2009: a requiem for rHuEPOs--but should we nail down the coffin in 2010?
The recombinant human erythropoietins and allied proteins (epoetin alfa, attempted copies and biosimilar variants of epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoetin theta, epoetin omega, darbepoetin alfa, and methoxy-polyethylene glycol-epoetin beta) are among the most successful and earliest examples of biotechnologically manufactured products to be used in clinical medicine. This article charts a brief history of their use in clinical medicine, mainly dealing with chronic kidney disease, paying special attention to how these agents were introduced into clinical medicine and what has happened subsequently; in 2009, there were several developments that could be regarded as a "perfect storm" in terms of the long-term use of these compounds in chronic kidney disease and oncology and, likely, elsewhere. We are now very much at a "crossroads," where mature reflection is required, because with the latest trials and meta-analyses, these therapies seem not only expensive but also very much a clinical tradeoff (increased risk of adverse effects versus a small gain in fatigue scores). How we arrived at this crossroads is a useful illustration of how easy it is, without properly designed randomized, controlled trials, to assume that clinical benefit must follow therapeutic interventions.
Goldsmith
David
D
Renal Department, Guy's Hospital, King's Health Partners, London, United Kingdom. david.goldsmith@gstt.nhs.uk
D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000266:history; D015415:Biomarkers / Q000097:blood; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006397:Hematinics / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000266:history; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D018570:Risk Assessment; D016896:Treatment Outcome
D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin