are to initiate ESA therapy in patients with CKD when the hemoglobin is below 10 g/dL and to stop or reduce ESA therapy dosing when the hemoglobin level is above 10 g/dL, now really targeting avoidance of transfusion and allosensitization for potential kidney transplant patients. In dialysis patients, a 10- to 11-g/dL hemoglobin range has been recommended, with initiation of therapy when the hemoglobin falls below 10 g/dL. The consideration of the rate of fall is largely again focused on the avoidance of transfusion in these patients.
It will be interesting to see what impact this has on the Centers for Medicare and Medicaid Service's recommendation to remove the quality improvement measure related to the percentage of patients in a dialysis facility with hemoglobins below 10 g/dL. It is certainly very likely that we are going to see a big increase in the number of these patients in the hemodialysis population and, I suspect, in the CKD population as well.
Most of this information is extrapolated from the TREAT [Trial to Reduce Cardiovascular Events With Aranesp Therapy] study, which most closely mirrors the hemoglobin levels that the FDA alert and the ESA manufacturers have agreed to in their package insert. I should point out that the package insert for epoetin still recommends 3-times-weekly dosing for patients with CKD who are not on dialysis. Obviously, this is not what is practiced.
We will have to see what impact this has on patients. I have expressed concern before about the application of the results primarily from a single clinical trial (although there are other supporting data) with a very specific defined patient population to the entire spectrum of patients with CKD and end-stage renal disease. Outside the confines of a trial, in clinical practice, we all know that things are not as closely monitored and regulated as they are within the confines of a clinical trial. So I have some concerns about what is going to be happening to our patients, particularly those who don't closely reflect the patient populations who participated in the most recent clinical trials. I have expressed concern before about the young patient and relatively healthy patient without extensive comorbidity.
We will have to keep an eye on what happens here. I am sure we will see lots of editorializing and publications over the upcoming months and years as to the impact of this labeling change and FDA-mandated black box warning. If you have comments, please submit them through the Medscape pages. I look forward to hearing from you. This is Jeffrey Berns from the University of Pennsylvania School of Medicine.
