CME/CNE

Optimizing Treatment to Delay Disease Progression and Preserve Cognitive Function: A Review of Established and Emerging Therapies for MS

Rhonda R. Voskuhl, MD

University of California
Los Angeles School of Medicine
Los Angeles, California

The questions below were submitted by your peers based on a recent CME/CNE activity.
The Course Director, Dr. Rhonda R. Voskuhl, provides her answers below.

Question 1: I would appreciate your input on the following scenario: I have a patient, a 45-year-old RH [sic] female with relapsing-remitting MS, who has been on glatiramer acetate for 6 years. She has not had a recent new focal sensory motor deficit. In recent follow-up, I repeated her MRI of brain and spinal cord with and without gadolinium to compare with her most recent prior study 4 years ago. On the repeat study, she has no enhancing lesions nor any new diffusion signal. She does, however, have a lesion in the deep white matter (ie, parietal region, ~5 cm), which was not present in the prior study. Otherwise, there were no new changes. At this time, I don't think I can consider her a glatiramer acetate failure. Of note, the patient is very hesitant about considering interferon therapies due to stated side effects. My plan is to give her a 4-day course of IV methylprednisolone, to follow her neuro status, and to re-image in several months. If, at that time, there is new activity on the repeat MRI, or if she were to have an obvious new event, I would then consider changing her chronic therapy. I'd be curious to have your feedback on this case.

Question 2: What are some of the rational combinations showing promise in MS?

Question 3: Beyond cognitive impairment, which neuropsychiatric disorders should we be looking out for in our patients with MS?

Question 4: Have the new formulations of the existing MS therapies demonstrated superiority to the older agents?

I would appreciate your input on the following scenario: I have a patient, a
45-year-old RH [sic] female with relapsing-remitting MS, who has been on glatiramer acetate for 6 years. She has not had a recent new focal sensory motor deficit. In recent follow-up, I repeated her MRI of brain and spinal cord with and without gadolinium to compare with her most recent prior study 4 years ago. On the repeat study, she has no enhancing lesions nor any new diffusion signal. She does, however, have a lesion in the deep white matter (ie, parietal region, ~5 cm), which was not present in the prior study. Otherwise, there were no new changes. At this time, I don't think I can consider her a glatiramer acetate failure. Of note, the patient is very hesitant about considering interferon therapies due to stated side effects. My plan is to give her a 4-day course of IV methylprednisolone, to follow her neuro status, and to re-image in several months. If, at that time, there is new activity on the repeat MRI, or if she were to have an obvious new event, I would then consider changing her chronic therapy. I'd be curious to have your feedback on this case.

It sounds like this patient is experiencing no clinical relapses and is not progressing. One new lesion in deep white matter is not grounds for failure. She is a glatimer success and should be kept on it.

What are some of the rational combinations showing promise in MS?

Not many combinations have been tested rigorously. They require very large sample sizes because each works independently, thus making it hard to demonstrate benefit over something that already works as a single agent. The most well known combination study ongoing is a randomized, multicenter phase 3 trial that combines glatiramer acetate and interferon (IFN) β-1a in relapsing-remitting MS (www.clinicaltrials.gov/ct2/show/NCT00211887. Accessed March 29, 2010).

Beyond cognitive impairment, which neuropsychiatric disorders should we be looking out for in our patients with MS?

Depression is common among patients with MS. Of note, treatment with the interferons may proliferate and/or intensify depressive symptoms.

Have the new formulations of the existing MS therapies demonstrated superiority to the older agents?

Newer agents have not yet been shown to be superior in large, rigorous studies. However, investigators on the EVIDENCE study found IFN β-1a 44 μg given subcutaneously TIW to be more effective than IFN β-1a 30 μg given intramuscularly QW in reducing brain lesion activity on MRI and preventing relapses at 48 weeks (Schwid SR, Panitch HS. Clin Ther. 2007;29:2031-2048).

It is not clear if this is due to the more frequent and higher dosing of SC IFN β-1a or the difference in route of administration.