Introduction: Interferon-β-Abstract-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-β-1a (Rebif®) allows a comprehensive, retrospective assessment of both common and infrequent haematological effects associated with interferon-β therapy.
Methods: Haematological laboratory abnormalities were analysed from six randomised, controlled clinical trials of subcutaneous interferon-β-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-β-1a doses ranged from 22μg once weekly to 44μg three times weekly. Postmarketing surveillance data were also analysed.
Results: Treatment with interferon-β-1a led to asymptomatic dose-related reductions in all cell lineages under investigation, predominantly white blood cells. The greatest differences between interferon-β-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-β-1a, 44μg 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-β-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-β-1a therapy.
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The authors wish to express thanks to the patients who have participated in the studies, contributing data to this analysis and to the physicians and other study site personnel responsible for their care. Studies from which data have been utilised include PRISMS, SPECTRIMS, ETOMS, OWIMS, Nordic SPMS and EVIDENCE. Sarah-Jane Blake, Caudex Medical Ltd, provided valuable manuscript assistance.
Drs Rieckmann and O’Connor have received funding for research activities and honoraria for lectures and advisory panels from the manufacturer of Rebif®; Drs Francis and Alteri are employees of Serono; Dr Wetherill provided consultant statistical input to Serono.
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