Haematological Effects of Interferon-beta-1a (Rebif) Therapy in Multiple Sclerosis

Overview

Journal Drug Saf

Specialties Pharmacology
Toxicology

Date 2004 Sep 8

PMID 15350158

Citations 29

Authors

Peter Rieckmann

Paul OConnor

Gordon S Francis

Graham Wetherill

Enrica Alteri

Affiliations

Soon will be listed here.

Abstract

Introduction: Interferon-beta-1a (Rebif) is an established treatment for relapsing-remitting multiple sclerosis (MS) and haematological changes are commonly reported in clinical trials of this agent. The combined clinical trial and postmarketing safety database for subcutaneous interferon-beta-1a (Rebif) allows a comprehensive, retrospective assessment of both common and infrequent haematological effects associated with interferon-beta therapy.

Methods: Haematological laboratory abnormalities were analysed from six randomised, controlled clinical trials of subcutaneous interferon-beta-1a in MS, five of which were placebo-controlled. Treatment data were collected from 2482 patients for up to 6 months, 1178 patients for up to 2 years and 786 patients for up to 6 years. Total interferon-beta-1a doses ranged from 22 microg once weekly to 44 microg three times weekly. Postmarketing surveillance data were also analysed.

Results: Treatment with interferon-beta-1a led to asymptomatic dose-related reductions in all cell lineages under investigation, predominantly white blood cells. The greatest differences between interferon-beta-1a therapy and placebo were seen for total leucocyte and neutrophil counts. At least two-thirds of patients affected by cytopenia experienced the onset of cytopenia within the first 6 months of therapy. The majority of events were mild and generally resolved within 3--4 months, while continuing therapy. Dose reductions were uncommon and only a small proportion (6 of 727; 0.8%) of patients stopped treatment over 2 years because of haematological abnormalities when receiving the highest dose of interferon-beta-1a, 44 microg three times weekly. Postmarketing safety reports were similarly related to asymptomatic cytopenias, although one case of potentially related autoimmune haemolytic anaemia was reported.

Conclusion: Although haematological abnormalities are common and dose-related in patients with MS receiving interferon-beta-1a, the events are mainly mild and transient, with little impact on adherence to therapy. Haematological events are rarely of clinical significance and do not adversely affect the benefit-to-risk ratio that favours high-dose interferon-beta-1a therapy.

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References

Durelli L, Ferrero B, Oggero A, Verdun E, Bongioanni M, Gentile E . Autoimmune events during interferon beta-1b treatment for multiple sclerosis. J Neurol Sci. 1999; 162(1):74-83. DOI: 10.1016/s0022-510x(98)00299-8. View

Landau A, Castera L, Buffet C, Tertian G, Tchernia G . Acute autoimmune hemolytic anemia during interferon-alpha therapy for chronic hepatitis C. Dig Dis Sci. 1999; 44(7):1366-7. DOI: 10.1023/a:1026643500569. View

Sevastianos V, Deutsch M, Dourakis S, Manesis E . Pegylated interferon-2b-associated autoimmune thrombocytopenia in a patient with chronic hepatitis C. Am J Gastroenterol. 2003; 98(3):706-7. DOI: 10.1111/j.1572-0241.2003.07315.x. View

Tomita N, Motomura S, Ishigatsubo Y . Interferon-alpha-induced pure red cell aplasia following chronic myelogenous leukemia. Anticancer Drugs. 2001; 12(1):7-8. DOI: 10.1097/00001813-200101000-00002. View

Jacobs L, Cookfair D, Rudick R, Herndon R, Richert J, Salazar A . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996; 39(3):285-94. DOI: 10.1002/ana.410390304. View

Kazuta Y, Watanabe N, Sagawa K, Kobayashi H, Kojima T, Funabashi H . A case of autoimmune hemolytic anemia induced by IFN-beta therapy for type-C chronic hepatitis. Fukushima J Med Sci. 1995; 41(1):43-9. View

Walther E, Hohlfeld R . Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology. 1999; 53(8):1622-7. DOI: 10.1212/wnl.53.8.1622. View

Rotondi M, Mazziotti G, Biondi B, Manganella G, Del Buono A, Montella P . Long-term treatment with interferon-beta therapy for multiple sclerosis and occurrence of Graves' disease. J Endocrinol Invest. 2000; 23(5):321-4. DOI: 10.1007/BF03343730. View

Donato H, Kohan R, Picon A, Rovo A, Rapetti M, Schvartzman G . Alpha-interferon therapy induces improvement of platelet counts in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2002; 23(9):598-603. DOI: 10.1097/00043426-200112000-00009. View

10.

Ernstoff M, Lembersky B, Kirkwood J . Fluorouracil, interferon-alpha, and colon cancer: rational pursuit of synergism between antimetabolites and biologicals. J Clin Oncol. 1989; 7(12):1764-5. DOI: 10.1200/JCO.1989.7.12.1764. View

11.

Panitch H, Goodin D, Francis G, Chang P, Coyle P, OConnor P . Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology. 2002; 59(10):1496-506. DOI: 10.1212/01.wnl.0000034080.43681.da. View

12.

Rajan S, Liebman H . Treatment of hepatitis C related thrombocytopenia with interferon alpha. Am J Hematol. 2002; 68(3):202-9. DOI: 10.1002/ajh.1180. View

13.

Vianelli N, Gugliotta L, Tura S, Bovicelli L, Rizzo N, Gabrielli A . Interferon-alpha 2a treatment in a pregnant woman with essential thrombocythemia. Blood. 1994; 83(3):874-5. View

14.

. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993; 43(4):655-61. DOI: 10.1212/wnl.43.4.655. View

15.

Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O . Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001; 357(9268):1576-82. DOI: 10.1016/s0140-6736(00)04725-5. View

16.

. PRISMS-4: Long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001; 56(12):1628-36. DOI: 10.1212/wnl.56.12.1628. View

17.

Toccaceli F, Rosati S, Scuderi M, Iacomi F, Picconi R, Laghi V . Leukocyte and platelet lowering by some interferon types during viral hepatitis treatment. Hepatogastroenterology. 1998; 45(23):1748-52. View

18.

Sagir A, Wettstein M, Heintges T, Haussinger D . Autoimmune thrombocytopenia induced by PEG-IFN-alpha2b plus ribavirin in hepatitis C. Dig Dis Sci. 2002; 47(3):562-3. DOI: 10.1023/a:1017964002402. View

19.

Dikici B, Bosnak M, Kara I, Dogru O, Alkaya A, Hasolat K . Interferon-alpha therapy in idiopathic thrombocytopenic purpura. Pediatr Int. 2001; 43(6):577-80. DOI: 10.1046/j.1442-200x.2001.01477.x. View

20.

Barel C, Bilger K, Ninet J, Scoazec J, Dumortier J . Treatment of hepatitis C virus-associated thrombocytopenic purpura with a combination of interferon alfa-2b and ribavirin. J Clin Gastroenterol. 2002; 35(2):200-1. DOI: 10.1097/00004836-200208000-00015. View