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

The recent introduction of several forms of interferon-beta as first-line m edication for the treatment of relapsing-remitting multiple sclerosis has o pened a new area in the management of the disease. As in most other attempt s at treating diseases with biological agents, reports have started to appe ar that antibodies to the agent can be found in a large proportion of treat ed patients. To review the clinical significance of these antibodies, we wi ll assess the findings of these studies from a historical and technical per spective. Despite the existence of World Health Organization recommendations for stan dardisation and exchange of samples, the companies involved have pursued th eir research efforts entirely independently. At the present time, technical differences between tests, absence of standardisation and 'in-house testin g' preclude definitive comparisons. Early reports have used simplistic stat istical approaches to evaluate the clinical impact that these antibodies ma y have on the therapeutic effect of interferons. Out review of the field leads us to conclude that: (i) antibodies appear, b ut 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 antibod ies need to be standardised to allow for meaningful clinical correlations; and (iv) low levels of antibodies probably have no clinical significance, w hereas high levels may alter the bioavailability of the drug. We recommend thar regulatory agencies and the companies producing interfero ns come to an agreement on possible standardisation of the assays through t hird party involvement and that sera from pivotal trials be made available for such standardisation.