title: A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia.
abstract: BACKGROUND
  We investigated whether a novel, synthetic, peptide-based erythropoietin-receptor agonist (Hematide, Affymax) can stimulate erythropoiesis in patients with anemia that is caused by antierythropoietin antibodies.
  
  
  METHODS
  In this open-label, single-group trial, we enrolled patients with chronic kidney disease who had pure red-cell aplasia or hypoplasia due to antierythropoietin antibodies and treated them with a synthetic peptide-based erythropoietin-receptor agonist. The agonist was administered by subcutaneous injection at an initial dose of 0.05 mg per kilogram of body weight every 4 weeks. The primary end point was a hemoglobin concentration above 11 g per deciliter without the need for transfusions.
  
  
  RESULTS
  We treated 14 patients with the peptide agonist for a median of 28 months. The median hemoglobin concentration increased from 9.0 g per deciliter (with transfusion support in the case of 12 patients) before treatment to 11.4 g per deciliter at the time of the last administration of the agonist; transfusion requirements diminished within 12 weeks after the first dose, after which 13 of the 14 patients no longer required regular transfusions. Peak reticulocyte counts increased from a median of 10x10(9) per liter before treatment to peak counts of greater than 100x10(9) per liter. The level of antierythropoietin antibodies declined over the course of the study and became undetectable in six patients. One patient who initially responded to treatment had a diminished hematologic response a few months later despite increased doses of the agonist and required transfusions again; this patient was found to have antibodies against the agonist. One patient died 4 months after the last dose of the agonist, and a grade 3 or 4 adverse event occurred in seven other patients during the study period.
  
  
  CONCLUSIONS
  This novel agonist of the erythropoietin receptor can correct anemia in patients with pure red-cell aplasia caused by antierythropoietin antibodies. (ClinicalTrials.gov number, NCT00314795.).
authors.affiliation: Department of Renal Medicine, King's College Hospital, London. ain.macdougall@kch.nhs.uk
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.forename: Jerome
authors.initials: J
authors.lastname: Rossert
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.forename: Richard B
authors.initials: RB
authors.lastname: Stead
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Duliege
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D004921:Erythropoietin / Q000009:adverse effects / Q000276:immunology; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017467:Receptors, Erythropoietin / Q000819:agonists*; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006454:Hemoglobins; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin