title: Haematological effects of interferon-beta-1a (Rebif) therapy in multiple sclerosis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Würzburg, Germany. p.rieckmann@mail.uni-wuerzburg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Francis
authors.forename: Graham
authors.initials: G
authors.lastname: Wetherill
authors.forename: Enrica
authors.initials: E
authors.lastname: Alteri
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D001772:Blood Cell Count; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a