Correspondence

Recombinant Erythropoietin for Anemia in Inflammatory Bowel Disease

N Engl J Med 1996; 335:751-752September 5, 1996

Article

To the Editor:

In their study of recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease (March 7 issue),1 Schreiber et al. found that treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels. Usually, chronic anemia with hemoglobin levels between 7 and 8 g per deciliter is well tolerated by younger patients, because of a variety of compensatory mechanisms. In view of the only moderately decreased hemoglobin levels at the beginning of the trial (mean hemoglobin level in the placebo group, 8.69 g per deciliter; in the treatment group, 8.81 g per deciliter) and the young age of the study patients (median, 31 and 26 years, respectively), I doubt that treatment with erythropoietin had any clinical benefit. Were the patients studied symptomatic from anemia? Were efforts made to assess any potential improvement in clinical symptoms or quality of life?

Responsible use of medical resources is an important matter in determining new indications for the use of hematopoietic growth factors. Many interventional trials with granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor could not demonstrate a significant clinical benefit even though they effected obvious changes in the leukocyte count. Therefore, it seems inappropriate that the primary end point of this study should be a mere increase in a laboratory value, the hemoglobin level, rather than a measurable clinical response. The case for using erythropoietin to treat asymptomatic anemia in young patients with inflammatory bowel disease has not been made.

Thomas Fischer, M.D.
Johannes Gutenberg University, D-55101 Mainz, Germany

1 References

1. 1

   Schreiber S, Howaldt S, Schnoor M, et al. Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease. N Engl J Med 1996;334:619-623
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Fischer questions whether a reduction in hemoglobin values in patients with inflammatory bowel disease leads to a decrease in the quality of life. Anemia in chronic diseases is associated with reduced quality of life.1 In inflammatory bowel disease, the severity of anemia is an important part of the complex of symptoms represented in clinical indexes of disease activity.2 Patients with inflammatory bowel disease often report fatigue, weakness, loss of strength, and a reduced sense of general well-being — all symptoms also associated with chronic anemia.2

Our study was not designed to investigate quality of life as a primary measure in an improving condition, such as active inflammatory bowel disease that is being treated with antiinflammatory medications. Gasché et al. have studied the quality of life and the treatment of anemia in patients with chronic stable inflammatory bowel disease.3 Thirty-one patients with chronically active Crohn's disease and anemia (hemoglobin, <10.5 g per deciliter) were randomly assigned to receive either erythropoietin (150 U per kilogram of body weight three times weekly) or placebo in addition to intravenous iron saccharate. Hemoglobin values increased by more than 2.0 g per deciliter in 94 percent of the patients treated with erythropoietin and iron and 66 percent of the patients who received only intravenous iron saccharate (P<0.05). The response to iron alone was markedly slower than the response to erythropoietin plus iron. The increase in hemoglobin levels was smaller in the patients who received iron alone. In both groups, increased hemoglobin levels were associated with an improved quality of life.3 Increasing hemoglobin levels in patients with anemia associated with chronic disease also improves the quality of life markedly.1 Some suggest raising hemoglobin values to 14 g per deciliter.4 In young patients, therefore, adaptation to low hemoglobin levels could partly represent an adaptation to a lower quality of life.

We share Fischer's concern about the responsible use of health care resources. Anemia in inflammatory bowel disease is often a serious therapeutic challenge. To define a group of patients dependent on treatment with erythropoietin, we used a run-in phase in which we showed that 63 percent of patients had increased hemoglobin values after six weeks of treatment with oral iron. Thirty-five percent of patients did not improve with the administration of iron (that is, because of inadequately low levels of endogenous erythropoietin), but many responded to combination treatment with iron and erythropoietin.

Patients with inflammatory bowel disease and symptoms possibly associated with anemia, in whom other therapeutic options have been exhausted, benefit from erythropoietin therapy. In the case of such patients, we believe that general considerations about the availability of health care resources should not influence the individual physician's decision to administer a treatment when it is indicated.

Stefan Schreiber, M.D.
Herbert Lochs, M.D.
Charité University Hospital, 10117 Berlin, Germany

Andreas Raedler, M.D.
Tabea Center for Inflammatory Bowel Diseases, 22587 Hamburg, Germany

4 References

1. 1

   Krantz SB. Erythropoietin and the anaemia of chronic disease. Nephrol Dial Transplant 1995;10:Suppl 2:10-17
   Web of Science | Medline

2. 2

   Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI). Gastroenterology 1979;77:843-846
   Web of Science | Medline

3. 3

   Gasche C, Dejaco C, Waldhor T, et al. Double-blind, placebo controlled trial of erythropoietin and iron saccharate for anemia in Crohn's disease. Gastroenterology 1995;108:A821-A821 abstract.
   Web of Science

4. 4

   Paganini EP. In search of an optimal hematocrit level in dialysis patients: rehabilitation and quality-of-life implications. Am J Kidney Dis 1994;24:Suppl:S10-S16
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Konstantinos H. Katsanos, Athina Tatsioni, Dimitra Natsi, Dimitrios Sigounas, Dimitrios K. Christodoulou, Epameinondas V. Tsianos. (2011) Recombinant human erythropoietin in patients with inflammatory bowel disease and refractory anemia: A 15-year single center experience. Journal of Crohn's and Colitis
   CrossRef