Combination Therapy

One of the interesting questions to emerge in MS therapies in the next few years will be the possibility of using combination therapy to slow down disease progression. This means the use of more than one medication with different mechanisms of actions to attack the disease from different angles. Currently, patients with MS are put on one disease-modifying drug and that is it.  Other fields of medicine would find this approach laughable.  An internist treating hypertension uses many medicines that act at different receptors to lower blood pressure. Patients with AIDs are put on a cocktail of medications, each of which attacks the HIV virus at different points.  Oncologists often use three or four chemotherapy drugs to fight tumors. So why is this approach not used in MS? 

Currently, one of the largest trials of combination therapy is MS is winding down.  It is known as the CombiRx Trial and details about it are available here. Basically, subjects in this study were treated with Avonex alone, Copaxone alone, or a combination of the two.  Hopefully, this will show that the combination of these two medicines is more powerful than either alone. 

However, few patients with MS are begging for more injections, and with the approval of Gilyena and likely several other oral medications in the next few years, these injectable therapies will likely be used less and less often. However, might there be a role for combining the oral medications with the injectable therapies?  Might there be a role to combine any of these medicines with infusions, such as Tysabri?  No one knows.

The CombiRx study may show that combination therapy works for MS, but only for the particular medications studied.  Though it will be very important to show the principle that combination therapy works, no one can say based on this that other combinations of medicines can then be safely and efficaciously combined.  After all, we know that one of the main risk factors for developing PML for patients on Tysabri is prior treatment with immunosuppressant agents.  And it appears that taking medications that affect heart rate in combination with Gilyena is not safe (though it is premature to say this for sure.)

So as usual, we are left with many more questions than answers.  I suspect that certain adventurous neurologists will combine the oral medications and the injectable medications even without solid evidence that this approach works and is safe.  I suspect that other neurologists will resist that approach unless convincing evidence emerges that these combinations are safe and useful.  However such evidence requires massive trials, such as the CombiRx study, that are expensive and time consuming.  Until further evidence emerges, doctors and patients will have to use their best judgment in deciding what to do.  And though treatment options will soon become more complicated for patients, remember that this is a good thing, as patient prior to the approval of Betaseron in 1993 had no options at all.