Treatment recommendations for interferon-â in multiple sclerosis

Interferons (IFNs), first recognised because of their antiviral properties, are a key defence mechanism involved in the control of virus infections. They are small proteins separated by nucleated cells in response to viral infection or other appropriate stimuli, and are thought to act principally on other cells in their immediate vicinity. They are divided into two types: type 1 comprises IFN-á and IFN-â, whereas type 2 is IFN-ã. Initially IFNs were considered for the treatment of multiple sclerosis in the context of presumed viral pathogenesis. Because there was some evidence for a decrease in the concentration of IFN-ã in the CSF of patients with multiple sclerosis, a pilot study was performed to assess its safety and eYcacy. This trial was prematurely terminated because of an unexpected increase in relapse rate. This adverse result focused attention on the eVects of type 1 IFNs because they were found to have some immunomodulatory eVects that were opposite to those of IFN-ã. IFN-á and IFN-â use the same receptor, have comparable eVects, and a high degree of homology. Some smaller studies suggested eYcacy for intrathecally, subcutaneously, and intramuscularly administered type 1 IFN in decreasing the frequency of exacerbations in relapsing-remitting multiple sclerosis. Therefore, further studies were performed: subsequently the availability of recombinant IFN led to the abandonment of natural IFN. Research programmes, started over a decade ago, have now resulted in the regulatory approval (in the USA, Europe, or both) of three preparations of IFN-â, these being, in alphabetical order, R/Avonex (IFN-â-1a produced by Biogen), R/Betaseron/Betaferon (IFN-â-1b produced by Berlex/Schering), and R/Rebif (IFN-â-1a produced by Ares Serono). The clinical evidence that has led to regulatory approval and the scientific debate surrounding it is reviewed here. It is important to realise that it is diYcult to compare the various preparations. Their specific activity diVers (higher for IFN-â-1a than for IFN-â-1b) and there is considerable controversy about the eVects of diVerent routes of administration and diVerent dosage schedules on the biological eVects of IFN-â.