Medical Therapy for Chronic Migraine: Where we stand/Where we should be/ Where we are going
/
We have addressed the topic of chronic migraine (CM) in virtually every issue of this magazine since its inception. Now let’s take a few minutes both to celebrate the progress we’ve made in managing CM and to confront the very real obstacles we face in using that progress to whittle down the public health burden CM continues to impose.
Over 4% of the general population has near-daily or daily headache, and one-half of those individuals – upwards of 6 million people in the United States – have CM. Despite the high prevalence of the disorder and the emotional, physical and financial toll exacted, it is only within the past 15 years that CM was formally accepted as a primary headache disorder and has occupied a place within the International Classification of Headache Disorders. Prior to 2010 we had no – zero – evidence-based therapies for a disorder that afflicts roughly 1 in 50 Americans. Amazing, no?
Making sense of any medical disorder first requires a definition of the disorder, and to have a meaningful definition requires a uniform set of diagnostic criteria that are sensitive, specific and widely accepted.. Once such a definition is in place – and not before - prospective clinical trials can be initiated. If all goes well, those trials will yield ever-improving evidence-based management. This is what has occurred for CM. With CM receiving formal designation as a primary headache disorder and having uniform criteria to diagnose the disorder, we began to develop evidence-based therapies for the suppression of CM.
Remarkably, within those 15 years research investigators have managed to introduce into general clinical practice no less than 7 FDA-approved medications indicated for the suppression of chronic migraine. Excluding topiramate (Topamax), a notoriously difficult drug for many patients to tolerate, we have 6 FDA-approved therapies for CM that possess a strong evidence base, are known to be safe, are typically well-tolerated and are known to be effective in a high proportion of CM patients…often rapidly so. Those therapies are the 3 self-injected anti-CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality), the intravenously administered anti-CGRP monoclonal antibody (Vyepti), onabotulinumtoxinA (BotoxA) and an oral anti-CGRP “gepant”, atogepant (Qulipta).
Why then is it that only a tiny percentage of people with CM seek medical attention, are diagnosed accurately and are treated appropriately? There are multitude of reasons, but the two most important reflect (1) a lack of awareness on the part of the lay public as to what CM is and that CM is treatable, and (2) the scarcity of healthcare providers who have the knowledge, experience and inclination to diagnose and manage CM appropriately. This magazine represents a small part of the effort being made to rectify problem number 1. As for problem number 2, we have addressed the long-standing imbalance of supply (too few providers)><demand (so many headache patients in need of medical attention) in previous issues, and in this current issue is included more on the topic including one potential solution for beginning to correct that imbalance.
These are big, tough and challenging problems, and as if they are not enough to deal with there are also the obstacles placed by the healthcare insurance industry. Let’s consider several examples of those obstacles drawn from the author’s clinical practice.
AB is a 45-year-old female with a long-standing history of episodic migraine that has “transformed” to the chronic variant as she approaches menopause. She has been having headaches more days than not for over 2 years and headaches on a daily basis for the past 6 months. She has incapacitating migraine episodes about once per week and is worried that her work absences and decreased productivity on days when she attempts to work despite migraine are putting her employment at risk. She has attempted to cope with her headache disorder by taking both over-the-counter and prescription medications intended for acute headache treatment but has not yet tried any medication for headache prevention/suppression of chronic migraine. She tells her provider that she would like to try serial Botox injection therapy for that purpose, but her insurer refuses to provide authorization until she tries and fails 3 prevention medications from 3 different pharmacologic classes, all of which have potential side effects and none of which possesses any meaningful evidence base for use in treating chronic migraine.
JF is a 35-year-old female who also has a long-standing history of episodic migraine. During a pregnancy 2 years prior her previously episodic migraine “transformed” into chronic daily headache/chronic migraine, and her migraine burden remained high until she began administering subcutaneous Aimovig 70 mg monthly. Within three months she had improved from daily headache with 10 to 15 days of incapacitating migraine per month to less than five days of headache per month, all rapidly responsive to acute medication. She was quite pleased until January rolled around, when her insurer advised her that coverage for Aimovig no longer would be provided and that she would need to switch to another anti-CGRP monoclonal antibody (Ajovy or or Emgality). With the help of her provider she appealed the insurer’s denial, but the denial stood. She began administering one of the mandated monoclonal antibodies and rapidly experienced a significant increase in her migraine burden.
What precisely is going on here? How has it come to pass that healthcare providers are now compelled to abdicate patient care to administrators within the insurance industry? Why exactly is it that a medically untrained administrator who has never seen the client/patient (nor any patient) now may overrule medical management recommended by a medically trained provider who is in fact seeing the patient?
It’s all in the financial bottom line. Compared to cheap generic drugs such as amitriptyline and propranolol, to the insurer BotoxA injection therapy represents a financially exorbitant way to treat CM. Does BotoxA reduce the indirect costs associated with CM – the physical and emotional suffering, the adverse effect on quality of life, the costs associated with work absenteeism and decreased productivity? Yes. A resounding yes! Do insurers care? No. Does BotoxA reduce the direct costs associated with CM-the costs of medications used for acute headache, unneeded brain scans, trips to the ER, etc? Yes…and, in fact, to a degree that the savings in these direct costs go a very long ways towards offsetting the cost of BotoxA treatment. Do insurers care? They should, given that it is they who ultimately pay for those $5,000 ER visits and $25,000 hospitalizations. But they do not care. Too bad for patient AB. The prevention medications she has been mandated to try (and fail) may not only fail to help and possibly cause side effects, but the time required to try and fail those 3 medications may further activate the biologic circuitry that generates CM and render her headache disorder that much more difficult to treat when she finally is permitted to receive an evidence-based therapy.
Why mandate that patient JF must stop an anti-CGRP monoclonal antibody that she has responded to so well in favor of another anti-CGRP monoclonal antibody that may or may not be effective? Could it be that with the turning of the year her insurer procured a more financially advantageous contract for the alternative anti-CGRP medications? Of course! Why else would the need for change be mandated?
This capricious usurpation of physician authority is not only demoralizing, frustrating, unscientific and bordering on medical malpractice… it is also simply stupid. Short-sightedly stupid. The CM patient whose headache disorder is being ineffectively treated will be using healthcare resources as a consequence of his/her headache burden, and, again, it doesn’t take many trips to the ER for a severe migraine headache to exceed the modest savings that result from forcing the patient to forego an evidence-based and appropriate therapy in favor of one that is generic and cheap.
This is a major problem, and healthcare providers are caught squarely in the middle. As a clinical neuroscientist who has assisted in the development of many new therapies for stroke and for migraine, I know how satisfying it can be to shepherd a new therapy through the research process, witness its emergence into clinical practice, prescribe it for patients in need and share with the patient the joy of a strikingly positive clinical response. The reverse is also true. It is extraordinarily dispiriting to go through that same process with a new therapy but to witness the patient being barred from the therapy by the insurer… followed by many entirely uncompensated hours spent trying to convince a succession of administrators to allow the patient to receive the therapy you consider to be in the patient’s best interest. It is beyond frustrating. It is disgusting.
Fortunately, there now are appearing in the medical literature articles clearly indicating the superiority of the new evidence-based CM therapies over the generic/cheap older therapies beloved by the insurance industry. Paralleling this is ever-more evidence indicating that the higher cost of the newer therapies may be offset by a reduction in healthcare resource utilization by those fortunate enough to receive the therapies. Improved access to the newer therapies is likely to result.
So that’s where we are with CM at present, but where are we going? It will not be enough to win the battle to have the present therapies made available to all who need them. As good as these new therapies are, there remains a significant percentage of the CM population who simply are not going to respond to what we have developed to date. Their “migraine biology” presumably is different, and for them CGRP simply may not be as important a factor in their migraine circuitry as it is in individuals who respond to the anti-CGRP therapies. Rather than churning out yet more anti-CGRP drugs, those investigators who work in migraine therapeutics now are turning their attention to other targets in the migraine circuitry, and if the experience of the past 15 years holds, look for the 6 CM suppression therapies listed earlier to be joined by other evidence-based therapies destined to “work” even when the existing 6 do not.
So, not all CM patients are treatment responders, and the insurers are decidedly a problem, but to borrow from Winston Churchill, in the past 15 years the diagnosis and treatment of CM has moved from the dark valley of the unknown to the sunlit uplands.
