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LETTER

Interferon-{alpha} Treatment and Formation of Factor VIII Antibodies

right arrow Mike Makris, MA, MD, and F. Eric Preston, MD

15 May 1997 | Volume 126 Issue 10 | Page 829


TO THE EDITOR:

In their small controlled study, Mauser-Bunschoten and colleagues [1] found the same incidence of antibodies to factor VIII (inhibitors) in hemophiliacs treated with interferon-{alpha} as in the untreated control group. The authors concluded that interferon-{alpha} does not increase the risk for development of factor VIII inhibitors. The incidence of new inhibitors in the control group, however, is 92 cases per 1000 patient-years; this rate is more than 20 times greater than that previously reported in the Netherlands (4.4 per 1000 patients-years) [2]. Furthermore, at approximately the same time during which their interferon-{alpha} trial was being conducted, an unexpected and sudden increase in inhibitors occurred in their center that was related to a new pasteurized factor VIII concentrate [2]. It is clearly important to know whether any of the patients in this study received the implicated factor VIII product.

Since 1987, we have treated 36 hemophiliacs with interferon and have seen only one case of a new factor VIII antibody. This patient is a 44-year-old man with severe hemophilia A. He is negative for human immunodeficiency virus but positive for antibody to hepatitis C virus. A liver biopsy specimen obtained in 1989 revealed chronic persistent hepatitis; as a result, the patient received interferon-{alpha} 2b for 6 months. He had a transient response and relapsed soon after interferon therapy was discontinued. In 1992, the patient was treated with a 1-year course of interferon-{alpha} 2a and once again had a transient response. Four months after discontinuation of interferon treatment, however, he developed factor VIII inhibitors with a human level of 30 Bethesda units and a porcine level of 4 Bethesda units (he has never been exposed to porcine factor VIII). During the last 3 years, the level of the human inhibitor has decreased to 2.7 Bethesda units; the porcine inhibitor is now undetectable.

The size of Mauser-Bunschoten and colleagues' study and the extremely high incidence of inhibitors in their control group make it highly unlikely that the authors would have detected a significant increase in inhibitor development after interferon-{alpha} treatment.


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Royal Hallamshire Hospital, Sheffield, S10 1SG, United Kingdom


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1. Mauser-Bunschoten EP, Damen M, Reesink HW, Roosendaal G, Chamuleau RA, van den Berg HM. Formation of antibodies to factor VIII in patients with hemophilia A who are treated with interferon for chronic hepatitis C. Ann Intern Med. 1996; 125:297-9.

2. Rosendaal FR, Nieuenhuis HK, van den Berg HM, Heijboer H, Mauser-Bunschoten EP, van der Meer J, et al. A sudden increase in factor VIII inhibitor development in multitransfused haemophilia A patients in The Netherlands. Blood. 1993; 81:2180-6.

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