Migraine preventives exciting but warrant conscientious prescribing

Migraine preventives are offering patients “significant hope” for improved pain and quality of life outcomes, but Australian neurologists are urging clinicians not to get ahead of themselves when prescribing.

A review of the country’s current migraine management options highlighted the importance of, and access routes to, everything from NSAIDs and triptans to preventives such as onabotulinumtoxin A and the latest calcitonin gene-related peptide (CGRP) monoclonal antibodies.

While newer therapies have generated buzz for their efficacy, improved tolerability and simpler treatment regimens, they’re expensive, have limited PBS-support and Sydney-based neurologists are concerned a rush to prescribe them over more cost-effective drugs and lifestyle measures could block subsidised access for patients who could benefit most.

To date, only one-third of migraine patients have been diagnosed and two-thirds were never prescribed a triptan, the review, published in Internal Medicine Journal noted.

It comes despite recommendations that triptans should be used after or in combination with NSAIDs where the latter is “reliably ineffective or poorly tolerated” when tried “a handful of times across different attacks”.

“A simple rule of thumb pertaining to acute migraine management is to trial a number of options such as NSAIDs ±  triptan ± an antiemetic,” review authors, Dr Michael Eller, neurologist at Monash Neurology and Dr Shuli Cheng, neurologist at Alfred Health, Melbourne wrote.

Therapeutics in each class should be “explored systematically” and applied “as early in an attack as possible, preferably within 30 minutes of onset”, they said.

“When occasional headaches are very severe, leading to frequent hospital presentations, time off work, or difficulty in caring for family members, a preventive should be considered”, they wrote.

These include propranolol, sodium valproate and other oral therapies, onabotulinumtoxin A, and CGRP monoclonal antibodies.  The new class of ‘gepant’ small CGRP blockers will also offer preventive benefit for people with migraine, according to Dr Ruaridh Cameron Smail, neurologist at Sydney North Neurology and Neurophysiology and Dr Karl Ng, conjoint associate professor at the Northern Clinical School, University of Sydney, and senior staff specialist neurologist at the Royal North Shore Hospital, in their accompanying editorial.

CGRP-inhibitors in migraine

CGRP inhibitors’ fast action, “relatively minor” side-effect profile, self-administrability (versus onabotulinumtoxin A), and in some cases (galcanezumab and fremanezuma), PBS subsidisation have made them an exciting option for prescribers and patients, the authors say.

Indeed, the drugs have shown therapeutic benefits within three months of use, and in a study of erenumab, in under a week.

However, they’re expensive, have a “wide variation in response, and we are some way from a personalised migraine therapeutic regimen, since CGRP is a poor biomarker candidate, owing to low peripheral blood levels and short half-life”, the commentary read.

There are also concerns about CGRP monoclonal antibody-related vasoconstriction, which could lead to hypertension, though these have not been realised “even in a coronary disease population”, the review and commentary authors discussed.

Finally, to access galcanezumab and fremanezumab via the PBS, chronic migraine patients must have “failed, not-tolerated or have contraindications to at least three preventive migraine medications”, the review said.

Aside from being PBS prerequisites, older therapies still have an important role to play, the review and commentary suggested.

The role non-CGRP inhibitors

“For most migraine sufferers, simple interventions will be adequate,” the review advised.

In fact, some non-responders to newer therapies have gone back to oral preventives “with success”, it noted.

They do typically need to be titrated and used at a target dose for at least six to eight weeks before users will have an adequate sense of efficacy, but can help reduce monthly migraine days, migraine intensity, and the frequency of acute treatment-use, while supporting better acute-treatment response.

Time to perceived benefit, efficacy and side-effects can affect patient adherence and these should all be considered when choosing individuals’ treatments.

Onabotulinumtoxin A also remains an effective, well-tolerated treatment, with an “excellent” safety profile, no drug-drug interactions and PBS access for chronic migraine patients who have failed or can’t tolerate three migraine preventives and can show they aren’t overusing, or have a strategy to address overuse of, opioids.

But high costs, a need to get the injections every 12 weeks and limited access to neurologists or treating public hospital clinics can block treatment.

Accessibility-wise, CGRP inhibitors look more attractive, yet Smail and Ng say clinicians shouldn’t be too quick to prescribe these new drugs — privately or through the PBS.

Conscientious prescribing 

However the authors warned that with migraine such a common and underdiagnosed problem, and without an objective biomarker, the use of these therapies may grow much more than expected, quickly consuming government-subsidised medications and potentially exposing patients and the government to unnecessarily high-costs.

“A similar issue occurred following the licensing of botulinum toxin for use in chronic migraine, where PBS forecasting underestimated the ongoing use of this therapy, resulting in a significant burden of cost on the state and therefore the taxpayer,” they wrote.

Such issues may prevent other medications, like erenumab, achieving PBS listing and ultimately, dam therapy access for patients who could best benefit.

“We must be diligent in ensuring that the treatments we prescribe and administer to our patients are the ones that are most likely to be clinically effective as well as cost-effective,” they advised.

“In the field of migraine, this includes simple, evidence-based lifestyle measures such as dietary, sleep and exercise advice, avoidance of smoking and excessive alcohol, as well as appropriate pharmaceutical treatment, including measures to avoid medication-overuse headache.”

While there’s much to consider around migraine treatment, “the development of rationally designed migraine preventives is the most significant advance in treatment since the development of the triptans and delivers significant hope to many headache sufferers,” the review authors concluded.

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