Editor -A senior nephrologist visited us in Boston about 2 weeks back and I took him out to lunch at the Elephant Walk, a nice Cambodian-French restaurant in Brookline. We caught up on what we'd been doing over the past 6 months or so. He mentioned to me that my name had come up in conversations with some senior executives in the anemia business, you know the type I mean. They told him that my views on anemia are “rabid”. So, naturally, I looked up "rabid" in the online Merriam-Webster dictionary. Rabid means “going to extreme lengths in expressing or pursuing a feeling, interest, or opinion”. Interestingly, my so-called “rabid” views are part of the FDA label for ESAs, and may be part of new anemia guidelines. So what are these “rabid” recommendations on anemia that seem to be bothering some industry executives? (Incidentally, because we are nearing Halloween, I submit to you a particularly ghoulish picture of a rabid dog, apologies in advance).
Commentary - Dr. Ajay K. Singh
1. Individualize Anemia Management
For every patient we should identify the hemoglobin (Hb) concentration at which an intervention is needed because of either symptoms or another medical indication (for example, angina, worsening heart failure). The intervention could be iron or ESA or a blood transfusion. Using one or more maneuvers to keep the patient above their Hb trigger should be a key goal of anemia treatment. Every patient will have their own precise Hb trigger -- it will probably be somewhere between 9 and 10 g/dL for most, but it might be a bit higher for some patients.
For every patient we should identify the hemoglobin (Hb) concentration at which an intervention is needed because of either symptoms or another medical indication (for example, angina, worsening heart failure). The intervention could be iron or ESA or a blood transfusion. Using one or more maneuvers to keep the patient above their Hb trigger should be a key goal of anemia treatment. Every patient will have their own precise Hb trigger -- it will probably be somewhere between 9 and 10 g/dL for most, but it might be a bit higher for some patients.
On June 24, 2011, the US Food and Drug Administration (FDA) made a major modification to the ESA label (1). The FDA emphasized that treatment of chronic kidney disease (CKD) anemia with ESA therapy should be individualized; and, the FDA pointed out, no hemoglobin target level or ESA dosing strategy should be considered without adverse risk. In an article in Dialysis and Transplantation I discuss clinical scenarios as examples of individualization.
By individualizing ESA dosing we are very likely to reduce dosages markedly for some and perhaps increase ESA dosages for others. Besides, this is a safer strategy. Of course this means we will need to get rid of anemia protocols, neural networks for ESA dosing, and automated computerized algorithms.
2. Use the lowest possible dose of ESA
Several observational studies provide evidence that strongly suggests that high ESA doses are associated with worse outcome. This is true for both dialysis and non-dialysis patients.
If one sets aside the profit motive, there should be no reason to use higher doses of ESAs just for the sake of using ESA. The FDA emphasized that there should be a shift away from aiming for a hemoglobin (Hb) target range of 10 to 12 g/dL of Hb to one of using the lowest possible dose of ESA to prevent a blood transfusion.
Since subcutaneous administration of ESA results, on average, in about 1/3rd lower dose of ESA to attain any particular Hb concentration compared to intravenous administration, shifting to ESA administered via the subcutaneous route makes a lot of sense.
3. Minimize blood transfusions in transplant eligible patients
Exposure to a blood transfusion results in allosensitization. In turn, allo-sensitization results in an increase in panel reactivity. Avoiding blood transfusion in transplant eligible patients should be a key goal for managing anemia in CKD patients, especially those patient's on dialysis. Using ESA and iron to manage these patients makes sense, but use the lowest possible dose.
Bottom line: Industry executives need to look inwards about what motivates their views. It's not all about shareholder value, margins, market share and the like. Amid all of this we have patient's. These industry "oligarchs” (borrowing a phrase from my favorite commentator Paul Krugman) need to be reminded of the Mark Twain quote "To a man with a hammer, everything looks like a nail."
