A Framework for Estimating the Eligible Patient Population for New Migraine Acute Therapies in the United States

Clinical Guidelines19 November 2002Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine HeadacheFREEVincenza Snow, MD, Kevin Weiss, MD, Eric M. Wall, MD, MPH, and Christel Mottur-Pilson, PhD, for the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine*Vincenza Snow, MDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., Kevin Weiss, MDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., Eric M. Wall, MD, MPHFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., and Christel Mottur-Pilson, PhDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., for the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine*Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-10-200211190-00014 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Migraine headache is a common disorder seen in primary care. It affects 18% of women and 6.5% of men in the United States, almost half of whom are undiagnosed or undertreated (1, 2). These guidelines, developed by the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine, with assistance from the American Headache Society, are based on two previously published papers (3, 4). The papers, titled "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management of Acute Attacks," by Matchar and colleagues (3), and "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management for Prevention of Migraine," by Ramadan and coworkers (4), can be found at www.aan.com/professionals/practice/guidelines.cfm. 1 The target audience for this guideline is primary care physicians. The guideline applies to patients with acute migraine attacks, with or without aura, and patients with migraine who are candidates for preventive drug therapy. Although these guidelines are all based on the articles by Matchar and Ramadan and colleagues, the recommendations may differ because different thresholds of evidence were needed for making a positive recommendation. Table 1 compares the AAFP/ACP–ASIM guideline and the U.S. Headache Consortium Guideline.Table 1. Summary of U.S. Headache Consortium Recommendations Compared with AAFP/ACP–ASIM RecommendationsThroughout the text, asterisks indicate drugs that are currently not available in the United States.DiagnosisHeadache has many potential causes. Most headaches are caused by the primary headache disorders, which include migraine, cluster, and tension-type headaches. Secondary headaches, which are those with underlying pathologic causes, are far less common. Migraine is a chronic condition with recurrent acute attacks whose characteristics vary among patients and often among attacks within a single patient. Migraine is a syndrome with a wide variety of neurologic and non-neurologic manifestations. The International Headache Society (6) has developed diagnostic criteria for migraine with and without aura (Appendix Table 1). This classification system serves to diagnose headache syndromes, not patients. Thus, one patient could have more than one type of headache disorder. For example, it is not uncommon for migraine patients to also have episodic tension-type headaches.Management of Acute AttacksEffective long-term management of patients with migraine is challenging because of the complexity of the condition. Experts suggest several goals for successful treatment of acute attacks of migraine. These include treating attacks rapidly and consistently to avoid headache recurrence, to restore the patient's ability to function, and to minimize the use of backup and rescue medications.Clinicians need to educate people with migraine about their condition and its treatment and encourage them to participate in their own management. The physician must help the patient establish realistic expectations by discussing therapeutic options and their benefits and harms. Patient input can provide the best guide to treatment selection and helps the physician to better understand and accommodate patient treatment goals. Developing an effective acute migraine management strategy can be complex, and an engaged patient is more likely to negotiate this process successfully. Encouraging patients to identify and avoid triggers (Table 2) and to be actively involved in their own management by tracking their own progress may be especially useful.Table 2. Some Commonly Reported Triggers of Migraine HeadacheOnce a diagnosis of migraine is established, patients and their health care providers should decide together how to treat acute attacks and whether the patient is a candidate for preventive medications. A wide range of acute treatments with varying efficacies is currently in use (Appendix Table 2). A comprehensive review of the scientific literature, especially the data from randomized, controlled trials, provides a list of treatments that have demonstrated efficacy in the management of acute migraine headache. It also provides a clear understanding of the adverse events associated with various agents.The Headache Consortium's review of the evidence on antiemetics, barbiturate hypnotics, ergot alkaloids and derivatives, nonsteroidal anti-inflammatory drugs (NSAIDs), combination analgesics and nonopiate analgesics, opiate analgesics, triptans, and other agents found good evidence of the efficacy of only a few agents in the treatment of acute migraine (3).Available AgentsNSAIDsTheir demonstrated efficacy and favorable tolerability make NSAIDs a first-line treatment choice for all migraine attacks, including severe attacks that have responded to NSAIDs in the past. Among the NSAIDs, the most consistent evidence exists for aspirin (8-10), ibuprofen (11, 12), naproxen sodium (13, 14), tolfenamic acid* (8, 15), and the combination agent acetaminophen plus aspirin plus caffeine for the acute treatment of migraine (16). The evidence shows that acetaminophen alone is ineffective (17).Serotonin1B/1D Agonists (Triptans)There is good evidence for the effectiveness of the oral triptans naratriptan (18, 19), rizatriptan (20-23), sumatriptan (24-31), and zolmitriptan (32-34). In addition, there is good evidence for the effectiveness of subcutaneous (35-38) and intranasal (39-41) sumatriptan, making it an option for patients with nausea and vomiting. Adverse effects of the triptans include chest symptoms, but postmarketing data indicate that true ischemic events are rare. Triptans are contraindicated in patients with risk for heart disease, basilar or hemiplegic migraine, or uncontrolled hypertension. Subcutaneous sumatriptan is associated with a very rapid onset of action, and oral naratriptan is associated with a slower onset of action.ErgotaminesThere is good evidence for the efficacy and safety of intranasal dihydroergotamine (DHE) as monotherapy for acute migraine attacks (42-46). Placebo-controlled studies of intravenous DHE did not clearly establish its efficacy in the acute treatment of migraine (47, 48). The evidence was inconsistent to support efficacy of ergotamine or ergotamine–caffeine, and the studies documented frequent adverse events.OpioidsIt is well recognized that opiates are good analgesics, but there is good evidence only for the efficacy of butorphanol nasal spray (49, 50). Although opioids are commonly used, surprisingly few studies of opioid use in headache pain document whether overuse and the development of dependence are as frequent as clinically perceived. Until further data are available, these drugs may be better reserved for use when other medications cannot be used, when sedation effects are not a concern, or the risk for abuse has been addressed.Other AgentsFair evidence suggests that the antiemetic metoclopramide, given intravenously, may be an appropriate choice as monotherapy for acute attacks (51-53), particularly in patients with nausea and vomiting when the sedating side effect may also be useful. Isometheptene and isometheptene combinations obtained only borderline significance in relieving headache pain (17, 54, 55). Other agents used in practice, such as intravenous corticosteroids and intranasal lidocaine, are not effective.Choice of TreatmentSince patient responses to these therapies are not always predictable, individualized management is important. The choice of treatment should be based on, among other characteristics, the frequency and severity of attacks; the presence and degree of temporary disability; and the profile of associated symptoms, such as nausea and vomiting. The patient's history of, response to, and tolerance for specific medications must also be considered. Coexisting conditions (such as heart disease, pregnancy, and uncontrolled hypertension) may limit treatment choices.No studies document the effectiveness of specific treatment schedules, but experts suggest that acute therapy should be limited to no more than two times per week to guard against medication-overuse headache (or drug-induced headache). Medication-overuse headache is thought to result from frequent use of acute medication and has a pattern of increasing headache frequency, often resulting in daily headaches. In patients with suspected medication overuse or patients at risk for medication overuse, preventive migraine therapy should be considered.Although some use the term rebound headache interchangeably with the term medication-overuse headache, rebound headache is a distinct entity. Rebound headache is associated with withdrawal of analgesics or abortive migraine medication. There is no uniform agreement about which agents can cause rebound headache, although ergotamine (not DHE); opiates; triptans; and simple and mixed analgesics containing butalbital, caffeine, or isometheptene are generally thought to do so. There is less uniform opinion about other antimigraine agents.Another clinical consideration is the use of a self-administered rescue medication for patients with severe migraine attack that is not responding to (or failing) other treatments. A rescue medication is an agent such as an opioid or a butalbital-containing compound that the patient can use at home when other treatments have failed. Although rescue medications often do not completely eliminate pain and allow patients to return to normal activities, they permit the patient to achieve relief without the discomfort and expense of a visit to the physician's office or emergency department. A cooperative arrangement between provider and patient may extend to the use of rescue medication in appropriate situations.Summary of Treatment of Acute MigraineA body of evidence now points to effective first- and second-line agents for acute treatment of migraine. Beyond the choice of agent lies the choice of management strategy. Recently, interest and research in step care versus stratified care have increased. Step care refers to the initial use of safe, effective, and inexpensive medications as first-line agents in acute attacks of any severity. If the initial agent fails, a second-line, more expensive, migraine-specific medication is then used. The stratified care model initially stratifies migraine attacks by severity, advocating migraine-specific agents for moderate to severe attacks, regardless of previous response to or an unknown response to other agents. Which approach is more effective is still an open question (56).Management of Migraine with Preventive TherapyOnce patients and their health care providers decide how to treat acute attacks, use of preventive medications should be considered. Generally accepted indications for migraine prevention include 1) two or more attacks per month that produce disability lasting 3 or more days per month; 2) contraindication to, or failure of, acute treatments; 3) the use of abortive medication more than twice per week; and 4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction. Other factors to consider are adverse events with acute therapies, patient preference, and the cost of both acute and preventive therapies. (The U.S. Headache Consortium also produced a document on behavioral and other nonpharmacologic therapies for headache prevention, which can be found at www.aan.com/professionals/practice/guidelines.cfm.)A wide range of preventive treatments with varying efficacies is currently in use (Appendix Table 3). A comprehensive review of the scientific literature, especially the data from randomized, controlled trials, provides a list of treatments that have demonstrated efficacy in the prevention of migraine headache. It also provides a clear understanding of the adverse events associated with various agents. The Headache Consortium's review of the evidence on α2-agonists, anticonvulsants, antidepressants, β-blockers, calcium-channel blockers, NSAIDs, serotonergic agents (ergot derivatives, methysergide, and others), hormone therapy, feverfew, magnesium, and riboflavin found that there was good evidence of the efficacy of only a few agents in migraine prevention. A summary of these results follows.Available Agentsβ-BlockersEvidence consistently showed the efficacy of propranolol, 80 to 240 mg/d (57-63), and timolol, 20 to 30 mg/d (63-65), for the prevention of migraine. One trial comparing propranolol and amitriptyline suggested that propranolol is more efficacious in patients with migraine alone; amitriptyline was superior for patients with mixed migraine and tension-type headache (66). There is limited evidence of a moderate effect for atenolol (67, 68), metoprolol (69-71), and nadolol (72-74). β-Blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) seem to be ineffective for the prevention of migraine. Adverse effects reported most commonly with β-blockers were fatigue, depression, nausea, dizziness, and insomnia. These symptoms appear to be fairly well tolerated and seldom caused premature withdrawal from trials.AntidepressantsAmitriptyline has been more frequently studied than the other antidepressants and is the only one with consistent support for efficacy in migraine prevention (75-77). The dosages that were most efficacious in the clinical trials ranged from 30 to 150 mg/d. Drowsiness, weight gain, and anticholinergic symptoms were frequently reported with the tricyclic antidepressants studied, including amitriptyline. There is no evidence for the use of nortriptyline, protriptyline, doxepin, clomipramine, or imipramine. There is limited evidence of a modest effect for fluoxetine at dosages ranging from 20 mg every other day to 40 mg per day (78, 79). There is no evidence from controlled trials for the use of fluvoxamine, paroxetine, sertraline, phenelzine, bupropion, mirtazapine, trazodone, or venlafaxine.AnticonvulsantsFor the anticonvulsants, there is good evidence for the efficacy of divalproex sodium (80-82) and sodium valproate (83, 84). Adverse events with these therapies are not uncommon and include weight gain, hair loss, tremor, and teratogenic potential, such as neural tube defects. These agents may be especially useful in patients with prolonged or atypical migraine aura. Carbamazepine and vigabatrin* have been shown to be ineffective, and there is limited evidence for moderate efficacy of gabapentin (85).NSAIDsA meta-analysis (4) of five of seven placebo-controlled trials of naproxen or naproxen sodium showed a modest effect on headache prevention (62, 86-92). Similar trends were observed in single placebo-controlled trials of flurbiprofen, indobufen*, ketoprofen, lornoxicam*, and mefenamic acid and in two trials of tolfenamic acid*. Placebo-controlled trials of aspirin, aspirin plus dipyridamole, fenoprofen, and indomethacin were inconclusive. There is no evidence for the use of ibuprofen or nabumetone in the prevention of migraine.Side effect rates for naproxen were not significantly higher than those seen with placebo. The most commonly reported adverse events with all NSAIDs were gastrointestinal symptoms, including nausea, vomiting, gastritis, and blood in the stool. In the trials reviewed, such symptoms were reported by 3% to 45% of participants (86).Serotonergic AgentsOf these agents, time-released DHE* had the strongest support, with consistently positive findings in four placebo-controlled trials (93-96). Evidence is insufficient for the efficacy of ergotamine or ergotamine plus caffeine plus butalbital plus belladonna alkaloids or methylergonovine for migraine prevention. Limited information was reported on adverse events associated with these agents. The most commonly reported events for all the ergot alkaloids were gastrointestinal symptoms.There is strong evidence for the efficacy of methysergide (97-100), a semisynthetic ergot alkaloid. However, there are reports of retroperitoneal and retropleural fibrosis associated with long-term, mostly uninterrupted administration. The manufacturer suggests that methysergide therapy be discontinued for 3 to 4 weeks after each 6-month course of treatment. Other adverse events most commonly reported included gastrointestinal symptoms and leg symptoms (restlessness or pain).Other serotonergic agents that have been evaluated for the prevention of migraine include pizotifen*, lisuride*, oxitriptan*, iprazochrome*, and tropisetron*. Only lisuride (101-104) and pizotifen (87, 99, 105-110) have consistent evidence that supports their efficacy in the prevention of migraine. Published data on adverse events associated with lisuride are limited, and pizotifen is often associated with weight gain and drowsiness.Calcium-Channel BlockersThe evidence for nifedipine, nimodipine, cyclandelate*, and verapamil is poor quality and difficult to interpret, suggesting only a modest effect (see reference 4 for study references). There is no evidence for the use of diltiazem in the prevention of migraine. Symptoms reported with these agents included dizziness, edema, flushing, and constipation.Flunarizine*, 10 mg/d, has proven efficacy in the prevention of migraine and is commonly used in countries where it is available (111-115). Adverse events reported with flunarizine include sedation, weight gain, and abdominal pain. Depression and extrapyramidal symptoms can be observed, particularly in elderly persons.α2-AgonistsThere is good evidence for the lack of efficacy of the α2-agonist clonidine in the prevention of migraine (116-120). Limited evidence shows moderate efficacy of guanfacine (121).Hormone Therapy, Feverfew, Magnesium, and RiboflavinThere is fair evidence for modest efficacy of these agents in certain circumstances, but more trials need to be done. Most of the existing trials had small sample sizes, had self-referred or special patient samples, or had other methodologic flaws (see reference 4 for more details and references).Summary of Preventive TherapyTo alleviate the suffering of many patients with migraine, clinicians need to be aware of the commonly accepted indications for preventive therapy and initiate effective therapy in those patients. Although many agents are available for the preventive treatment of migraine, only a few have proven efficacy. Once an agent has been chosen, clinicians should initiate therapy with a low dose and titrate the dose slowly up until clinical benefits are achieved in the absence of adverse events or until limited by adverse events. Because a clinical benefit may take as long as 2 to 3 months to manifest, each treatment should be given an adequate trial. Once preventive treatment is under way, interfering medications, such as overused acute medications such as ergotamine, should be avoided. After a period of stability, clinicians should consider tapering or discontinuing treatment. Patient and clinician need to engage in an ongoing dialogue in which patient expectations and goals for therapy are taken into account when agents are chosen, titrated, or discontinued.RecommendationsRecommendation 1: For most migraine sufferers, nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy.To date, the most consistent evidence exists for aspirin, ibuprofen, naproxen sodium, tolfenamic acid*, and the combination agent acetaminophen plus aspirin plus caffeine. There is no evidence for the use of acetaminophen alone.Recommendation 2: In patients whose migraine attack has not responded to NSAIDs, use migraine-specific agents (triptans, DHE).There is good evidence for the following triptans: oral naratriptan, rizatriptan, and zolmitriptan; oral and subcutaneous sumatriptan; and DHE nasal spray. Few data in the literature demonstrate which triptans are more effective. Oral opiate combinations and butorphanol may be considered in acute migraine when sedation side effects are not a concern and the risk for abuse has been addressed.Recommendation 3: Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex. Treat nausea and vomiting with an antiemetic.Evidence is limited, but in some patients, concomitant treatment with an antiemetic and an oral migraine medication may be appropriate. Antiemetics should not be restricted to patients who are vomiting or likely to vomit. Nausea itself is one of the most aversive and disabling symptoms of a migraine attack and should be treated appropriately.Recommendation 4: Migraine sufferers should be evaluated for use of preventive therapy.Generally accepted indications for migraine prevention include 1) two or more attacks per month that produce disability lasting 3 or more days per month; 2) contraindication to, or failure of, acute treatments; 3) use of abortive medication more than twice per week; or 4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction.Recommendation 5: Recommended first-line agents for the prevention of migraine headache are propranolol (80 to 240 mg/d), timolol (20 to 30 mg/d), amitriptyline (30 to 150 mg/d), divalproex sodium (500 to 1500 mg/d), and sodium valproate (800 to 1500 mg/d).Medications with proven efficacy but limited published data on adverse events or frequent or severe adverse events include flunarizine*, lisuride*, pizotifen*, time-released and migraine sufferers about the of acute attacks and preventive therapy and engage them in the of a management should be on a is strong about the need for people with migraine. The physician must help the patient establish realistic expectations by discussing therapeutic options and their benefits and such as medication-overuse headache. Encouraging patients to be actively involved in their own management by tracking their own progress daily for example, may be especially useful. should attack frequency, severity, and resulting disability; response to type of and adverse effects of medication. Patient input can provide the best guide to treatment Table 1. International Headache Society Table 2. Summary of the Evidence for Acute Table Summary of the Evidence for Preventive M. and of migraine in the United data from the American Migraine Migraine diagnosis and results from the American Migraine Matchar guidelines for migraine headache in the primary care management of acute at www.aan.com/professionals/practice/guidelines.cfm. Ramadan guidelines for migraine headache in the primary care management for prevention of migraine. at www.aan.com/professionals/practice/guidelines.cfm. Matchar guidelines for migraine of and at www.aan.com/professionals/practice/guidelines.cfm. and diagnostic criteria for headache disorders, and pain. Headache of the International Headache and diagnosis of Headache in Clinical Medical acid is as effective as ergotamine migraine of an acetaminophen mg combination versus aspirin mg and in acute migraine and aspirin versus aspirin or for migraine a Treatment of acute migraine ibuprofen and A study of ibuprofen versus in the treatment of acute migraine a migraine naproxen sodium ergotamine plus caffeine. M. sodium in the treatment of migraine. metoclopramide, caffeine and their combinations in the treatment of migraine and safety of aspirin, and caffeine in migraine headache randomized, placebo-controlled Treatment of migraine with and a trial. is effective and well tolerated in the acute treatment of migraine. of a is effective and well tolerated in the acute treatment of migraine. of a The study of in migraine. sumatriptan in the acute treatment of migraine. A study of rizatriptan in the acute treatment of migraine.

A Retrospective Review of Erythrocyte Stimulating Agents (ESA) Usage in Pharmacy Claims Data.

Les antiépileptiques dans le traitement préventif de la migraine de l’enfant

To describe patient characteristics, adherence, and treatment patterns, among adult migraine patients in the United States prescribed erenumab. Migraine is a highly prevalent and debilitating disease characterized by recurrent attacks of moderate to severe headache accompanied by non-headache symptoms. Erenumab is a first-in-class calcitonin gene-related peptide receptor (CGRP-R) antagonist indicated for migraine prophylaxis in adults. This retrospective longitudinal cohort study used IQVIA's open-source longitudinal pharmacy (LRx) and medical (Dx) claims databases to identify adult migraine patients with an initial claim (index date) for erenumab between May 1, 2018 and April 30, 2019. Patients were required to have ≥180days of follow-up. Erenumab dosing patterns, persistence, and adherence (using medication possession ratio [MPR] and proportion of days covered [PDC]), and discontinuation of other commonly prescribed acute and prophylactic anti-migraine therapies were assessed. Dose changes in acute therapies after initiation of erenumab were assessed in a subset of patients with an adequate trial of erenumab (≥2 additional erenumab claims within the 80days following the index claim). A total of 64,174 patients met the study criteria. Mean (SD) age was 48 (13) years and 85.2% (n=54,656) were female. The initial erenumab dose was 70mg for the majority of patients (65.1%; n=41,790); most (81.4%; n=34,019) maintained their index dose during follow-up. Overall, 30.8% (n=19,797) of patients had a PDC≥0.80 and 41.7% (n=26,769) had a MPR≥0.80. Discontinuation rates of acute and other prophylactic migraine therapies after initiation of erenumab (among users of the respective therapies) were 48.7% (22,965/47,190) and 36.1% (16,602/46,006), respectively. Dose decreases among triptan, ergot compound, opioid, and barbiturate users were observed after initiation of erenumab. Almost all patients had prior use of acute or preventive therapy. Adherence to erenumab was higher than traditional oral prophylactic migraine therapies; however, overall adherence was still suboptimal. The decrease in use of acute and preventive prescription medications following initiation of erenumab suggests effectiveness in the real-world setting.

Several decades ago, pharmacological options for the treatment of migraine were extremely limited, reducing ability to effectively control symptoms in most patients. In recent years, significant advances have been made in understanding migraine pathophysiology and in the development of novel therapeutic approaches. Given the emergence of new drugs alongside long-standing clinical experience with established treatments, it is important to clarify the role of triptans in contemporary acute migraine management. Aim purpose of this article was to analyze the role of triptans in modern acute migraine therapy. Methods. This narrative review was conducted through systematic searches of PubMed, Scopus, and Web of Science. Articles published between 2015 and 2025 were included, with preference given to clinical guidelines, systematic reviews, meta-analyses, randomized controlled trials, and large observational studies. Literature Review and Discussion. Selecting an effective acute therapy is a critical step in migraine management for every patient. Two main strategies are recognized: the stratified approach and the escalating approach. In specialized care settings, a stratified approach — tailored to attack severity and individual patient characteristics — is generally preferred. Today, comparative efficacy among acute migraine therapies is largely based on systematic reviews and network meta-analyses. Numerous active agents demonstrate significant benefit over placebo in achieving pain relief at two hours, with triptans consistently showing the highest efficacy. Among triptans, eletriptan has demonstrated superior effectiveness. Novel agents, including lasmiditan, rimegepant, and ubrogepant, show comparatively lower efficacy but they may be valuable for patients who respond insufficiently to triptans. However, side effects and safety profile are also critical: gepants and nonsteroidal anti-inflammatory drugs exhibit advantages over triptans and ditans. Optimal use of triptans requires adherence to administration guidelines to maximize efficacy and minimize side effects. Cost-effectiveness should also be considered, as substantial price differences exist between newer agents and triptans across Europe and the United States. Conclusions. Recently, the introduction of new acute migraine therapies expands opportunities for personalized treatment. Triptans remain the most effective agents for aborting and relieving migraine attacks, whereas gepants offer alternative option for patients with inadequate response or poor tolerability to triptans. When individualizing acute therapy, the markedly lower cost of triptans compared to novel agents should be factored into clinical decision-making.

e18830 Background: A small proportion of patients (pts) with BCC develop advanced disease (locally advanced [la] and metastatic [m] BCC). Until recently, there was no standard treatment regimen for advanced BCC following progression on or intolerance to HHIs. Some pts received systemic therapy (ST), but most received best supportive care (BSC). Cemiplimab-rwlc is the first immunotherapy indicated in the US, fully for pts with laBCC and accelerated for mBCC, post HHIs or for whom HHIs are not appropriate. This study estimated the BI of introducing cemiplimab-rwlc in the US from a healthcare payer’s perspective. Methods: A decision analytic model was developed to estimate the BI of introducing cemiplimab-rwlc to a US healthcare system over 3 years for advanced BCC treatment following HHIs. Published data were used to estimate eligible patient population size. Reference case market shares for platinum chemotherapy (CT; 4%), nivolumab (3%), pembrolizumab (2%), vismodegib (1%), sonidegib (1%), and BSC (89%) were based on market research, as were predicted uptake of cemiplimab-rwlc and changes in market distribution of STs and BSC post-cemiplimab-rwlc launch, with most pts moving from BSC. Treatment costs were sourced from the ProspectoRx drug pricing database. Total costs (2020 US dollars [$]) to the healthcare system included costs related to treatment, disease monitoring, and mitigation of Grade 3–4 adverse events. Results: In a hypothetical US healthcare plan of 1,000,000 members, ̃32 pts per year with advanced BCC would be eligible for cemiplimab-rwlc, resulting in an average additional cost of cemiplimab-rwlc introduction of $0.12 per member per month (PMPM) over 3 years. The proportion of pts receiving ST rather than BSC was estimated to increase from 11% in 2020, prior to cemiplimab-rwlc approval, to 50% in 2023. Cemiplimab-rwlc market share is projected to increase by 41% by year 3 taking shares from BSC (–39%), HHIs (–1%), and CT (–1%). Given the large proportion of pts who currently receive BSC, the availability of cemiplimab-rwlc is expected to increase payers’ 3-year budget from $978,955 to $5,487,507 post-launch. A one-way sensitivity analysis showed that BI estimates were most sensitive to estimation of the size of the eligible population (health plan population [±20%], proportion of pts with advanced BCC [±20%], and those eligible for treatment post-HHI [±19%]), cemiplimab-rwlc treatment duration (±17%), and the cost of cemiplimab-rwlc (±17%). Changes to all other inputs had a < 5% impact. Conclusions: The introduction of cemiplimab-rwlc had a minimal BI on the average PMPM cost. Modest incremental BI is directly attributable to the projected uptake of cemiplimab-rwlc in a market where pts previously received no ST. These analyses provide new insights in the management of advanced BCC noting limited available evidence for post-HHI treatment.

Budget Impact of Glasdegib in Combination with Low-Dose Cytarabine for the Treatment of First-Line Acute Myeloid Leukemia in the United States

PurposeTo estimate 5-years budgetary impact of introducing mepolizumab to eligible patients with uncontrolled severe eosinophilic asthma treated at a tertiary care hospital within Dubai Health Authority (DHA).Patients and MethodsA budget impact analysis (BIA) model was adapted to the setting of Rashid Hospital, DHA to estimate the budgetary implications of introducing first-in-class anti-IL5 (mepolizumab) as add-on therapy for eligible patients with severe eosinophilic asthma. The eligible patient population (n=60) was estimated from aggregate data provided by the clinic. Patients were eligible to treatment with mepolizumab if they had ≥2 exacerbation in the previous year and eosinophil count ≥150 cell/µL. The analysis compared the cost of treating patients in two alternative scenarios; a scenario where patients are treated with optimized usual care or with available biologic as add-on therapy, and a second scenario where mepolizumab is fully accessible to eligible patients.ResultsAdministration of mepolizumab to eligible patients at Rashid Hospital is predicted to result in overall savings estimated at £270,545 over a 5-year time horizon. Exacerbation rates could not be indirectly compared for mepolizumab and omalizumab, since treatment continuation rules were defined differently. Therefore, these parameters were directly taken from the clinical trials for mepolizumab and omalizumab. The savings were estimated due to drug acquisition costs (£269,900) and estimated reduction in exacerbation (n=15). One-way sensitivity analysis showed that the model results was most sensitive to changing the method of calculating omalizumab dose and varying the drug acquisition cost of omalizumab by ±20%.ConclusionThe BIA showed that full accessibility of mepolizumab to eligible severe asthma patients is predicted to be budget saving in the Dubai Health Authority. This evaluation is relevant to healthcare decision making as it demonstrates that mepolizumab is budget saving for eligible patients, while reducing burden by improving their control and symptoms.

Objectives:A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan.Methods:The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty.Results:In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses.Conclusions:Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients’ quality-of-life were included.

CIMA

PIN77 BUDGET IMPACT ANALYSIS OF NOVEL DIRECT-ACTING ANTIVIRALS FOR TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN TAIWAN

New gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options. In May 2023, the US Food and Drug Administration (FDA) approved the first topical gene therapy, beremagene geperpavec (B-VEC), for treating both autosomal recessive and autosomal dominant dystrophic epidermolysis bullosa (DEB). However, FDA approval was based on limited data in patients with autosomal dominant disease, even though they comprise approximately 50% of all DEB cases. To estimate projected spending in the US on B-VEC therapy for treating autosomal recessive and autosomal dominant DEB. This economic evaluation used data from the National Epidermolysis Bullosa Registry to estimate the current population of US patients with autosomal dominant and autosomal recessive DEB, with the aim of estimating US spending on B-VEC therapy from an all-payers perspective during 1- and 3-year periods after FDA approval. A base-case cost of $300 000 per patient per year was assumed based on a report from the manufacturer (Krystal Biotech). Treatment with B-VEC. Estimated overall spending on B-VEC in the first year and over a 3-year period after FDA approval. Several prespecified sensitivity analyses with different assumptions about the eligible patient population and the cost of therapy were performed, and lifetime total costs of treatment per patient were estimated. The estimated number of US patients with DEB who were eligible for treatment with B-VEC in the first year after FDA approval was 894. The estimated total expenditure for B-VEC therapy was $268 million (range, $179 million-$357 million). Over a 3-year period, estimated spending was $805 million (range, $537 million-$1.1 billion). Estimated lifetime total costs per patient were $15 million (range, $10 million-$20 million) per patient with autosomal recessive DEB and $17 million (range, $11 million-$22 million) for patients with autosomal dominant DEB. Results of this economic evaluation suggest that the FDA's broad indication for the use of B-VEC in treating both autosomal recessive and autosomal dominant DEB will have significant implications for payers.

The pharmaceutical landscape has undergone a transformative shift due to emerging technologies, leading to a projected value of USD 405.52 billion for the global pharmaceutical manufacturing market in 2020. Brazil, representing 2% of the global pharmaceutical market, boasts a comprehensive public health system called Sistema Único de Saúde (SUS), ensuring universal health coverage. However, the public and private health sectors in Brazil operate independently, with 23% of Brazilians possessing private health insurance plans. Regulated by the Brazilian Drug Market Regulation Chamber (CMED), which controls drug prices based on international retail prices and other factors, the pharmaceutical market in Brazil faces significant challenges in maintaining the sustainability of the Brazilian health-care system, particularly due to the high costs of cancer medications, such as pembrolizumab and trastuzumab deruxtecan. This study aims to assess the budgetary impact of expanding indications for pembrolizumab and trastuzumab deruxtecan in Brazil after their initial registration by the Brazilian Health Regulatory Agency. Utilizing epidemiological data from the National Cancer Institute (INCA) and clinical trial data, we estimated the eligible patient populations and associated costs for these medications. Trastuzumab deruxtecan’s eligible patient population increased from 383 to 23,000 across various indications, resulting in a total cost increase from USD 90.6 million to USD 5.0 billion. Similarly, pembrolizumab’s eligible patient population expanded from 1796 to 99,544 for multiple indications, causing the total cost increase from USD 121.1 million to USD 6.7 billion. The study highlights the substantial expansions in indications and patient eligibility for trastuzumab deruxtecan and pembrolizumab in Brazil, with significant budgetary implications potentially jeopardizing the health-care system’s sustainability. To ensure the long-term sustainability of health-care systems and to provide equitable access to optimal treatments, it is crucial for policymakers to monitor and adjust drug prices following their initial registration. Policymakers must be aware of these challenges and consider them in health-care policy development and decision-making processes.

Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives. The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results. In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs. Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis. This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

BackgroundThe purpose of this study was to explore the budget impact of dutasteride plus tamsulosin fixed-dose combination (DUT + TAM FDC) versus tamsulosin monotherapy, in the treatment of patients with benign prostatic hyperplasia (BPH) from the perspective of the Greek healthcare insurance system.MethodsA Microsoft Excel-based model was developed to estimate the financial consequences of adopting DUT + TAM FDC within the Greek healthcare setting. The model, compared six mutually exclusive health states in two alternative treatment options: current standard of care and the introduction of DUT + TAM FDC in the market. The model used clinical inputs from the CombAT study; data on resource use associated with the management of BPH in Greece were derived from expert panel, and unit cost data were derived from official reimbursement tariffs. A payer perspective was taken into account. As patient distribution data between public and private sectors are not available in Greece two scenarios were investigated, considering the whole eligible population in each scenario. A 4 year time horizon was taken into account and included treatment costs, number of transurethral resections of the prostate (TURPs) and acute urinary retention (AUR) episodes avoided.ResultsThe clinical benefit from the market adoption of DUT + TAM FDC in Greece was 1,758 TURPs and 972 episodes of AUR avoided cumulatively in a four year period. The increase in total costs from the gradual introduction of DUT + TAM FDC to the Greek healthcare system ranges from €1.3 million in the first year to €5.8 million in the fourth year, for the public sector, and €1.2 million to €4.0 million, for the private sector. This represents an increase of 1.91% to 7.94% for the public sector and 1.10% 3.29% in the private sector, during the 4-year time horizon.ConclusionsBudget impact analysis (BIA) results indicated that the gradual introduction of DUT + TAM FDC, would increase the overall budget of the disease, however providing better clinical outcomes. DUT + TAM FDC drug acquisition cost is partly offset by the reduction in the costs associated with the treatment of the disease.