Haematological effects of interferon-beta-1a (Rebif) therapy in multiple sclerosis

Drug Saf. 2004;27(10):745-56. doi: 10.2165/00002018-200427100-00005.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects*
  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Agranulocytosis / chemically induced
  • Anemia / chemically induced
  • Blood Cell Count
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Female
  • Hematologic Diseases / chemically induced*
  • Humans
  • Interferon beta-1a
  • Interferon-beta / administration & dosage
  • Interferon-beta / adverse effects*
  • Interferon-beta / therapeutic use
  • Lymphopenia / chemically induced
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Product Surveillance, Postmarketing
  • Retrospective Studies
  • Thrombocytopenia / chemically induced


  • Adjuvants, Immunologic
  • Interferon-beta
  • Interferon beta-1a