New Findings in Parkinson's, Myasthenia Gravis, and Multiple Sclerosis

Hans-Christoph Diener, MD, PhD


March 20, 2019

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener, a neurologist from the Faculty of Medicine at the University of Duisburg-Essen in Germany. I found five interesting studies from neurology, which were published in February 2019.

Let me start with Parkinson's disease. There has been an ongoing discussion for more than 30 years now about whether levodopa is neuroprotective or neurotoxic. We have evidence for both hypotheses from animal experiments. This was now investigated in the so-called LEAP study, which was published in the New England Journal of Medicine.[1]

In this study, 445 people with early Parkinson's disease were randomized to initial therapy with levodopa and carbidopa for 40 weeks compared with placebo. After 40 weeks, all patients received active therapy for another 40 weeks. The primary endpoint was the total score of the Unified Parkinson's Disease Rating Scale (UPDRS).

After 80 weeks, there was no difference in the severity of Parkinson's disease, disease progression, dyskinesia, or fluctuation of motor response. I think this is a very good study because it shows that levodopa is neither neuroprotective nor neurotoxic. This means that if a patient has symptoms severe enough to impair his or her quality of life, one should start with levodopa or dopaminergic drugs.

The second study was published in Brain and it was designed to investigate the local application of glial cell line-derived neurotrophic factor (GDNF) in patients with advanced Parkinson's disease.[2] These patients underwent implantation of a transcutaneous drug delivery device and they received GDNF every 4 weeks for 40 weeks. The study had 41 patients.

Overall, there was no benefit for the change in UPDRS-III in the off state of the patients, but in a post-hoc analysis, nine patients showed a large clinical improvement. This is a very demanding therapy, so I have my doubts about whether this will ever be practical for patients with advanced Parkinson's disease. If we consider deep brain stimulation, it would be a very good option.

The third study deals with myasthenia gravis and was published in Lancet Neurology.[3] Some years ago, this study reported 3-year follow-up outcomes. This was a randomized study in patients with myasthenia gravis without thymoma, where thymectomy blast prednisone was compared with prednisone alone. The combination therapy was clearly superior to medical therapy alone.

A total of 111 patients completed the 3-year follow-up and 68 patients completed the 5-year follow-up. The primary endpoint was the Quantitative Myasthenia Gravis score, which was significantly low after 5 years in patients who received surgery blast prednisone compared with prednisone alone. The combination group needed about 50% less prednisone as a long-term therapy compared with monotherapy. I think this shows that the combination is superior to medical therapy alone; however, the numbers for long-term evaluation were low.

The last two studies deal with multiple sclerosis (MS). The first study was designed to evaluate the progression of relapsing-remitting MS to secondary progressive MS over a period of about 10 years and was published in JAMA.[4] Half of the patients with relapsing-remitting MS will get secondary progressive MS; however, after 20 years, it's almost 80% of all patients.

This was a cohort study from 68 MS centers in 21 countries, with a total of 1555 patients. The investigators compared initial treatment of beta interferon and glatiramer acetate with no treatment, and with a more aggressive therapy combination of fingolimod, natalizumab, and alemtuzumab.

Patients treated with beta interferon or glatiramer acetate had a 30% lower risk of progressing from relapsing-remitting MS to secondary progressive MS than did untreated patients. Patients receiving second-generation therapy had a 40%-60% lower risk for conversion to secondary progressive MS. I think this is a strong argument to initiate more aggressive therapy early on; however, it is important to consider that these therapies have more serious adverse events. There must be a discussion with the patient, considering benefits and potential risks of therapy.

The last study, also published in JAMA, was designed to assess patients with relapsing-remitting MS who had a poor response to treatment.[5] These 110 patients were randomized to nonmyeloablative hematopoietic stem cell transplantation with continued disease-modifying therapy. The endpoint was progression measured using the Expanded Disability Status Scale (EDSS) after 1 year. The study randomized 98 patients. Progression after 1 year was reported in three patients in the transplantation group compared with 34 patients in the standard therapy group. The EDSS decreased in the transplantation group and increased in the control group.

Fortunately, there were no deaths or serious adverse events. Hematopoietic stem cell transplantation is an invasive therapy that carries considerable risk. For patients who do not respond to disease-modifying therapies, this is a viable option in the hands of physicians in specialized centers who know the benefits and risks of this procedure.

Ladies and gentlemen, I have discussed five interesting studies published in February 2019. I am Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany. Thank you very much for listening and watching.

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