Early experience and clinical tips for the use of CGRP inhibitors in migraine prevention

14 Oct 2021

With the PBS-listing of calcitonin gene-related peptide (CGRP) inhibitors1,2 for the preventive treatment of chronic migraine (Authority Required – Streamline), neurologists now have wider access to treatments specifically developed for migraine. The limbic spoke to leading Australian headache specialists Dr Bronwyn Jenkins from Sydney and Dr Christina Sun-Edelstein from Melbourne about their experience with CGRP inhibitors and clinical tips on their use.

Experience in patients with refractory, difficult-to-control migraines

There are currently two CGRP inhibitors – galcanezumab (Emgality)3 and fremanezumab (Ajovy)4 – available on the PBS for the prevention of chronic migraine. Chronic migraine is defined as an average of 15 or more headache days per month, with at least 8 days of migraine, over a period of at least 6 months. To meet the criteria for therapy, the patient must have experienced an inadequate response, intolerance or a contraindication to at least three prophylactic migraine medicines, and treatment cannot be used in combination with botulinum toxin.1

With the PBS restrictions, CGRP inhibitors tend to be considered for patients with the most severe chronic migraine, but Dr Jenkins has been surprised that even in this group she’s seen good results. “I initially had low expectations because I was using them in the very refractory, difficult-to-control patients,” she says. “But even in those with daily headache – where many are migrainous, and there’s triptan overuse – I’ve found a significant proportion of responders,” she explains.

Dr Sun-Edelstein runs the headache clinic at St Vincent’s Hospital in Melbourne. She agrees it’s impressive that CGRP inhibitors have often shown good effect in patients refractory to other migraine prevention therapies. “Sometimes it’s believed that with a new medication there will be a high placebo response, but patients who have been particularly refractory and have tried so many things don’t expect very much. So placebo responses in these patients tend to be low. When we see an improvement in this group of patients, it is quite significant,” she says.

Choosing suitable patients for CGRP inhibitors

Any pre-concept of who to select for this medication needs to be put aside – there’s no pretest for a responder,” says Dr Jenkins. “Since there’s no way of telling who is going to respond surprisingly well, it’s good to try it and worth considering in anyone with migrainous headaches that have not responded to other therapies,” she says.

Dr Sun-Edelstein says that CGRP inhibitors sit alongside other preventive therapies as an option for her chronic migraine patients. “From the specialist headache clinic perspective, one of the biggest decisions now is whether to go down the Botox route or the CGRP inhibitor route,” she explains. “The experience with Botox is much longer and more extensive [than that with the CGRP inhibitors] – I’ve been using it for chronic migraine patients for over 15 years and am very comfortable with it and know what to expect from it, and I do find that it is helpful for many patients,” she says.

Dr Sun-Edelstein explains her approach to discussing the choices for preventive therapy to patients: “When I’m speaking to my patients about the choice between Botox and anti-CGRP therapy, the decision often comes down to the practicalities: do they live far away, is it difficult to come in every three months for Botox injections, would they prefer to have something they can administer on their own? Do they prefer something that has a longer record of treatment [as opposed to something new], or are they really keen to try the newest treatment.”

The CGRP inhibitors have provided a welcome option in difficult-to-treat patients for Dr Sun-Edelstein: “In this headache clinic population, we are seeing the most refractory group of patients who have tried Botox and it hasn’t worked, or the effect has waned over time, or they haven’t had as good a response as they’d like. In those situations it’s a fairly straightforward decision offer a CGRP inhibitor [for preventive therapy],” she says. However, she notes that those who are doing well on Botox tend to stick with their current treatment,  and are generally hesitant to “rock the boat” with their preventive therapy.

Documenting baseline headache days: a key component of PBS criteria

Dr Jenkins explains that adequate documentation is required in order to ensure the patient is eligible for PBS-reimbursed therapy. “The migraine days at onset and at three months must be documented in the notes, and this is quite a specific requirement compared to other medications,” she explains. This may mean returning to baseline information about migraine days when the patient was first prescribed a CGRP inhibitor via a private prescription or access scheme before the PBS listing.

Dr Sun-Edelstein finds the specific nature of the PBS listing can be helpful. “There are a lot of factors to consider for preventive therapy. Patients need to have tried or had contraindications to at least three preventive medications and the specific medications are listed in the criteria,” she explains.

The value of migraine diaries

Migraine diaries help document baseline information, provide an indication of the impact of medication, and can act as a tool to help educate patients on the difference between a migraine and a headache. Dr Sun-Edelstein explains that patients can underestimate the number of migraines they experience each month: “The diaries are an essential part of assessing migraine frequency and intake of acute medication. When you ask patients how often they have migraines, they are often only thinking of the ones that are really severe, that cause them to miss work, or ruin their weekend. They’re not recognising that some of their headaches that are moderately severe and associated with light sensitivity/nausea/phonophobia are actually migraines and need to be counted in their migraine days.”

Dr Jenkins agrees that patients have a tendency not to recognise (or count) migraines that don’t cause significant disruption to their lives. “Most of my patients may count their migraines as those worst days when they are vomiting in bed. In my history taking when you ask about their moderate and milder headaches, you actually realise the moderate ones are usually migrainous as well, but the patient doesn’t consider them to be migrainous because they’re not the ones that completely floor them.”

Dr Sun-Edelstein notes, “We don’t want to overstate the number of migraines, but it is worth pointing out to them that not all migraines will leave them feeling “hung over” and washed out the next day.”

Administration options for patients

The CGRP inhibitors are administered by subcutaneous injection. Administration devices include an auto-injector (for Emgality) and a prefilled syringe.

Dr Jenkins explains that patient preference drives the choice between the administration devices: “People with needle phobias tend to prefer the autoinjector, but some people prefer the pre-filled syringe and they control rate, and sometimes they have family member give it to them.”

In terms of administration advice, Dr Jenkins says that she provides a few tips that may not be so obvious to patients who don’t have experience with self-administration of subcutaneous injections. She also guides them towards company-developed patient education materials that are available online.* “The autoinjector itself is very simple, with a twist to unlock it then button to press. There’s an instructional video on the patient website, which I refer the patients to. It’s useful to tell patients to rotate the sites on either sides of the abdomen or thighs and try ice for 20 minutes on the skin to numb the area before injecting. It’s important to tell the patient that the injections need to stay refrigerated until being used, so they should pick it up from the pharmacy just before going home,” she says.

Dr Jenkins has found that most patients have been relatively comfortable with the injections. “It’s just once a month. Very few people have an issue that they couldn’t or wouldn’t give themselves a needle compared to putting up with severe and debilitating migraine,” she explains.

Side effect management tips

Dr Jenkins has seen very few side effects of the CGRP inhibitors in her patients. “Nasal congestion, constipation or injection site reactions are the side effects to tell patients about,” she says. “There may be other side effects we don’t know about yet,” she adds. Studies are ongoing to provide further data on the longer-term safety profile of these medications.

Therapy may need to be discontinued in the case of severe constipation, she explains. However, for milder constipation, a gentle laxative can be used.

Dr Jenkins notes that the long half-life of the CGRP inhibitors is important to consider in women of childbearing age. “I check about whether the patient has active plans pregnancy because the safety in pregnancy is unknown and it has a relatively long half-life – so generally I like them to be off the therapy for five half-lives which is around 5–6 months,” she says.

*Emgality written resources and an instructional video are available at  https://mylilly.com.au/welcome.


This article was sponsored by Eli Lilly Australia Pty Ltd. Any views expressed in the article are those of the experts alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the Emgality (link) full product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician


  1. PBS listing for Emgality. Available at pbs.gov.au
  2. PBS listing for Ajovy. Available at pbs.gov.au
  3. Emgality Australian Product Information https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2019-PI-01545-1&d=20210921172310101
  4. Ajovy Australian Product Information https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2019-PI-01962-1

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