We are entering a new period in MS therapy over the next several years. With a variety of drugs acting through different mechanisms now approved for MS, it is now time to consider whether there is a case for rational polytherapy for MS. In a sense we have been using polytherapy for some time by combining the use of steroids for flares with the approved disease-modifying therapies. It seems likely though that a variety of trials will be appearing over the next few years examining the efficacy and safety of combinations of therapies for MS.
In this context the recent appearance of a clinical trial of combination therapy using glatiramer acetate (Copaxone) and interferon (Avonex) therapy provides some useful insights (Lublin et al., March 2013 Annals of Neurology). First, and most importantly, there was no clear clinical benefit of the combination therapy over single therapy with either agent. This is a bit disappointing of course but there are some brighter points. Although there wasn't a clear clinical benefit, a modest effect on radiologic outcome was detected. It remains possible that a longer followup would yield some evidence of clinical benefit, but this remains unknown. This potential radiologic benefit is interesting but may underlie one of the problems with combination therapy trials. The individual agents are quite good at decreasing radiologic progression in a large fraction of patients, thus demonstrating clinical benefits in combination therapy trials is likely to require longer and bigger trials. This is a problem since there isn't much benefit to the drug makers in supporting combination trials and these efforts are likely to be more dependent on NIH funding at a time when that support is shrinking.
Another consideration is that all current approved therapies work via immunomodulation or suppression. This may mean that the benefits of combination therapy are always going to be modest. What is needed is a class of therapies directed at improving repair or decreasing neuronal toxicity in MS. These types of therapies are very likely to be helpful in combination with therapy to slow down the immune response to myelin.