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        Etanercept May Have Caused Aplastic Aanemia in a Patient Treated for Arthritis

        A DGReview of :"Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor"
        European Journal of Haematology

        12/31/2003
        By Emma Hitt, PhD


        A case report of a patient describes the development of aplastic anaemia complicated by sepsis after the patient received etanercept, and this may be the first report of aplastic anaemia associated with tumour necrosis factor-alpha (TNF-alpha) blockade.

        Upregulation of TNF-alpha has been implicated in the pathogenesis of several inflammatory conditions, including rheumatoid arthritis. Therapeutic agents that block TNF-alpha activity have shown to be effective for the treatment of these conditions.

        In their report, John Kuruvilla, MD, with the University of British Columbia, Vancouver, Canada, and colleagues describe the case of a 78-year-old man diagnosed with rheumatoid arthritis and treated with etanercept.

        The patient was first treated with oral methotrexate. He had also been treated for hypertension and type 2 diabetes mellitus for approximately 15 years with no recent changes in doses or medications.

        The patient was started on etanercept at a dose of 25 mg subcutaneously twice a week in May 2002 for symptoms of rheumatoid arthritis in the hands. In July 2002, after 16 weeks of therapy with etanercept, the patient developed malaise associated with anorexia and weakness, and was determined to be pancytopaenic.

        On arrival, the patient was delirious and in atrial fibrillation with a rapid ventricular response, requiring admission to the coronary care unit for rate control. At last follow up on October 22,2002, 12 weeks after presentation, the patient remained clinically well with normal blood counts.

        "This patient had stable blood counts prior to the institution of therapy with etanercept. The patient had been maintained on a stable dose of methotrexate for over 3 years with no significant effects on blood counts, and other medications were unchanged," the authors point out. "Methotrexate or other medications were thus unlikely to be the causative agent in precipitating aplasia, although a synergistic effect cannot be ruled out," they add.

        "To our knowledge, this is the first report of aplastic anemia related to TNF-alpha inhibition. With the increasing use of anti-TNF agents for a variety of indications, the potential for hematologic toxicity should be noted and closely monitored," Dr. Kuruvilla and colleagues conclude.

        According to the researchers, the exact mechanism is unclear, but TNF-alpha is known to affect the growth of haematopoietic stem cells, which may result in peripheral cytopaenias.
        Eur J Haematol. 2003;71:396-398. "Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor"

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