Is multiple sclerosis a disease that requires frequent beta interferon dosing?

The three currently available beta interferon products for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) are administered according to different regimens. Placebo-controlled clinical trials support the efficacy of both alternate-day interferon beta-1b (Betaferon(R)) and once-a-week interferon beta-1a (Avonex(TM)), but benefits to patients are probably dependent on the regimen used. Once-weekly administration, perceived to have fewer adverse events and greater convenience, may improve compliance, whereas frequent administration might enhance efficacy. However, more frequent administration is also associated with an increase in neutralising antibody (NAb) production, relative to once weekly treatment. The issue of NAbs is complex, and their clinical relevance, if any, has yet to be fully assessed. Pharmacological evidence suggests that the effects of beta interferon on a number of biological markers is maximised when administered every 48 hours. This might arise as a result of sustained activity in the intracellular molecular signalling pathways regulating beta interferon-induced gene expression. Some evidence suggests that the increase in biological effect at higher more frequent doses is mirrored by improvements in clinical and MRI outcome measures. Two recent comparative studies demonstrated significantly better clinical and magnetic resonance imaging outcomes in patients with RRMS receiving alternate-day high-dose interferon beta-1b (250 mug subcutaneously) or three-times-weekly high-dose interferon beta-la compared to those receiving once weekly low-dose interferon beta-la (30 mug intramuscularly). Despite some methodological drawbacks, these studies indicate that the benefits of high-dose frequently administered beta interferon on relapse rate are seen soon after beginning treatment. Therefore, it seems appropriate to begin the treatment of RRMS with this dosing regimen.