Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease

Authors: Schreiber S, Howaldt S, Schnoor M, Nikolaus S, Bauditz J, et al.
Source: New England Journal of Medicine. 334:619-23. March 7, 1996.
Institutions: Departments of Medicine. Hamburg and Berlin, Germany and Vienna, Austria.
Financial support: Deutsche Forschungsgemeinschaft.



Some patients with inflammatory bowel disease have anemia that is not responsive to iron administration and not due to folate or B12 deficiency. One hypothesis is that inflammatory cytokines decrease erythropoietin production and create resistance to the effect of erythropoietin, leading to a relative deficiency of this hormone. This study was a randomized, double-blind trial of recombinant erythropoietin (epoietin) in treating patients with inflammatory bowel disease and anemia refractory to iron therapy.


Results Authors' Discussion

These results support the hypothesis that the anemia of IBD is related to a relative deficiency in erythropoietin, mediated by inflammatory cytokines (such as interleukin 1-ß). This relative deficiency can be mitigated by therapeutic administration of erythropoietin, with subsequent improvement in the anemia. Further studies will be needed to determine the appropriate erythropoietin and iron doses to be used.


In an accompanying editorial, Dr. Catherine Lacombe from Paris, France notes that the indications for erythropoietin treatment are being extended to diseases other than chronic renal failure, such as the anemias accompanying cancer and the anemia of chronic disease. Because of the expense of erythropoietin therapy, and because not all patients respond to this treatment, markers of response are being sought, including baseline erythropoietin levels, response to initial treatment and indices of inflammation, such as the interleukin 1-ß activity.


This study demonstrates an impressive effect of erythropoietin on iron-resistant anemia in inflammatory bowel disease. As is so often the case with new techniques in medicine, the original indications will be steadily enlarged to encompass larger and larger groups of patients. From the anemia of renal disease, indications will extend to the various anemias of chronic disease and cancer, at great cost (and great profit for the manufacturer). Because of the cost of erythropoietin therapy, it will be necessary to determine which patients are most likely to benefit from it, to ensure that other causes of anemia are not ignored, and to determine at what levels of hemoglobin treatment is to be started and stopped.

As for the insights into the pathogenesis of the anemia of IBD, although it seems likely that inflammatory cytokines such as interleukin 1-ß are responsible for the anemia, the specific role of interleukin 1-ß vs. other cytokines (such as TNF-alpha) remains to be clarified. The presence of these cytokines is clearly a marker for disease severity.


Reader comments

Date: Sat, 16 Mar 1996
From: fyacoub <>

This article is very interesting, it pretty much proved what we knew all along, that inflammatory mediators play a crucial part in the pathogenesis of the anemia of chronic disease; however, before we rush to conclusions and start using Epogen in inflamatory diseases, I think we have to answer crucial questions:

1- we need a bigger trial (much bigger!) to be convinced that the results are valid.
2- can we apply the same results to different inflammatory processes, e.g. rheumatoid arthritis?
3- about 20-25% of CRF patients on Epogen will have a significant elevation of their blood pressure, a major cardiovascular risk factor.

In summary, I think we need further study before starting treating our patients with this expensive treatment.

Fadi Yacoub. 

September 5, 1996

Letters to the Editor about this article from the NEJM site. 

June 24, 1997

In an article from the May 15, 1997 Annals of Internal Medicine (from one of the groups that authored this study), the use of intravenous iron with and without erythropoietin was examined in Crohn's Disease. Intravenous iron achieved a response in 15 out of 20 patients; iron plus erythropoietin in 18 out of 19. This study is not directly comparable to the one summarized here, since in the newer study over half of the patients were unable to tolerate oral iron supplements. Nevertheless, given the substantial difference in price between iron and erythropoietin, this is an important finding.


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