There have been no conclusive studies of interferon beta in PPMS; preliminary data suggests that the (small) potential impact is outweighed by side-effects.

Another important consideration is the propensity for IFN beta to stimulate the formation of neutralising antibodies (NABs), which might depend on a number of variables, including a dose-administered (greater risk with the lower dose of sc IFN beta-1a) route of administration (lower risk for IM versus sc route), frequency of administration (lower risk with once-weekly administration), and type of IFN beta used. A number of studies suggest that the rate of NAB formation seems to be less in the IFN beta-1a trials (5–20 percent as compared with 25 –35 percent for IFN beta-1b), but the fact that different assays were used in some of these studies must be taken into account. Laboratory research has clearly shown that NABs suppress the biological activity of the interferon administered; there are also reports that the development of NABs is associated with reduced effectiveness (relapse rate reduction), especially if NABs are present in high titers. This remains a great concern, but it seems that with time antibody levels may disappear in at least a proportion of the patients. Some experts recommend that the presence of high titer NABs should lead to discontinuation of treatment, whereas others think that there is still insufficient information on the utilisation of assays for NAB-testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cut-off titer to apply.

The cost of therapy, currently at least the equivalent of U.S. $10,000, requires a careful cost-benefit analysis. Few studies have addressed the question of whether treatment ideally should be discontinued at some point. Present guidelines for stopping therapy are related to side effects, a desire to become pregnant, and perceived inefficacy as documented by relapses or progression of disability. A recent report suggests that both clinical relapses during treatment with IFN beta and new MRI lesion activity correlate with poor response to treatment.

Clarifying the mechanism of action also is of great importance, not only because it could guide further research with respect to other treatment modalities that could be used (alone or in combination with IFN beta), but also because it might allow discrimination between those patients who are likely to respond to the drug and those who are not. Interferons inhibit T-lymphocyte and monocyte activation and proliferation, reduce IFN gamma and MHC-II expression, increase IL-10 production, down-regulate antigen presentation, reduce lymphocyte migration and blood–brain barrier permeability, and alter the body’s response to viral infections.

In the opinion of the Committee, treatment with interferon beta should be recommended for patients with active relapsing disease. At this time it is not possible to decide which, if any, of the interferon beta preparations should be preferred. There is some indication that more frequent and higher-dosed interferon beta has superior efficacy, but for some patients once weekly intramuscular administration seems to be better tolerated. For patients in the (secondary) progressive phase of the disease, the recommendation to initiate treatment is much weaker. The relatively negative results of three of the four pivotal trials in secondary progressive MS suggest that this class of treatment likely has little meaningful effect in slowing clinical disability in this cohort of patients.