Q What are the main prophylactic treatments for migraine ?
A Professor Ashina says that globally , the most common prophylactic agents are beta-blockers but while effective , adherence problems do occur as some patients experience side-effects or are unable to tolerate the drugs . Overall , he believes that beta-blockers can be just as effective as other prophylactic agents but are often limited by side-effects . Other prophylactic agents such as anti-hypertensives and anti-epileptics are also effective but less widely used . But as with beta-blockers , adherence becomes an issue with anti-epileptics due to adverse effects . Professor Ashina also mentioned how Botox is an effective migraine prophylactic agent but is normally reserved for patients with chronic migraine who have failed to respond to other therapies .
Q Can you tell us about some of the recent innovative treatments in migraine ?
A Some of the latest migraine treatments to be introduced are directed against calcitonin gene-related peptide ( CGRP ). As Professor Ashina explained , ‘ CGRP is widely distributed in migraine-specific structures such as the trigeminal nerve , cranial blood vessels and certain other parts of the brain ’. While its physiological role is yet to be clarified , it is known that migraine attacks can be provoked after infusion of the molecule . Similarly , he said , ‘ administration of an anti-CGRP agent can abort or prevent attacks .’.
The original CGRP agents were the gepants that specifically target the CGRP receptor . These oral treatments are used for acute attacks and serve as an alternative to triptans . While not as effective as triptans , Professor Ashina sees the gepants as a useful alternative to the triptans , especially for patients who are either triptan intolerant or for whom triptans are contra-indicated . Nevertheless , overall he considers the gepants to be a third-line treatment option after triptans . Although most gepants are used for acute migraine , some can also be used as prophylactics . Professor Ashina sees this as an interesting concept , especially given that the triptans cannot be used as prophylactics because they induce medication-overuse headache .
Q What about injectable CGRP agents ?
A Currently , there are four monoclonal antibody CGRP drugs , three of which target the CGRP molecule itself and one its receptor . These drugs are available either as intravenous or a subcutaneous formulations . Two are administered on a monthly basis and others are approved for use every 12 weeks or either monthly or quarterly . Although the efficacy endpoint of these agents within clinical trials is normally measured in terms of a reduction in monthly migraine days , Professor Ashina prefers to translate this in clinical practice as the ‘ proportion of patients
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... current treatments have a good level of tolerability and are without serious adverse events , but there will always be room for improvement ... who report at least a 50 % reduction ’ though as he says , ‘ some patients even report a 75 % reduction .’ While these newer agents significantly reduce the frequency of attacks , Professor Ashina cites a further benefit of the drugs in being able to reduce the intensity of attacks which therefore become more manageable for the patient . An added bonus in that patients can then use triptans and may even feel that the triptans are more effective because the attacks are less intense .
Q What would you like to see next in the management of migraine ?
A Professor Ashina feels that the introduction of CGRP agents is an important paradigm shift in the preventative management of migraine because these molecules have a highly specific target . Moreover , he feels that these drugs have elevated the status of migraine to one of a disease and not , as in the past , just a headache . He is excited to see how these treatments might change patients ’ lives and says how as a physician , it is highly rewarding to see patients return to some semblance of normality that was not possible before therapy . Despite the benefit for many patients , he also acknowledges that ‘ about 40 % or sometimes 50 % of patients do not respond ’ to these drugs hence the continued search for novel drug targets , which is an active area of his research .
Q What do you see as the future goals ??
A Professor Ashina believes that the ultimate goal in migraine research is not to provide a cure – he thinks that this is highly unlikely – but to be able to control an attack so that ‘ patients can return to an almost normal life ’. While he thinks that current treatments have a good level of tolerability and are without serious adverse events , there will always be room for improvement . He added that a further consideration is that while the trajectory of an individual ’ s migraines is unpredictable , there is a natural tendency to resolve with advancing age . Consequently , it is worth occasionally stopping preventative therapy to determine whether an individual ’ s migraines have spontaneously resolved . Due to this unpredictability , he described how in his own clinic they have introduced an 18-month stop rule to assess whether or not continued preventative therapy is required .
Professor Ashina is clearly very enthusiastic and motivated in his search for efficacious migraine treatments . One potential molecular target that he is currently working on , is pituitary adenylate cycles-activating peptide ( PACAP ) and he mentions how , just like CGRP , administration of PACAP provokes a migraine attack . With two ongoing trials assessing monoclonal antibodies directed at PACAP , there is hope that , in the near future , many more migraine sufferers will achieve relief of their symptoms and be able to regain some semblance of normality in their lives .