Neutralising antibodies to interferon-β in the treatment of multiple sclerosis -: Cause for concern?

The recent introduction of several forms of interferon-beta as first-line medication for the treatment of relapsing-remitting multiple sclerosis has opened a new area in the management of the disease. As in most other attempts at treating diseases with biological agents, reports have started to appear that antibodies to the agent can be found in a large proportion of treated patients. To review the clinical significance of these antibodies, we will assess the findings of these studies from a historical and technical perspective. Despite the existence of World Health Organization recommendations for standardisation and exchange of samples, the companies involved have pursued their research efforts entirely independently. At the present time, technical differences between tests, absence of standardisation and 'in-house testing' preclude definitive comparisons. Early reports have used simplistic statistical approaches to evaluate the clinical impact that these antibodies may have on the therapeutic effect of interferons. Out review of the field leads us to conclude that: (i) antibodies appear, but they often disappear if the treatment is continued: (ii) it has not been conclusively demonstrated that the appearance of antibodies is responsible for a reduced efficacy of the treatment (iii) methods for assaying antibodies need to be standardised to allow for meaningful clinical correlations; and (iv) low levels of antibodies probably have no clinical significance, whereas high levels may alter the bioavailability of the drug. We recommend thar regulatory agencies and the companies producing interferons come to an agreement on possible standardisation of the assays through third party involvement and that sera from pivotal trials be made available for such standardisation.