Nonresponse to Disease-modifying Therapies for Multiple Sclerosis

In discussing nonresponse to multiple sclerosis (MS) treatment, the panelists describe how they assess the need to switch a patient with breakthrough MS disease activity to an agent with a different mechanism of action.

Patricia K. Coyle, MD, says she particularly looks for clinical attack relapses, worsening neurological exam results, and new lesions on magnetic resonance imaging (MRI) scans, which would all suggest breakthrough disease activity and, consequently, nonresponse to treatment.

“You don’t want to sit on a patient having breakthrough unacceptable disease activity. You really want to get the patient on a treatment that they’re tolerating (and that) is safe for them, but really minimizes any breakthrough disease activity,” Coyle explains.

Before making the decision to switch to a different disease-modifying therapy, Clyde E. Markowitz, MD, typically performs an MRI scan at baseline and the 6-month mark within the first year of initial treatment “to kind of get a sense of whether you think somebody’s adequately being controlled on an agent.”

In the particular case of injectable interferon beta therapy, “there are pretty consistent data from various studies showing that breakthrough disease — meaning a new lesion appearing on an MRI scan at 6 months — is actually predictive of a worse outcome,” Andrew D. Goodman, MD, FAAN, says. Nevertheless, “whether or not that’s enough to prompt a change in therapy in somebody who’s feeling quite well and is acclimated well to the therapy is still a tough clinical decision,” Goodman notes.

“If there’s one new asymptomatic lesion, we might keep them on the same therapy and scan again in 6 months. On the other hand, if there’s symptoms (and) more than one lesion, that generally is going to prompt a real serious consideration about changing therapy — even 6 months in,” Goodman advises.