Linked Life Data

15824129

Source:http://linkedlifedata.com/resource/pubmed/id/15824129

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-4-12
pubmed:abstractText
A substantial increase in the incidence of pure red cell aplasia (PRCA) associated with recombinant human erythropoietin (epoetin) treatment occurred in 1998. The upsurge of antibody-mediated PRCA was almost exclusively associated with chronic kidney disease patients who received subcutaneous epoetin therapy and the formulation of epoetin-alpha distributed outside the USA (EPREX/ERYPO). A systematic programme of technical, immunological and epidemiological investigations was initiated to identify the possible causes. The potential causes were evaluated on the basis of the following criteria: temporal correlation with the increase in incidence of PRCA, significant difference between EPREX/ERYPO and other epoetin products, sufficient concentration in the product to elicit a weak immune response, evidence of immunogenic activity in animals supportive, and consistent with available clinical data. Organic compounds that were leached from rubber stoppers through the action of polysorbate 80 were detected in pre-filled syringes with uncoated rubber stoppers containing polysorbate 80-formulated EPREX/ERYPO (introduced outside the USA in 1998). The leachates were not present when the stoppers were coated, in the product formulated with human serum albumin or in other epoetin products. The adjuvant activity of the leachates was demonstrated in mice. The incidence of PRCA was significantly higher in patients exposed to the polysorbate 80 formulation of epoetin-alpha delivered from pre-filled syringes with uncoated rubber stoppers, which were recalled in 2003, than in patients exposed to the same formulation from syringes with coated rubber stoppers. In conclusion, these data strongly suggest that leachates were the critical contributory factor in the increased incidence of antibody-mediated PRCA attributed to EPREX/ERYPO.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0931-0509
pubmed:author
pubmed:issnType
Print
pubmed:volume
20 Suppl 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
iii33-40
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Epoetin-associated pure red cell aplasia in patients with chronic kidney disease: solving the mystery.
pubmed:affiliation
Service d'Hématologie Biologique, Hôpital Hôtel-Dieu, 1 Place du Parvis Notre Dame, 75181 Paris Cedex 4, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't