CGRP and other headache treatments: ANZHS meeting highlights with Associate Professor Richard Stark


By Mardi Chapman

16 Mar 2021

ANZHS president Associate Professor Richard Stark

The Australian and New Zealand Headache Society (ANZHS) held their ASM over the weekend of 13-14 March. It featured an “all star cast” of international and local speakers. ANZHS president Associate Professor Richard Stark shared some highlights with the limbic.

What’s new? CGRP inhibitors

Data was presented on the TGA approved CGRP antibodies – Aimovig, Ajovy and Emgality – and a fourth infusional antibody from Lundbeck which is not yet approved in Australia.

“All of them are clearly effective. All of them seem to have a pretty benign side effect profile,” Associate Professor Stark said.

However a couple of issues have arisen with increasing real world experience of the drugs, especially in the US.

“They include a tendency for some patients to develop hypertension or to have hypertension exacerbated but it seems to be pretty uncommon and at a low level. The message was, if using these agents, it’s not a bad idea to check blood pressure occasionally.”

“There are some rare anecdotal reports of inflammatory conditions that seem to flare up soon after the injections have been given. And obviously it’s hard to know if that is chance or whether there is a connection. Obviously these are things we will be looking at to see what registries in the future reveal.”

“I guess the other thing about the CGRP antibodies is whether they will have a place in treating cluster headache which is obviously less common than migraine but is a big problem for patients who have it. There is some suggestion at least that the CRGP antibodies may be helpful for patients with episodic cluster and possibly for chronic cluster as well although the trials haven’t been quite so definitive for that.”

What about the kids?

“One of the things that was discussed is the difficulty we always face with these new drugs is the trial populations are always very restricted. So for example, they never include children. They never include for obvious reasons pregnant women, and there are a number of other restrictions as well. So it becomes a major practical issue as to how one manages patients who have fallen outside those trial parameters.”

He said there was no suggestion the CGRP inhibitors would work any less well in children but no one has yet done the studies.

“What we need to do is demonstrate that they are safe and effective in adults, demonstrate there aren’t any theoretical reasons why there should be a problem in children, and then run a study in children.”

He noted that industry may not be interested in running another expensive trial which would probably not expand their market a great deal.

Waiting for gepants and ditans

Associate Professor Stark said the small molecules agents were in various stages of roll out overseas. Gepants would clearly have a role in the acute treatment of migraine and may also have a role in preventive treatment of migraine.

“Again we are waiting for them to go through the system and become approved and licensed for use.”

“The ditans are 5HT-1F receptor agonists so they are in some ways similar to the triptans but are thought not to carry the theoretical vasoconstrictor properties of the triptans and so therefore might be more suitable for people with active coronary disease where triptans are not recommended at present.”

Devices make a comeback

Associate Professor Stark said gammaCore, a transcutaneous vagus nerve stimulator recently TGA approved for the treatment and/or prevention of migraine and cluster headaches in adults, was also of interest.

“A lot of the medications that we use are not ideal for everyone. For example, a lot of the migraine preventive medications drop blood pressure, so if you have someone starting with low blood pressure, they are not ideal. Some of them increase appetite so if you are overweight, they are not ideal. Some of them at high doses have got cognitive type side effects so people are nervous about those.”

“While it’s true that we can usually find a preventive medication that is suitable for most patients, there are limitations on some of them. For example in pregnant patients there are very few of the preventive medications that are suitable and so in that situation, devices…are very attractive.”

Personalised and practical prescribing

Associate Professor Stark said there was a whole range of issues to consider when individualising treatment for patients.

“There are probably a dozen preventative medications that are effective in dealing with migraine but all of them have their own pluses and minuses. So you need to look at the patients and if they are someone who is hypertensive, then you are likely to choose one of the medications that will drop their blood pressure. If you have someone who is underweight, you are not going to be inhibited about using medication that might increase their appetite. If you have got someone who has got asthma, you are not going to use a beta blocker.”

“That’s not new but it is something that’s important that we are certainly keen to disseminate among younger neurologists and trainees.”

He said younger colleagues also tended to be very focused on what is on the PBS and don’t recognise that drugs that are not on the PBS can still be prescribed, often without enormous expense.

“Again, it’s knowing what the costs of medications are, whether they are likely to be affordable if they are not on a PBS prescription, and also understanding the patient’s individual position as to what would be financially disadvantageous for them.”

He noted that a lot of medications used for migraine prevention were also not specifically approved for treatment of migraine and there was little financial advantage for pharma to go through the process.

“An example would be candesartan for which there is now very good evidence that it is a highly effective migraine preventive medication but of course its history is as an antihypertensive. It’s available on prescription without any particular restrictions. You can prescribe it for migraine.”

Associate Professor Stark said one component of a successful patient-doctor relationship was making sure it was a partnership with similar and realistic goals.

“Often patients come in with unrealistic pessimism if they have been dealing with migraine for years and years and nothing has ever worked. Others come in unrealistically optimistic having read about medical cures in the press. So it’s important they do have realistic goals.”

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