Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project

Bennett, Charles L.; Cournoyer, Denis; Carson, Kenneth R.; Rossert, Jérôme; Luminari, Stefano; Evens, Andrew M.; Locatelli, Francesco; Belknap, Steven M.; McKoy, June M.; Lyons, Erica; Kim, Benjamin; Sharma, Raj; Costello, S.; Toffelmire, Edwin B.; Wells, George A.; Messner, Hans A.; Yarnold, Paul R.; Trifilio, Steven; Raisch, Dennis W.; Kuzel, Timothy M.; Nissenson, Allen R.; Lim, Lay Cheng; Tallman, Martin S.; Casadevall, Nicole

doi:10.1182/blood-2005-02-0508

Cited by 91 publications

(66 citation statements)

References 30 publications

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“…Therefore, in our case, the induction of autoimmunity to the pegylated glycoprotein is the most probable pathogenesis of PRCA development including the inhibition of erythropoiesis, although we cannot exclude other possibilities because PRCA itself is an incidental complication in HD patients [11]. Regarding the treatment of PRCA associated with ESA therapy, it has previously been reported that PRCA did not improve without immunosuppressive treatment [21]. The largest retrospective study, including 47 patients with PRCA, reported that renal transplantation, corticosteroids, cyclosporine, and corticosteroids in combination with cyclophosphamide were considered effective therapies [22].…”

Section: Discussionmentioning

confidence: 75%

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

et al. 2015

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A 42-year-old man with end-stage renal failure had been receiving hemodialysis therapy since April 2009. Initially, darbepoetin alfa was administered to treat his renal anemia. After treatment was switched to epoetin beta pegol, the patient's hemoglobin levels rapidly decreased. He was diagnosed with pure red cell aplasia (PRCA) based on the results of a bone marrow examination. Epoetin beta pegol was strongly suspected to be the cause of the PRCA, and although he tested negative for anti-epoetin beta pegol antibodies, epoetin beta pegol was discontinued and cyclosporine therapy was initiated. Thereafter, his hemoglobin levels increased, and his anemia dramatically improved after 3 months.

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Section: Discussionmentioning

confidence: 75%

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

et al. 2015

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“…For NSF, reports of a gadodiamide-NSF relationship from Austria and Denmark were published three months apart and for PRCA, reports from the United States/Europe and Canada were published on the same day. 5,43,50,51 For RS, a preliminary report of the Arizona case-control study in the Morbidity and Mortality Weekly Report in July 1980 was followed by preliminary and final reports of Michigan and Ohio studies with similar findings six and 18 months later, respectively. 22-25 Regulatory responses were delayed and uncoordinated.…”

Section: Discussionmentioning

confidence: 99%

“…50 In 2005, the groups collaboratively reported that epoetinassociated PRCA disappeared following renal transplantation. 51 In 2009, epoetin-associated PRCA resolved in 13 of 14 patients who received a novel peptide-based erythropoietin-receptor agonist. 52 PRCA from increased use of subcutaneous epoetin was facilitated by several factors (Table 1).…”

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

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Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye’s syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States’ NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common

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“…Bennett et al (27) reported recovery rates from PRCA of 2% without immunosuppressive therapy, 52% after immunosuppressive treatment(s) outside the renal transplantation setting, and 95% after kidney transplantation. The relative importance of immunosuppression and normalization of kidney function after kidney transplantation in resolving ESA-induced PRCA has not been established.…”

Section: Treatment Of Esa-induced Prcamentioning

confidence: 99%

Pure Red Cell Aplasia Induced by Erythropoiesis-Stimulating Agents

Pollock¹,

Johnson²,

Hörl³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Pure red cell aplasia in patients who are treated for anemia of chronic kidney disease with erythropoiesis-stimulating agents such as epoetin was first reported in 1998. Although the incidence of pure red cell aplasia peaked in 2002, it remains important for nephrologists to know how to investigate a suspected case of pure red cell aplasia and how to identify other causes of hyporesponsiveness to erythropoiesis-stimulating agents, which account for the vast majority of such cases. The authors reviewed the current status of information in the literature and drew on their personal experiences with patients regarding the diagnosis and management of epoetin-induced pure red cell aplasia. The mechanism for development of epoetin-induced pure red cell aplasia remains unconfirmed. It generally occurs after the production of neutralizing anti-erythropoietin antibodies. Elucidation of a suspected pure red cell aplasia case requires a systematic approach, beginning with simple measurements such as blood cell counts, because most cases of erythropoiesis-stimulating agent hyporesponsiveness are attributable to other causes. If these criteria indicate that the patient's response to erythropoiesis-stimulating agent therapy is very poor, then bone marrow examination and measurement of anti-erythropoietin antibodies is justified. If pure red cell aplasia is confirmed, then cessation of erythropoiesis-stimulating agent therapy and initiation of immunosuppressive therapy are recommended. Continued study of epoetin-induced pure red cell aplasia is needed to help nephrologists prevent or manage future cases and will have implications for the use of other protein-based therapeutic agents.

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Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project

Abstract: Since its introduction in

Cited by 91 publications

References 30 publications

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Pure Red Cell Aplasia Induced by Erythropoiesis-Stimulating Agents

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