John Rothrock, MD

In assessing chronic medical disorders that adversely affect quality of life, including disorders such as malaria, acquired immunodeficiency syndrome, and sickle cell anemia, the World Health Organization has ranked migraine as the number 1 disorder for women. The diagnosis of chronic migraine (CM) implies an established history of migraine, including 15 or more days of headache per month. This clinical variant accounts for a disproportionate share of the public health burden generally imposed by migraine. One of the great paradoxes of migraine is that, despite this outsized burden, as few as 5% of the millions of Americans with CM seek medical attention, are diagnosed accurately, and receive appropriate therapy.

Why is this? The answer lies in part with the relatively recent formal recognition of CM as a distinct primary headache disorder. Not until the 2006 revision of the International Classification of Headache Disorders were widely accepted diagnostic criteria for CM available. Without such criteria in place, meaningful clinical research (and therapeutic research in particular) is impossible. As recently as 2009, we consequently lacked any evidence-based therapies for suppression of CM. In what may be a therapeutic revolution unrivaled in almost any other area of clinical medicine, within 15 years we have identified and introduced into general clinical practice no fewer than 6 new evidence-based therapies for suppression of CM that are safe, generally well tolerated, and effective. Those therapies are onabotulinumtoxin A, an orally administered atogepant, the 3 subcutaneously self-administered anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (erenumab, galcanezumab, and fremanezumab), and the intravenously administered anti-CGRP monoclonal antibody eptinenzumab. A seventh and older therapy, topiramate, could be included in that group, except tolerability issues reduce its utility.

As we presently lack adequate active vs active comparator trials, at this point there is no “best” among these 6 CM therapies. Each is effective in reducing migraine burden substantially in a large proportion of patients. In many cases, the onset of the positive treatment response is gratifyingly rapid. Are they disease-modifying therapies (DMTs) that, in addition to suppressing symptoms, can alter the disorder’s biologic underpinnings and its long-term course? Put another way, does their benefit extend beyond the period of time the patient is actively on treatment? Given their relative newness, the answer is unknown. However, preliminary evidence suggests that onabotulinumtoxin A may qualify as a DMT. The US Food and Drug Administration indicated onabotulinumtoxin A for CM in 2010, and it is the first of the group introduced into clinical practice.

Complicating clinical use of these 6 therapies for suppression of CM have been various proscriptions emanating from the health care insurance industry. Chief among these has been the oft-encountered mandate that, for 1 of these 6 evidence-based treatments to be authorized for coverage, the patient with CM first must fail an “adequate” trial of multiple older, generic, and less costly therapies commonly used for prophylaxis in episodic migraine. But, with the exception of frequently difficult-to-tolerate topiramate, these therapies have no meaningful evidence base for use in CM. Furthermore, some limited evidence suggests that the efficacy of the evidence-based treatments may be less robust in patients whose CM has been longstanding. Therefore, spending many months prescribing a succession of therapies lacking an evidence base seems counterproductive and contrary to the patient’s best interests, when evidence-based therapies are available. In addition, the higher cost of evidence-based therapies may be offset by their reduction in the direct medical costs that result from clinical improvement.

The American Headache Society (AHS) recently published a position statement recommending that the CGRP-targeting medications─both the small molecule gepants and the large molecule monoclonal antibodies─be considered first-line treatment for migraine prevention. An estimated 40% of patients with migraine require prevention therapy. The soundness of the AHS recommendation is especially evident in the sizeable subset of that population with CM; for treatment of CM, this list of recommended first-line therapies logically can be extended to include onabotulinumtoxin A. In their consensus statement the AHS acknowledged the relatively higher cost of these therapies but noted the resulting reduction in direct and indirect costs could justify their use.

Migraine ranks near or at the top of the list of chronic medical disorders that adversely impact public health. CM, a common variant of migraine, is particularly adept at eroding quality of life. Presently available are 6 safe and typically well-tolerated therapies, known to be effective for treating CM and potentially capable of modifying its long-term course. Although the cost of these exceeds the cost of older generic therapies commonly used for migraine prophylaxis, those older therapies generally lack any meaningful evidence base for use in CM. In addition, prescription of these older therapies may delay easing the CM patient’s migraine burden without any associated reduction in long-term net cost. Both medically and financially, a strong case can be made for designating these 6 medications as first-line therapy for CM. Insurers, the ball is now in your court.

In assessing chronic medical disorders that adversely affect quality of life, including disorders such as malaria, acquired immunodeficiency syndrome, and sickle cell anemia, the World Health Organization has ranked migraine as the number 1 disorder for women. The diagnosis of chronic migraine (CM) implies an established history of migraine, including 15 or more days of headache per month. This clinical variant accounts for a disproportionate share of the public health burden generally imposed by migraine. One of the great paradoxes of migraine is that, despite this outsized burden, as few as 5% of the millions of Americans with CM seek medical attention, are diagnosed accurately, and receive appropriate therapy.

Why is this? The answer lies in part with the relatively recent formal recognition of CM as a distinct primary headache disorder. Not until the 2006 revision of the International Classification of Headache Disorders were widely accepted diagnostic criteria for CM available. Without such criteria in place, meaningful clinical research (and therapeutic research in particular) is impossible. As recently as 2009, we consequently lacked any evidence-based therapies for suppression of CM. In what may be a therapeutic revolution unrivaled in almost any other area of clinical medicine, within 15 years we have identified and introduced into general clinical practice no fewer than 6 new evidence-based therapies for suppression of CM that are safe, generally well tolerated, and effective. Those therapies are onabotulinumtoxin A, an orally administered atogepant, the 3 subcutaneously self-administered anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (erenumab, galcanezumab, and fremanezumab), and the intravenously administered anti-CGRP monoclonal antibody eptinenzumab. A seventh and older therapy, topiramate, could be included in that group, except tolerability issues reduce its utility.

As we presently lack adequate active vs active comparator trials, at this point there is no “best” among these 6 CM therapies. Each is effective in reducing migraine burden substantially in a large proportion of patients. In many cases, the onset of the positive treatment response is gratifyingly rapid. Are they disease-modifying therapies (DMTs) that, in addition to suppressing symptoms, can alter the disorder’s biologic underpinnings and its long-term course? Put another way, does their benefit extend beyond the period of time the patient is actively on treatment? Given their relative newness, the answer is unknown. However, preliminary evidence suggests that onabotulinumtoxin A may qualify as a DMT. The US Food and Drug Administration indicated onabotulinumtoxin A for CM in 2010, and it is the first of the group introduced into clinical practice.

Complicating clinical use of these 6 therapies for suppression of CM have been various proscriptions emanating from the health care insurance industry. Chief among these has been the oft-encountered mandate that, for 1 of these 6 evidence-based treatments to be authorized for coverage, the patient with CM first must fail an “adequate” trial of multiple older, generic, and less costly therapies commonly used for prophylaxis in episodic migraine. But, with the exception of frequently difficult-to-tolerate topiramate, these therapies have no meaningful evidence base for use in CM. Furthermore, some limited evidence suggests that the efficacy of the evidence-based treatments may be less robust in patients whose CM has been longstanding. Therefore, spending many months prescribing a succession of therapies lacking an evidence base seems counterproductive and contrary to the patient’s best interests, when evidence-based therapies are available. In addition, the higher cost of evidence-based therapies may be offset by their reduction in the direct medical costs that result from clinical improvement.

The American Headache Society (AHS) recently published a position statement recommending that the CGRP-targeting medications─both the small molecule gepants and the large molecule monoclonal antibodies─be considered first-line treatment for migraine prevention. An estimated 40% of patients with migraine require prevention therapy. The soundness of the AHS recommendation is especially evident in the sizeable subset of that population with CM; for treatment of CM, this list of recommended first-line therapies logically can be extended to include onabotulinumtoxin A. In their consensus statement the AHS acknowledged the relatively higher cost of these therapies but noted the resulting reduction in direct and indirect costs could justify their use.

Migraine ranks near or at the top of the list of chronic medical disorders that adversely impact public health. CM, a common variant of migraine, is particularly adept at eroding quality of life. Presently available are 6 safe and typically well-tolerated therapies, known to be effective for treating CM and potentially capable of modifying its long-term course. Although the cost of these exceeds the cost of older generic therapies commonly used for migraine prophylaxis, those older therapies generally lack any meaningful evidence base for use in CM. In addition, prescription of these older therapies may delay easing the CM patient’s migraine burden without any associated reduction in long-term net cost. Both medically and financially, a strong case can be made for designating these 6 medications as first-line therapy for CM. Insurers, the ball is now in your court.

In assessing chronic medical disorders that adversely affect quality of life, including disorders such as malaria, acquired immunodeficiency syndrome, and sickle cell anemia, the World Health Organization has ranked migraine as the number 1 disorder for women. The diagnosis of chronic migraine (CM) implies an established history of migraine, including 15 or more days of headache per month. This clinical variant accounts for a disproportionate share of the public health burden generally imposed by migraine. One of the great paradoxes of migraine is that, despite this outsized burden, as few as 5% of the millions of Americans with CM seek medical attention, are diagnosed accurately, and receive appropriate therapy.

Why is this? The answer lies in part with the relatively recent formal recognition of CM as a distinct primary headache disorder. Not until the 2006 revision of the International Classification of Headache Disorders were widely accepted diagnostic criteria for CM available. Without such criteria in place, meaningful clinical research (and therapeutic research in particular) is impossible. As recently as 2009, we consequently lacked any evidence-based therapies for suppression of CM. In what may be a therapeutic revolution unrivaled in almost any other area of clinical medicine, within 15 years we have identified and introduced into general clinical practice no fewer than 6 new evidence-based therapies for suppression of CM that are safe, generally well tolerated, and effective. Those therapies are onabotulinumtoxin A, an orally administered atogepant, the 3 subcutaneously self-administered anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (erenumab, galcanezumab, and fremanezumab), and the intravenously administered anti-CGRP monoclonal antibody eptinenzumab. A seventh and older therapy, topiramate, could be included in that group, except tolerability issues reduce its utility.

As we presently lack adequate active vs active comparator trials, at this point there is no “best” among these 6 CM therapies. Each is effective in reducing migraine burden substantially in a large proportion of patients. In many cases, the onset of the positive treatment response is gratifyingly rapid. Are they disease-modifying therapies (DMTs) that, in addition to suppressing symptoms, can alter the disorder’s biologic underpinnings and its long-term course? Put another way, does their benefit extend beyond the period of time the patient is actively on treatment? Given their relative newness, the answer is unknown. However, preliminary evidence suggests that onabotulinumtoxin A may qualify as a DMT. The US Food and Drug Administration indicated onabotulinumtoxin A for CM in 2010, and it is the first of the group introduced into clinical practice.

Complicating clinical use of these 6 therapies for suppression of CM have been various proscriptions emanating from the health care insurance industry. Chief among these has been the oft-encountered mandate that, for 1 of these 6 evidence-based treatments to be authorized for coverage, the patient with CM first must fail an “adequate” trial of multiple older, generic, and less costly therapies commonly used for prophylaxis in episodic migraine. But, with the exception of frequently difficult-to-tolerate topiramate, these therapies have no meaningful evidence base for use in CM. Furthermore, some limited evidence suggests that the efficacy of the evidence-based treatments may be less robust in patients whose CM has been longstanding. Therefore, spending many months prescribing a succession of therapies lacking an evidence base seems counterproductive and contrary to the patient’s best interests, when evidence-based therapies are available. In addition, the higher cost of evidence-based therapies may be offset by their reduction in the direct medical costs that result from clinical improvement.

The American Headache Society (AHS) recently published a position statement recommending that the CGRP-targeting medications─both the small molecule gepants and the large molecule monoclonal antibodies─be considered first-line treatment for migraine prevention. An estimated 40% of patients with migraine require prevention therapy. The soundness of the AHS recommendation is especially evident in the sizeable subset of that population with CM; for treatment of CM, this list of recommended first-line therapies logically can be extended to include onabotulinumtoxin A. In their consensus statement the AHS acknowledged the relatively higher cost of these therapies but noted the resulting reduction in direct and indirect costs could justify their use.

Migraine ranks near or at the top of the list of chronic medical disorders that adversely impact public health. CM, a common variant of migraine, is particularly adept at eroding quality of life. Presently available are 6 safe and typically well-tolerated therapies, known to be effective for treating CM and potentially capable of modifying its long-term course. Although the cost of these exceeds the cost of older generic therapies commonly used for migraine prophylaxis, those older therapies generally lack any meaningful evidence base for use in CM. In addition, prescription of these older therapies may delay easing the CM patient’s migraine burden without any associated reduction in long-term net cost. Both medically and financially, a strong case can be made for designating these 6 medications as first-line therapy for CM. Insurers, the ball is now in your court.