Interferons and natalizumab for multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which is accompanied by considerable disability and high costs. This report summarises the evidence on effectiveness and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis.The review included systematic reviews and randomised controlled trials (with an observation time of at least one year) in patients with MS which assessed outcome parameters such as progression, exacerbations and adverse effects. An extensive literature search included databases such as MEDLINE, EMBASE, the Cochrane Library and various HTA-databases. Studies were selected according to predefined criteria, their quality was assessed according to criteria defined prospectively, and data were summarised systematically in tables. Cost-effectiveness evaluations were also included.Two systematic reviews and 24 randomised controlled trials of beta-interferon therapy were included, as well as three trials on the effectiveness of natalizumab. A total of 22 cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified.Use of interferon beta-1a or interferon beta-1b after a first demyelinating event led to a reduction of the conversion to definite MS during an observation time of two to three years. In relapsing remitting MS, interferon beta-1a reduced progression. The effects of interferon beta-1b on progression are unclear. Interferon beta-1a and interferon beta-1b reduced in some but not all studies outcomes relating to exacerbations. In direct comparison trials, interferon beta-1b (Betaferon(®) or Betaseron(®)) and interferon beta-1a (Rebif(®), higher dosage of 44 µg three subcutaneous injections per week) proved superior to interferon beta-1a (Avonex(®), 30 µg per week intramuscular) with respect to exacerbation outcomes. For secondary progressive MS, only one of five studies found a reduced progression with interferon beta-1a and only a part of the studies found an improvement with respect to outcomes relating to exacerbations. For primary progressive MS no advantage of therapy with beta-interferons was found with respect to patient-related outcomes. Beta-interferons showed characteristic and frequently occurring adverse effects, including reactions at the injection site and flu-like symptoms. A large proportion of patients stop interferon therapy because of adverse events. The other main reason for stopping therapy is the felt ineffectiveness of the treatment when patients experience a new exacerbation while on treatment. Many patients produce interferon-neutralising antibodies during therapy. The ultimate effect of neutralising antibodies on the efficacy of interferon treatment is unclear.In patients with relapsing remitting (and partially with secondary progressive) MS, treatment with natalizumab led to a reduction of progression and of exacerbation rates. However, a number of cases of progressive multifocal leucoencephalopathy have been reported after natalizumab therapy. These raise serious concerns about patient safety. Reliable data on the long term effectiveness of beta-interferons or natalizumab are not yet available.The absolute cost of interferon therapy is high and the available, international cost-effectiveness analyses indicate a high cost for achieving moderate benefits in quality of life. Further research is needed to provide specific cost-effectiveness estimates for Germany.