A switch to a second-line drug in a patient receiving first-line therapies likely will be effective at decreasing disease activity.
A common referral question for patients being sent to a specialty multiple sclerosis (MS) clinic is what therapeutic decisions to make when a patient continues to have relapses despite having received treatment with Copaxone or interferons.
Despite the relative effectiveness of these first-line drugs, there are certainly patients who continue to have active disease and it is important to consider switching them to a second-line therapy in a timely manner. In the main, this therapeutic decision has been based on discussing the various available therapies with patients and considering the route of administration and potential adverse effects before making a decision. However, a new study published in the Annals of Neurology1 has provided the beginnings of some useful efficacy data to help guide this decision.
The design of the study was to use a large cohort of prospectively followed MS patients with many details of therapy and clinical activity followed. The authors culled out patients who were switched to either Tysabri or Gilenya from first-line therapy because of persistently high disease activity. They then compared the disease activity in the 6 months prior to switching with the 12 months after switching to try to extract information as to which of the therapeutic switches was more effective. The authors ended up with a sizable group of 578 patients (407 switched to Tysabri and 171 to Gilenya).
Although the authors concluded from their analysis that Tysabri is slightly superior to Gilenya on the basis of efficacy in decreasing both disease activity and short-term disability, what really struck me was the dramatic efficacy of both agents after switching. It is important to remember that this is a group of patients who were already on disease modifying therapies and that these patients had dramatic response to changing to one of the second-line therapies.
I don’t believe the differences between Tysabri and Gilenya in this study are great enough to outweigh a variety of other considerations that go into what agent to use for a switch. Patients with +JC virus titers are unlikely to move to Tysabri unless there is no other choice. Also, this study didn’t include switches to Tecfidera, which might have been similarly effective.
In the end, though, I believe the major message here is that a switch to a second-line drug in a patient with active RRMS on first-line therapies is quite likely to be extremely effective at decreasing disease activity.
1. Kalincik T, Horakova D, Spelman T, et al. Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol. 2015;77:425-435.