Correspondence

A Peptide-Based Erythropoietin-Receptor Agonist for Pure Red-Cell Aplasia

N Engl J Med 2010; 362:656-657February 18, 2010

Article

To the Editor:

In their study of a peptide-based erythropoietin-receptor agonist (Hematide, Affymax) for pure red-cell aplasia, Macdougall et al. (Nov. 5 issue)1 suggest that discontinuation of epoetin therapy and initiation of treatment with the peptide-based erythropoietin-receptor agonist can increase hemoglobin levels to target values; clearance of antierythropoietin autoantibodies occurred in at least 6 of 14 patients. Whether continued administration of the peptide-based erythropoietin-receptor agonist is required to maintain the hemoglobin value once target values have been reached remains unknown: the disappearance of antierythropoietin antibodies could eventually result in a sufficient level of endogenous erythropoietin to maintain target hemoglobin levels in some patients. Since the trial did not assess serum erythropoietin levels, I suggest that a retrospective evaluation of serum samples should be performed to determine erythropoietin levels before discontinuation of the drug is considered in patients with undetectable autoantibodies. This point is crucial given both the high cost of long-term treatment with novel erythropoiesis-stimulating agents and the potential loss of response owing to the synthesis of neutralizing antibodies (as occurred in Patient 10 in the article by Macdougall et al.).

Since a limited course of corticosteroids plus low-dose cyclophosphamide can effectively treat erythropoietin-induced pure red-cell aplasia in up to 87% of patients,2 I think that treatment with the peptide-based erythropoietin-receptor agonist should be reserved for patients who have not had a response to treatment for pure red-cell aplasia and for patients who continue to require erythropoiesis-stimulating agents after resolution of pure red-cell aplasia.

Daniele Focosi, M.D.
University of Pisa, Pisa, Italy
dfocosi@tin.it

No potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   Macdougall IC, Rossert J, Casadevall N, et al. A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. N Engl J Med 2009;361:1848-1855
   Full Text | Web of Science | Medline

2. 2

   Verhelst D, Rossert J, Casadevall N, Kruger A, Eckardt KU, Macdougall IC. Treatment of erythropoietin-induced pure red cell aplasia: a retrospective study. Lancet 2004;363:1768-1771
   CrossRef | Web of Science | Medline

Author/Editor Response

In response to Focosi, we do not believe that the hemoglobin levels would be maintained after discontinuation of treatment with the peptide-based erythropoietin-receptor agonist (Hematide). It is unlikely that endogenous erythropoietin production would be sufficient in these patients, since they were originally started on erythropoietic agents because of renal-related anemia caused largely by erythropoietin deficiency. In addition, if the patients had become less dependent on the peptide-based erythropoietin-receptor agonist, we should have seen a reduction in the required median dose of the drug. We did not observe this. Because of a large interindividual variability in serum erythropoietin levels, these levels are not considered to be useful in either diagnosing this type of anemia or in predicting the response to therapy with erythropoiesis-stimulating agents.1

Since this drug is not yet commercially available, the price has not been set, but we have no reason to believe that the costs of treatment will exceed those of existing erythropoietic agents. Although Focosi is correct that we previously reported that some patients with antibody-mediated pure red-cell aplasia have a response to immunosuppressive medication,2 on the basis of our experience with both therapies and the available data, we believe that the peptide-based erythropoietin-receptor agonist has a much more favorable ratio of benefit to risk than immunosuppressive therapy.

Iain C. Macdougall, M.D.
King's College Hospital, London, United Kingdom
iain.macdougall@kch.nhs.uk

Nicole Casadevall, M.D.
Hôpital Saint Antoine, Paris, France

Kai-Uwe Eckardt, M.D.
University of Erlangen-Nuremberg, Erlangen, Germany

Since publication of their article, the authors report no further potential conflict of interest.

2 References

1. 1

   Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19:Suppl 2:ii1-ii47
   CrossRef | Medline

2. 2

   Verhelst D, Rossert J, Casadevall N, Kruger A, Eckardt KU, Macdougall IC. Treatment of erythropoietin-induced pure red cell aplasia: a retrospective study. Lancet 2004;363:1768-1771
   CrossRef | Web of Science | Medline