COMMENTARY

Updates in Stroke, Alzheimer's, Headache, and MS

Hans-Christoph Diener, MD, PhD

Disclosures

March 09, 2018

Dear colleagues, I am Christoph Diener, a neurologist from the University of Essen in Germany. I would like to summarize the most exciting publications in neurology research from the past month.

Lack of Progress in Alzheimer Disease

Let me start with the most impressive, which dealt with Alzheimer disease (AD). The New England Journal of Medicine published a large phase-3 study of solanezumab, a humanized antibody against amyloid-beta, for mild dementia. This study recruited 2129 patients with mild AD, as identified by amyloid PET or positive test in the cerebrospinal fluid, who were treated with the antibody or placebo. The study was totally negative for all endpoints.[1]

The second publication[2] shared results from three randomized clinical studies done with the selective 5-hydroxytryptamine-6 receptor antagonist idalopirdine. This drug had shown some promise in combination with cholinesterase inhibitors in a phase 2 study.[3] However, the three trials with 2525 patients with mild-to-moderate AD could not show an impact of the new drug on cognitive decline over 24 weeks. This study was supported by Lundbeck, idalopirdine's co-manufacturer.

The consequence of these negative trials is that one large player in the field, Pfizer, has pulled out of AD research. I predict that Lilly will do the same.

New Data in Stroke

There was a spectacular paper in the BMJ,[4] in which the authors looked at the relationship between smoking and stroke. For their meta-analysis, they identified 55 publications containing 141 cohort studies. They found that compared with nonsmokers, smoking just one cigarette per day increases the risk for stroke by 25% for men and by 31% for women. For comparison, if a man smokes 20 cigarettes per day, the relative risk increases 64%, and for a woman it is 216%. This is very important because it clearly tells our patients that it is not good enough to reduce smoking—you have to quit entirely.

Results from the DEFUSE 3 study were just published in the New England Journal of Medicine.[5] This study compared thrombectomy against standard of care in a time window of 6 to 16 hours after onset of symptoms with CT or MRI perfusion imaging. The study was terminated after 182 patients were randomized, because it was clearly positive. The odds ratio for the modified Rankin scale at 90 days in favor of thrombectomy was 2.77. A good outcome of functional independence, as defined by a score of 0 to 2 on the modified Rankin scale, also favored thrombectomy (45% vs 17%). There was no difference in mortality and a high recanalization rate.

DEFUSE 3 basically replicates what was recently shown in the DAWN study,[6] which had a time window between 6 and 24 hours. I think it is now established beyond any doubt that thrombectomy, together with the proof that penumbra exists, really works up to 24 hours.

There is also an important paper in the recent issue of Stroke.[7] It is the 2018 guidelines for the early management of patients with acute ischemic stroke, from the American Heart Association and the American Stroke Association.

New Headache Classification

The International Headache Society published a new classification of headache disorders in the first edition of Cephalalgia in 2018.[8] There was a preliminary version of this published 3 years ago, but these have since been field-tested and the final version is worthwhile to read.

Treatment Advice for Multiple Sclerosis

The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology published recent guidelines on the treatment of multiple sclerosis (MS) in the European Journal of Neurology.[9] They recommend that disease-modifying drugs should only be used in centers with an adequate infrastructure to talk to patients, provide whatever medication is chosen, and take care of all of the safety measures. In patients with clinically isolated syndrome and positive MRI, they recommend starting with interferon or glatiramer acetate. They say that we should offer early treatments in patients with relapsing-remitting MS. The choice of the disease-modifying drug depends on the patient, disease severity, safety issues, and imaging. They add that we should consider ocrelizumab in primary progressive MS and beta interferon for secondary progressive MS.

Then there was an interesting study published in JAMA Neurology,[10] in which researchers looked at rituximab and other treatments of relapsing-remitting MS in patients identified from the Sweden Multiple Sclerosis Registry. Among 494 patients with MS, 43% took injectable disease-modifying drugs, 4% received fumarate, 10% fingolimod, 24% natalizumab, and 24% rituximab. They found the highest retention over time for rituximab. Only 3% of patients dropped the treatment, compared with 29%-53% with the other treatments. There was a trend for better efficacy for rituximab over the other treatments.

I am totally aware that this is off-label treatment, but I think it should be considered in some patients, in particular when the drug comes off patent and gets much cheaper.

Conclusion

Ladies and gentlemen, these are exciting times. We have again, unfortunately, negative results from AD trials, and I am worried about my uncertainty over whether the industry is willing to stay in this disease. However, we also have a positive trial for thrombectomy in an extended time window, as well as new recommendations for how to treat patients with MS from ECTRIMS and the European Academy of Neurology.

I am Christoph Diener, a neurologist from the University of Essen in Germany. Thank you for watching and listening.

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