MARKET INSIGHTS Summit on the Future Treatments in Migraine and Cluster Headaches Findings from the AMCP Market Insights Program by attacks of throbbing, often unilateral pain that are Meeting Objective exacerbated by physical activity and associated with photophobia, phonophobia, nausea, vomiting, and, in • Understand how AMCP members identify and many patients, cutaneous allodynia.1 Severe headache manage members with migraine and cluster and migraine are common in the U.S., with 20% of women headaches and approximately 10% of men aged ≥ 18 years reporting • Identify how payers establish coverage criteria for they had at least one in the past 3 months.2 The burden of new migraine therapies illness is often substantial, attacks can significantly impair • Define key information required for payers to aid functional ability at work, school, home, and in social product differentiation, treatment protocols, and situations.3,4 utilization review to ensure optimal outcomes for Migraines are often described as recurrent throbbing members or pulsating, moderate to severe, and often unilateral pain • Define the role of non-pharmaceutical treatment that lasts 4-72 hours with complete freedom between options in patient management the attacks (episodic). The headache is associated with nausea, vomiting and/or sensitivity to light, sound or smell. Cluster headache affects only 0.1% of the population; but patients suffer severe unilateral pain mainly in the first Introduction division of the trigeminal nerve, with associated prominent Headache is one of the most common symptoms in the unilateral cranial autonomic symptoms and a sense of general population, but despite its high prevalence and agitation and restlessness during the attacks. impairment, migraine is of ten not recognized or effectively Cluster headache is less common, but the most treated. Researchers have been working for decades to prevalent in the category of headache disorder termed develop a “targeted” therapies specifically for headaches. trigeminal autonomic cephalalgia. Cluster headaches Fortunately, with aid from advanced technology and are characterized by the short duration, they are strictly clinical innovations, there are new treatment options unilateral and have accompanying autonomic features of available for patients - including CGRP inhibitors and to lacrimation, rhinorrhea, conjunctival injection and ptosis.6 other therapies headed for Food and Drug Administration The changing seasons are the most common trigger for (FDA) approval, and a growing class of non-pharmaceutical cluster headaches, which often occur in the spring or devices that work via nerve stimulation. As new classes of drugs and non-drug treatments come to market health care providers and payers will need up-to-date Figure 1. Market Insights Forum Participant Mix evidence and guidance for the use and coverage of novel treatments. To understand the appropriate and cost effective use of novel treatments, AMCP convened an expert 15% forum of stakeholders. Forum participants included representatives from regional and national health 31% plans, integrated delivery networks, 340b entities and pharmacy benefit managers. (Figure 1). Participants discussed the differentiation of migraine and cluster headaches, treatment and prevention therapies, pipeline 39% 15% pharmaceuticals and devices, and the impact of new treatments on formulary management and the delivery of care. Differentiation of Headaches Pharmacy Benefit Manager The most common primary headache disorders are IDN/health system or 340B hospital entity Regional payer tension-type headache, migraine, and cluster headache. Nationa health plan Migraine is a chronic neurologic disease characterized April 2020 Market Insights 1 MARKET INSIGHTS Summit on the Future Treatments in Migraine and Cluster Headaches Table 1. ICHD-3 Criteria for Episodic and Chronic Migraine5 Episodic migraine Chronic migraine A. At least 5 attacks fulfilling criteria B–D A. Migraine-like or tension-type-like headache on ≥ 15 days/ B. Headache attacks lasting 4-72 hours (when untreated or month for > 3 months that fulfill criteria B and C unsuccessfully treated) B. Occurring in a patient who has had at least 5 attacks fulfilling C. Headache has at least 2 of the following 4 characteristics: criteria B-D for migraine without aura and/or criteria B and C for migraine with aura 1. Unilateral location C. On ≥ 8 days/month for > 3 months, fulfilling any of the 2. Pulsating quality following: 3.Moderate or severe pain intensity 1. Criteria C and D migraine without aura 4.Aggravation by or causing avoidance of routine physical 2. Criteria B and C for migraine with aura activity (e.g., walking or climbing stairs) 3. Believed by the patient to be migraine at onset and relieved D. During headache at least 1 of the following: by a triptan or ergot derivative 1. Nausea and/or vomiting D. Not better accounted for by another diagnosis 2. Photophobia and phonophobia E. Not better accounted for by another diagnosis ICHD = International Classification of Headache Disorders. While cluster headaches and migraines are clinically “I don’t think the plan makes a good differentiated some managed care organizations are job of differentiating migraines challenged to separate out the headache diagnosis in their pharmacy claims data. Participants noted that the from cluster headaches. I think they specific type of headache may not always be able to be [cluster headaches and migraine] just determined with claims data, and raised the possible limitation of using claims data as there is thought to be get lumped in the same category. I general unawareness of the different diagnostic codes for would have no way, if I asked my data various types of headaches within pharmacy. Diagnostic delays can limit the ability to administer analyst to pull that out…” appropriate acute and preventative treatments. An analysis from the American Migraine Prevalence and Prevention autumn. Due to their seasonal nature, cluster headaches (AMPP) Study showed that the majority of individuals with are often mistakenly associated with allergies or sinusitis. migraine had not received a correct diagnosis (79.8%) nor Early acute treatment for both types of headaches specific acute (68.4%) or preventive (60.0%) medications.7 is important, and for patients not responding to over- However, patients consulting a specialist were nearly 1.5 the-counter nonspecific pain medications, the use of times more likely to receive a chronic migraine diagnosis specific migraine medications is recommended. The most than those consulting other HCPs. commonly used migraine specific medication class for acute treatment are “triptans” (5-hydroxytryptamine [5- “I think this access [to the HT] 1b/1d receptor agonists). Recent developments and the emergence of novel medications, device technologies, appropriate provider] is probably the and biologics have advanced treatment options for single biggest issue that we’re facing patients with migraine and cluster headaches. Diagnoses of migraine can be classified based on the in looking in some of these therapies frequency of monthly migraine days (MMDs) and monthly and some of these disease states.” headache days (MHDs); patients with fewer than 15 MMDs or MHDs have episodic migraine, and those with at The ability to access qualified physician specialists was least 15 MHDs, of which at least 8 are MMDs, have chronic discussed as a challenge due to the limited number of migraine (Table 1).2 About 2 to 3 percent of patients available headache specialists (approximately 500 UCNS with episodic migraine will transform to having chronic certified headache medicine specialists in the U.S.),8 migraine in a given year. neurologists, and geographical locations, e.g. rural vs. 2 Market Insights April 2020 MARKET INSIGHTS Summit on the Future Treatments in Migraine and Cluster Headaches Table 2. Pharmacotherapy with Evidence of Efficacy in Migraine Treatment8 Level A Level B Triptans Anti-emetics: DHE Nasal Spray IV Metoclopramide & Prochlorperazine NSAIDs: Anti-dopamine: Diclofenac, aspirin, naproxen, ibuprofen IV Chlorpromazine & Droperidol IV Acetaminophen Ergots: Acetaminophen/aspirin/caffeine 500/500/130 mg IM/IV DHE Acetaminophen 1000 mg (for non-incapacitating attacks) NSAIDS: Butorphanol nasal spray Ketorolac Opioids: Codeine/acetaminophen, Tramadol/acetaminophen Level A = Established as effective for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)* Level B = Probably effective for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.) urban settings. As a result, patients often seek migraine care from their primary care physician (PCP). While initial Emerging Agents evaluation of headache care is appropriate by a non- Emerging agents with novel mechanisms of action that specialist clinician (e.g. PCP), several payers preferred have demonstrated efficacy for the acute treatment patients with severe headaches or those resistant to of migraine include the small molecule calcitonin gene-related peptide (CGRP) receptor antagonists, treatment see a specialist who could appropriately ubrogepant and rimegepant, and lasmiditan a evaluate the headache disorder and select subsequent selective serotonin (5 -HT1F) receptor agonist (Table 3). treatments. Unlike triptans and ergotamine derivatives, these To ensure optimal outcomes for their members, payers novel