Actually, with a mini-questionnaire consisting of only three questions with a sensitivity of 0.81 and specificity of 0.75, the suspicion of migraine could be concluded, but this would then still have to be verified by a specialist diagnosis. But because no one does this and migraine is usually not considered a serious illness by both patients and doctors, it is largely not treated adequately. Migraine is not a life-threatening disease, “but it is one that reduces the quality of life,” as Prof. Dr. Zaza Katsarava, specialist in neurology at the Evangelical Hospital in Unna, explained and asked Novartis at the NeuroScience update on the occasion of the DGN 2017 in Leipzig: “Either we are a civilized society that accepts the reduction in people's quality of life or not.” Accepted also means: sufficient treated. But that's exactly what doesn't happen in Germany or anywhere else in the world. Antibodies against the calcitonin gene-related peptide (CGRP) or its receptor are currently in clinical development - hence the update from Novartis - which means - according to Prof. Dr. Dr. Stefan Evers from the Department of Neurology at the Lindenbrunn Hospital in Coppenbrügge – “Now for the first time there is the prospect of urgently needed, effective medication developed specifically for the prophylaxis of migraines.”

>> So far, half of those affected use over-the-counter pain relief medications, with the majority of over-the-counter and/or prescription medications only aimed at relieving migraine symptoms after they have already begun. There are certainly preventative therapies that can reduce the number of monthly migraine attacks. However, these therapy options that can be used to prevent migraines were originally developed for other diseases - such as epilepsy and heart disease as well as muscle diseases, anxiety or depression. As Evers explained, the beta blockers propranolol and metoprolol, the calcium antagonist flunarizine and the anticonvulsants valproic acid and topiramate are the first-line drugs for the prophylactic treatment of migraines.
However, since none of these therapeutic agents was specifically developed as a prophylactic against migraines, many patients would complain about insufficient effectiveness and severe side effects. However, since migraine patients react very sensitively to side effects, up to 80 percent of patients stop prophylactic therapy within the first year.
With the sad result that people affected by migraines are severely restricted in both their professional and social lives. In addition, the majority (90 %) of those affected are completely unable to work during a migraine attack and suffer a complete loss of function. Katsarava, who is the vice-president of the European Headache Society and board member of “Lifting the Burden of Headache Worldwide” in his voluntary part-time job: “The fear of losing your job is high because the sick days are piling up.” Some of those affected ( According to Katsarava, 20 % of men and 30 % of women) miss more than 10 percent of their working days due to migraines. “Not only is the quality of life of migraine patients severely impaired, the disease also represents a financial burden on society,” says the pain specialist, who has made it his mission to fight against the “underestimated burden of illness on migraine patients.” .
Among other things, he wrote an editorial together with Timothy J. Steiner in the magazine “Cephalalgia” entitled “Neglected Headache: Ignorance, arrogance or insouciance?”1, in which the study “Low rate of self-awareness and medical recognition of migraine in Germany”2 was responded to. This study by Radtke and Neuhauser described that only 42 % of migraine patients had consulted a doctor in the last 12 months and of these, only 63% were given the corresponding (correct) diagnosis - and this also depends heavily on the level of education!
Is it ignorance? Katsarava and Steiner asked in their editorial, referring to Radtke and colleagues' finding that people with lower levels of education were less likely to be diagnosed and effectively treated than those with better education. Or is it even arrogance? This is Katsarava and Steiner's second question, in which they focus primarily on domestic
Doctors claim that they do not consider headaches to be medically important and that they do not take the time necessary to diagnose migraines, inform patients, give advice and, above all, initiate appropriate treatment. What makes matters worse is that doctors usually only see those affected when the attack is over. Therefore, according to Katsarava, the descriptions of migraine attacks often receive little attention - overall, the disease is considered to be under-diagnosed and under-treated: over 40 % of migraine patients do not receive a confirmed diagnosis. Katsarava and Steiner's conclusion: “The inescapable truth underlying these failures is that the large number of needy patients requires significant resources that are simply not allocated.” Their conclusion: “It boils down to a gross priority mismatch “, for which insouciant society has only itself to blame”, which translated into German means nothing else, that this manifests a misalignment of priorities for which the unconcerned society has itself to blame.
But this is mainly because neither the quality of life nor the economic damage caused by this disease can be precisely assessed. Since around half of those affected use over-the-counter pain relief products, this disease is not on the health insurance companies' priority list, nor do they have data with which health care research could work. For this reason, a total of 8,271 patients with headaches were surveyed in ten EU countries in the Eurolight study3.
The patients named the immediate attacks, interictal impairments and lost time as the most important impairments. Of the migraine patients surveyed in the study, 28 % women and 18 % men stated that they would lose 10 % of their lives due to migraines, as Katsarava explained in his lecture. Patients with chronic migraines or headaches caused by medication overuse even lose 54 % (women surveyed) or 20 % (men surveyed) of their lives.
This is not only due to the migraine itself, but also to the accompanying illnesses. An analysis by the Eurolight project shows that 19.1 % of migraine patients suffer from anxiety, 6.9 % from depression and 5.1 % from both. In this respect, too, patients with chronic migraines or medication overuse suffer significantly more: 38.8 % have anxiety, 16.9 % have depression and 14.4 % have both anxiety and depression. Many of those affected find it particularly depressing that they are not taken seriously - neither by doctors nor by their social environment. According to the pain doctor, one reason for this is that “no one can see when migraine sufferers are lying helpless and in severe pain at home in a darkened room.” As a result, the enormous burden of illness is hardly acknowledged by superiors, work colleagues or friends. In addition, due to this stigmatization, those affected often do not even dare to talk about their illness.
All of this, or at least most of it, could be prevented if there was adequate medication. This is exactly what is now just around the corner, and not only pain specialist Katsarava is full of “excitement that we are finally getting a specific therapy” that is able to reduce the monthly migraine days using CGRP blockers* developed specifically against migraines thus significantly improving the quality of life of many patients. Evers also shares this opinion when he says: “New medications such as antibodies against CGRP or its receptor, which were able to significantly reduce the number of migraine days in clinical studies, could help here.”
Such statements naturally delight pharmaceutical companies such as Novartis (“Erenumab”), Eli Lilly (“Galcanezumab”) and Teva (“Fremanezumab”), each of which will soon bring one of these antibodies onto the market – the first approvals are likely to be forthcoming. It will not be easy to compare the three active ingredients, the respective studies are designed too differently, as a review article by Prof. Dimos Mitsikostas from the Athens Naval and Veterans Hospital, Department of Neurology, and Prof. Uwe Reuter from the Charité Berlin, Clinic for Neurology with Experimental Neurology, shows. The phase III studies sometimes have different regional recruitment focuses, the inclusion criteria also vary and the primary endpoint is not uniform. “Physicians should be aware of this complex study situation when they are confronted with the results of phase III studies on CGRP inhibitors,” emphasizes Dr. Israel-Willner from the Charité working group. Above all, it is important to know the primary endpoint. In addition, attention should be paid to how seriously ill the patients admitted to the respective study were and what type of concomitant medication they were taking at baseline or during the course of the study.
Nevertheless, Prof. Lothar Färber, Medical Director of Novartis Pharma, is pleased that “we can significantly advance the development of this group of substances”, also because the innovative substance class of CGRP blockers has the potential to close the real therapeutic gap in the care of migraine patients. Until then, it will depend on how and whether the IQWiG will recognize the approval studies to be specified in the respective drug dossiers after approval has been granted, and, above all, how the G-BA decision and the subsequent price negotiations will turn out. <<

According to Prof. Dr. Dr. Stefan Evers (Clinic of Neurology at the Lindenbrunn Hospital, Coppenbrügge) “now for the first time has the prospect of urgently needed, effective medications developed specifically for the prophylaxis of migraines.” The messenger substance CGRP appears to play a significant role in the development, maintenance and chronification of migraines. In his opinion, this is supported, among other things, by the fact that increased CGRP levels are measured during a migraine attack, which would then decline again. This refers to “AMG 334”, the first biological anti-CGRP receptor inhibitor whose application for approval was accepted by the FDA and EMA. If approved, Novartis and Amgen will jointly market this active ingredient under the name “Erenumab” in the USA. Amgen has exclusive marketing rights for the substance in Japan and Novartis has exclusive rights to market it in the rest of the world, including Germany. In a predefined sub-analysis of a pivotal phase II study with AMG 334, people with chronic migraine who had tried two or more preventive treatments in the past without success benefited from the substance. In these patients, AMG 334 reduced the average number of migraine days by at least five days to one week per month, depending on the treatment dose (70 mg: -5.4 days, 140 mg: -7 days, placebo: -2.7 days; p < 0.001 for both doses vs. placebo). In addition, this group also had three to four times higher odds of reducing their migraine days by 50 percent or more compared to placebo (70 mg: 35.6 percent, 140 mg: 41.3 percent, placebo: 14.2 percent , p < 0.001 for both doses vs. placebo).