COMMENTARY

Four New Studies in Neurology

Hans-Christoph Diener, MD, PhD

Disclosures

July 24, 2018

Dear colleagues, I am Christoph Diener, a neurologist from the University Hospital in Essen, and I would like to report today what happened in the scientific field of neurology in the past 4 weeks, which is June 2018.

PFO and Cryptogenic Stroke

I would like to start with the issue of closure of the patent foramen ovale (PFO) in patients with cryptogenic stroke. Recently we saw three large-scale randomized trials which clearly indicated that patients below the age of 60 years with cryptogenic stroke and a large PFO most probably benefit from PFO closure for the prevention of recurrent stroke. All of these studies had an age limit of 60 years.

The Oxford Vascular Study,[1] published in Lancet Neurology, looked at whether there is a higher risk for PFO in patients above the age of 60 years who have had a cryptogenic stroke. The Oxford Vascular Study is a population-based registry, and in 572 patients they did right-to-left shunt identification by transcranial Doppler and the bubble test. They looked at other etiologies, like large-vessel disease and small-vessel disease. They found an odds ratio of 1.9 for a PFO as a possible cause of cryptogenic stroke compared with other etiologies. I think the conclusion is correct that this would warrant more studies in patients above the age of 60 years.

There is now a fourth study which looked at PFO closure in cryptogenic stroke. The DEFENSE-PFO trial[2] was done in Korea and published in the Journal of the American College of Cardiology. They included 120 patients with the mean age of 52 years and they compared PFO closure versus medical treatment. The primary endpoint was a composite of stroke, vascular death, and major bleeding. Six events occurred in the medication group, which correlates to a 2-year event rate of about 13%, and there was no event in the PFO closure group. This means that we now have four studies showing that PFO closure might benefit patients below the age of 60 years.

Recurrent Glioblastoma

A very exciting phase 1 study on the treatment of recurrent glioblastoma was published in the New England Journal of Medicine.[3] The investigators found that a number of these malignant tumors expressed something called poliovirus receptor CD155. In 61 patients with recurrent glioblastoma, they applied locally seven different doses of recombinant nonpathogenic polio-rhinovirus chimera. The majority of patients [experienced] no effect, but 21% of patients survived for more than 36 months, which is remarkable. Further studies have to follow.

Multiple Sclerosis

Let's move to multiple sclerosis (MS). There is a network of MS centers in Italy. In seven of these centers they compared the outcome of patients who were de novo treated with fingolimod versus dimethyl fumarate.[4] They recruited 483 patients receiving fingolimod and 456 receiving dimethyl fumarate, and then they matched the patients. After matching, 257 patients remained in both groups. The endpoint was no evidence of disease activity, and this was identical between fingolimod and dimethyl fumarate.

Migraine

Finally, good news for migraine patients. Erenumab, which is a monoclonal antibody against the calcitonin-gene-related peptide (CGRP) receptor, was approved in the United States and Europe for the prevention of migraine. We now have four antibodies; one is approved (erenumab) and three are undergoing approval (eptinezumab, fremanezumab, and galcanezumab). These monoclonal antibodies have to be given subcutaneously or intravenously once monthly or every 3 months. If we look at the overall evidence, the patients in the episodic migraine studies have between 7 and 8 migraine days per month. The antibody resulted in a 3- to 4-day reduction of migraine days. The responder rate is about 40%-50%, which means these are patients who have at least a 50% reduction in migraine frequency.

If erenumab comes to the market, what are the advantages? First, there is the clear advantage that the drug has almost no side effects. There are no interactions with other preventive therapy. The drug works very quickly within 3 months. When it is given subcutaneously, compliance and adherence are not a major problem. I think the most important advantage is its extremely good tolerability profile.

What is the downside? The downside is cost. We do not know how the reimbursement bodies will react to this. My prediction is that erenumab will be reimbursed for patients with chronic migraines who failed other treatments like topiramate or botulinum toxin-A and for patients with frequent episodic migraine, who most probably failed available treatments. These are exciting times for our patients with migraine.

Ladies and gentlemen, I had news for you regarding PFO and cryptogenic stroke, recurrent glioblastoma, multiple sclerosis, and migraine. I am Christoph Diener from the University Hospital in Essen. Thank you very much for listening and watching.

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