Monthly migraine days, tablet utilization, and quality of life associated with Rimegepant - post hoc results from an open label safety study (BHV3000-201).

BACKGROUND: The objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks. METHODS: Eligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-specific quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free. RESULTS: One thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of 0.08 incremental QALYs were associated with rimegepant use. CONCLUSION: For subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03266588 .

A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine.

OBJECTIVE: This multi-center pilot study compared the efficacy of onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and widely accepted treatment for prevention of migraine) in individuals with chronic migraine (CM). METHODS: A total of 59 subjects with CM were randomly assigned to one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections, Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets. Subjects maintained daily headache diaries over a 4-week baseline period and a 12-week active study period. The primary endpoint was the Physician Global Assessment, which measured the treatment responder rate and indicated improvement in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12, included headache days per month, migraine days, headache-free days, days on acute medication, severity of headache episodes, Migraine Impact & Disability Assessment, Headache Impact Test, effectiveness of and satisfaction with current treatment on the amount of medication needed, and the frequency and severity of migraine symptoms. At 12 weeks subjects were re-evaluated and tapered off oral study medications over a 2-week time period. Subjects not reporting a >50% reduction of headache frequency at 12 weeks were invited to participate in a 12-week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered for this extension from weeks 14 to 26. RESULTS: This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall, the results were statistically significant within groups but not between groups. By week 26, subjects had a reduction of headache days per month compared with baseline. This was a significant within-group finding. CONCLUSION: OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.

Sinus problems as a cause of headache refractoriness and migraine chronification.

Sinus headache is not a diagnostic term supported by the academia, yet it appears to be understood by the general public and larger medical community. It can be considered both a primary and secondary headache disorder. As a primary headache disorder, most of the patients considered to have sinus headache indeed have migraine (migraine with sinus symptoms). Yet it is also possible that some attacks of sinus headache may represent a unique clinical phenotype of migraine or be a unique clinical entity. Potentially, primary sinus headache can chronify and be refractory through immune-mediated mechanisms or as a catalyst for migraine chronification through ineffective treatment or medication overuse and misuse. As a secondary headache disorder, sinus headache can be associated with a wide range of underlying etiologies such as infection, anatomical abnormalities, trauma, and immunological disease or sleep disorders. It is possible that these underlying pathophysiological processes generate long-standing activation of nociceptive mechanisms involved in headache and can lead to chronification and refractoriness of the headache symptomatology. This article explores some of the potential mechanisms and the available scientific studies that may explain how sinus headache can become chronic and present to the clinician as a refractory headache disorder.

Botulinum toxin type A as migraine preventive treatment in patients previously failing oral prophylactic treatment due to compliance issues.

OBJECTIVE: To examine the efficacy and safety of and satisfaction with botulinum toxin type A (BoNTA; BOTOX: Allergan, Inc., Irvine, CA) for prophylactic treatment of migraine headache in patients previously failing prophylaxis because of issues pertaining to compliance. Background.- Numerous factors (eg, adverse effects, tolerability, cost, frequency of dosage, hesitancy to take daily medication, failure to complete treatment) negatively influence compliance with the preventive pharmacology for migraine prophylaxis. BoNTA may offer benefit in improving compliance because of its long duration of action, injectable route of administration, and its tolerability (adverse event [AE]) profile. METHODS: This was a randomized, double-blind, single-center, placebo-controlled study (months 1 to 3) of BoNTA with a cross-over to open-label BoNTA treatment (months 4 to 6). Criteria for enrollment included patients with disabling headache (International Headache Society, International Classification of Headache Disorders [ICHD-I] diagnosis 1.1, 1.2, 1.7, or 2.2, and Headache Impact Test [HIT]-6 scores >/=56) previously failing prophylaxis because of compliance, tolerability, or adherence issues. After baseline evaluation, subjects were randomized 2 : 1 to a single set of BoNTA (139 units [U] total; 17 sites/6 muscle groups) or placebo injections. After month 3, only placebo-treated subjects were eligible to receive BoNTA in the open-label continuation study. Treatment outcomes were evaluated by headache episodes and days and maximum headache severity. Headache impact was assessed by the HIT-6, Migraine Disability Assessment (MIDAS) score, and Quality of Life (QoL) questionnaires. Treatment satisfaction was assessed with the Migraine Impact Questionnaire (MIQ), which included MIDAS and QoL. RESULTS: Of the 73 subjects screened, 61 (40 BoNTA; 21 placebo) with migraine headache diagnosis 1.1 and 1.2 who met all study criteria were enrolled in the 3-month, blinded study, with 54 completing the study; 19 of 21 placebo-treated subjects participated in the open-label period (months 4 to 6), with 18 completing the study. Between-group comparisons, demonstrated through analysis of the subjects' headache diaries, did not reach statistical significance at months 1 to 3 for the number of headache episodes or days (primary endpoint). At month 2, a decrease from baseline in the number of headache episodes (-0.99 +/- 2.38; P = .0147 vs 0.42 +/- 3.23; P = not significant [NS]) and headache days (-1.52 +/- 3.84; P = .0194 vs 0.23 +/- 4.67; P = NS) was noted in the BoNTA-treated subjects but not in the placebo-treated subjects, respectively. During the open-label study, BoNTA-treated subjects had a decrease in the number of headache episodes at months 5 and 6 (-1.58 +/- 2.88 and -1.58 +/- 2.85, respectively; P < .05 vs baseline for both) and headache days at months 5 and 6 (-2.84 +/- 4.47 and -2.73 +/- 4.86, respectively; P < .05 vs baseline for both). BoNTA did not affect maximum headache severity compared with baseline or placebo during the first 3 months of the study. A decrease in HIT-6 scores was significantly greater for BoNTA-treated subjects than for placebo-treated subjects at month 3 (-7.77 vs -3.58, P = .0466). Within-group decreases in HIT-6 scores were significant in BoNTA-treated subjects during each month of the blinded trial (-5.10 +/- 8.85, -6.63 +/- 7.49, -7.77 +/- 8.78 for months 1 to 3, respectively; P < .0001 for all vs baseline) and throughout the open-label portion of the study (-7.89 +/- 6.48, -10.39 +/- 10.81, -9.00 +/- 11.12 for months 4 to 6, respectively; P < .01 for all vs baseline). The within-group decrease in placebo-treated subjects was significant at months 1 and 3 (-3.35 +/- 6.07 and -3.58 +/- 5.40, respectively; P < .05 for both). At 3 months, BoNTA was significantly better than placebo (P = .001) in the reduction of MIDAS total score. The change from baseline in the MIDAS total scores was significant in BoNTA-treated subjects (-21.62 +/- 38.70; P < .0001) but not in placebo recipients (4.76 +/- 18.85; P = NS). BoNTA-treated subjects showed improvement in 11 of 13 and 7 of 13 assessments of treatment satisfaction in MIQ at months 3 and 6, respectively, while the placebo group showed no improvement at any measured time interval in the study. At month 3 (blinded period), there were no treatment-related AEs reported in both groups. However, there were 18 possible/probable occurrences of treatment-related AEs in the BoNTA group. At month 6 (open-label period), 4 treatment-related AEs were reported, along with 2 possible occurrences. The majority of treatment-related AEs were transient and mild to moderate in severity, with no subjects discontinuing the study because of AEs. CONCLUSIONS: BoNTA-treated subjects showed improvements from baseline in measures of headache frequency, and improvements from baseline and in comparison with placebo treatment in headache impact and treatment satisfaction at multiple time points in this study. However, BoNTA-treated subjects did not differ from placebo-treated subjects in measures of headache frequency and severity. BoNTA may be a useful treatment option for headache patients demonstrating poor compliance, adherence, or AE profile with oral prophylactic regimens.

Diagnosis of menstrual headache and an open-label study among those with previously undiagnosed menstrually related migraine to evaluate the efficacy of sumatriptan 100 mg.

BACKGROUND: Headache associated with menses is often not formally diagnosed. OBJECTIVES: The goal of this study was to evaluate patients with menstrual headache who had never previously been diagnosed with migraine and assign 1988 International Headache Society (IHS) diagnoses to their menstrual headaches. Secondary objectives included evaluation of the treatment efficacy of newly diagnosed menstrually related migraine (MRM) with sumatriptan 100 mg and patient satisfaction with sumatriptan versus satisfaction with previous therapy. METHODS: Patients were recruited via advertisement in a local daily newspaper, and headache diagnosis and eligibility criteria of respondents were assessed by telephone. During telephone screening, IHS criteria for headache were applied to symptoms described by patients as menstrual headache. Those with previously undiagnosed headaches who fulfilled criteria for migraine without or with aura (IHS 1.1 or 1.2) and all inclusion/exclusion criteria at visit 1 were provided with sumatriptan 100 mg to treat 1 MRM. Patients were instructed to treat their next MRM as early as possible after the onset of headache. A treatment diary was provided with study medication for documentation of headache pain severity and associated symptoms; time of treatment and response at 30, 60, and 90 minutes and at 2, 4, 24, and 48 hours posttreatment; medication for persistence or recurrence; adverse effects; and onset of menstrual cycle. In analysis, headache response was defined as a reduction in pretreatment head pain from moderate or severe to mild or no pain. RESULTS: A total of 153 patients responded to an advertisement seeking menstrual headache sufferers. After the preliminary screening by telephone, 105 patients were assigned IHS diagnoses based on reported symptoms associated with their menstrual headache. Overall, 63% (66/105) fulfilled criteria for IHS 1.1 (migraine without aura), 12% (13/105) met criteria for IHS 1.2 (migraine with aura), and 5% (5/105) met criteria for IHS 1.7 (migrainous disorder). Of the 79 patients meeting the criteria for IHS 1.1 or 1.2, 45 patients were enrolled. Thirty-nine (mean age, 34.8 years; mean duration of experiencing menstrual headaches, 11.1 years) of the 45 patients treated 1 MRM with sumatriptan 100 mg per protocol (6 patients were lost to follow-up or withdrew consent). Headache response was reported by 70% of patients at 2 hours and 86% at 4 hours. The pain-flee response after treatment at the moderate or severe phase occurred in 41% of patients at 2 hours and in 61% at 4 hours. All 39 patients reported previous use of nonsteroidal anti-inflammatory medications for acute treatment of headache; in addition, 1 of the 39 also took acetylsalicylic acid/caffeine/butalbital, 1 took acetaminophen/caffeine/butalbital, 1 took ketorolac, and 1 took acetaminophen plus codeine. In terms of patient satisfaction, 69% of patients were satisfied with sumatriptan versus 15% of patients who were satisfied with their previous therapy. CONCLUSIONS: Seventy-five percent of women with previously undiagnosed menstrual headaches met diagnostic criteria for migraine in this small sample. Two hours after treatment with sumatriptan 100 rag, 70% of patients with headaches treated at moderate to severe pain had a pain relief response (reduction to mild or no pain).

Sumatriptan: update and review.

Sumatriptan is the first of a novel class of medications referred to as triptans. Since its approval for migraine in the 1990s, six other triptan products have received FDA approval. Despite the proliferation of triptans, sumatriptan remains the most frequently prescribed product in this therapeutic class. Sumatriptan has been instrumental in defining a biological basis for migraine. It is effective in treating migraine with or without aura, well tolerated and, when properly prescribed, safe. Sumatriptan injection is the only member of the triptan class approved for treatment of cluster headache. Studies with sumatriptan have also advanced the therapeutic intervention paradigm that permits patients to treat earlier and avoid substantial disability. Numerous pharmacoeconomic studies have demonstrated that sumatriptan decreases work loss productivity and improves quality of life.

An otolaryngology, neurology, allergy, and primary care consensus on diagnosis and treatment of sinus headache.

While "sinus" headache is a widely accepted clinical diagnosis, many medical specialists consider it to be an uncommon cause of recurrent headaches. Unnecessary diagnostic studies, surgical interventions, and medical treatments are often the result of the inappropriate diagnosis of sinus headache. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to characterize conditions leading to headaches of rhinogenic origin. However, they have done so from different perspectives and in isolation from the other specialty groups. An interdisciplinary ad hoc committee recently convened to discuss the role of sinus disease and the nose in the etiology of headache and to review recent epidemiologic studies suggesting that sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. Clinical trial data are presented which clearly indicate that the majority of sinus headaches can actually be classified as migraines. This committee reviewed scientific evidence available from multiple disciplines and concludes that considerable research and clinical study are needed to further understand and explain the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, there was a consensus from this group that greater diagnostic and therapeutic attention needs to be given to patients complaining of sinus headache that may indeed be due to the nose.

Sinus headache, migraine, and the otolaryngologist.

"Sinus headache" is a common complaint in the otolaryngology office. Recent literature has shown that the majority of patients with this complaint satisfy the diagnostic criteria for migraine. This review article presents an overview of the sinus headache literature, with emphasis on the incidence, identification, and treatment of migraine headache for the otolaryngologist.

Gelstat Migraine (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase.

BACKGROUND: Treatment of migraine headaches is often delayed due to assessing the potential severity of an evolving headache or anticipating unwanted consequences from prescription medication. Studies have demonstrated improved pain-free response when prescription treatments are taken during the mild headache phase of a migraine. This study was designed to evaluate the efficacy of an OTC product, GelStat Migraine, when taken in the early, mild pain phase of migraine. MATERIAL/METHODS: An open-label study enrolling 30 subjects, male and female, with a one-year history of migraine meeting IHS diagnostic criteria with or without aura, 2-8 migraines per month and < or = 15 headache days per month. Inclusion required having migraines that consistently started at mild and worsened to moderate or severe, if untreated, in at least 75% of attacks. Subjects also had to be able to distinguish migraine from non-migraine headaches and reliably identify migraine early in the course of an attack. One headache was treated in the mild pain phase with GelStat Migraine, a combination of feverfew and ginger. RESULTS: 29 evaluable subjects completed the study, all treating at mild pain. Two hours after treatment, 48% were pain-free with 34% reporting a headache of only mild severity. 29% reported a recurrence within 24 hours. Side effects were minimal and not serious. 59% of subjects were satisfied with Gelstat Migraine therapy and 41% preferred GelStat Migraine or felt it was equal to their pre-study medication. CONCLUSIONS: GelStat Migraine is effective as a first line abortive treatment for migraine when initiated early during the mild headache phase.

Sinus headache: a neurology, otolaryngology, allergy, and primary care consensus on diagnosis and treatment.

Sinus headache is a widely accepted clinical diagnosis, although many medical specialists consider it an uncommon cause of recurrent headaches. The inappropriate diagnosis of sinus headache can lead to unnecessary diagnostic studies, surgical interventions, and medical treatments. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to define conditions that lead to headaches of rhinogenic origin but have done so from different perspectives and in isolation of each other. An interdisciplinary ad hoc committee convened to discuss the role of sinus disease as a cause of headache and to review recent epidemiological studies that suggest sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. This committee reviewed available scientific evidence from multiple disciplines and concluded that considerable research and clinical study are required to further understand and delineate the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, this group agreed that greater diagnostic and therapeutic attention needs to be given to patients with sinus headaches.

Cosensitization of pain and psychiatric comorbidity in chronic daily headache.

Chronic migraine occurs in approximately 20% of migraineurs, typically developing over a period of many years. The pathophysiology of this transformation is unknown. However, experts have associated chronic headache with analgesic overuse, physical injury, and psychologic trauma. Research in post-traumatic stress disorder has found that hippocampal sensitivity to stress alters and often amplifies future pain behaviors. Although the most obvious difference between migraine and chronic migraine is the frequency of headaches, this article discusses chronic migraine as a more pervasive neurologic disease in which the patient's neurologic and psychologic function fails to return to a normal baseline. The sensory and affective components of pain are cosensitized, producing other neurologic and psychologic symptoms during and between episodes of headache. A staging paradigm is suggested that defines patients and assesses their overall neurologic function. The goal of this classification is to identify cosensitization early and pinpoint migraine patients who are at risk of developing chronic migraine.

Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache.

BACKGROUND: Symptoms referable to the sinus area are frequently reported during migraine attacks, but are not recognized in diagnostic criteria. Underrecognition of migraine may be partly attributed to a variable clinical presentation, and migraines with "sinus" symptoms contribute to this problem. This study was conducted to determine the prevalence of migraine-type headache (International Headache Society [IHS]-defined migraine without aura [IHS 1.1], migraine with aura [IHS 1.2], or migrainous disorder [IHS 1.7]) in patients with a history of self-described or physician-diagnosed "sinus" headache. METHODS: During a clinic visit, patients with a history of "sinus" headache, no previous diagnosis of migraine, and no evidence of infection were assigned an IHS headache diagnosis on the basis of headache histories and reported symptoms. RESULTS: A total of 2991 patients were screened. The majority (88%) of these patients with a history of self-described or physician-diagnosed "sinus" headache were diagnosed at the screening visit as fulfilling IHS migraine criteria (80% of patients) or migrainous criteria (8% of patients). The most common symptoms referable to the sinus area reported by patients at screening were sinus pressure (84%), sinus pain (82%), and nasal congestion (63%). CONCLUSIONS: In this study, 88% of patients with a history of "sinus" headache were determined to have migraine-type headache. In patients with recurrent headaches without fever or purulent discharge, the presence of sinus-area symptoms may be part of the migraine process. Migraine should be included in the differential diagnosis of these patients.

A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine.

BACKGROUND: Menstrually associated migraine (MAM) is often prolonged and difficult to manage with conventional therapies. Frovatriptan is a new selective 5HT(1B/1D) receptor agonist indicated for short-term management of migraine. It has a long half-life and good tolerability. These characteristics suggest that frovatriptan may be useful for the intermittent prevention of MAM. METHODS: The study was a randomized, double-blind, placebo-controlled, three-way crossover design. Patients treated each of three perimenstrual periods (PMPs) with placebo, frovatriptan 2.5 mg QD, and frovatriptan 2.5 mg BID. The 6-day treatment started 2 days before the anticipated start of MAM headache. The primary efficacy endpoint was incidence of MAM headache during the 6-day PMP. RESULTS: The population comprised 546 women (mean age, 37.6 years). Use of frovatriptan reduced the occurrence of MAM headache. The incidence of MAM headache during the 6-day PMP was 67% for placebo, 52% for frovatriptan 2.5 mg QD, and 41% for frovatriptan 2.5 mg BID. Both frovatriptan regimens were superior to placebo (p < 0.0001), and the BID regimen was superior to the QD regimen (p < 0.001). Both frovatriptan regimens also reduced MAM severity (p < 0.0001), duration (p < 0.0001), and the use of rescue medication (p < 0.01 QD; p < 0.0001 BID) in a dose-dependent manner. The incidence and type of adverse events for both regimens were similar to placebo and consistent with those reported for short-term migraine management. CONCLUSION: Frovatriptan given prophylactically for 6 days was effective in reducing the incidence of menstrually associated migraine. More than half of patients who used frovatriptan 2.5 mg BID had no menstrually associated migraine headache during the 6-day perimenstrual period. The findings are consistent with the long duration of action and good tolerability of frovatriptan observed in short-term migraine management.

The pathophysiology of primary headache.

Headache research has been a productive area, and understanding of primary headache pathophysiology has increased greatly. There are many more questions that need to be answered to gain a better understanding of the primary headache process. For the clinician,there is value in understanding the pathophysiology of primary headache, because this understanding can help improve diagnostic acumen and shape treatment plans to provide patients with more effective treatment.

Understanding the patient with migraine: the evolution from episodic headache to chronic neurologic disease. A proposed classification of patients with headache.

Traditionally, episodic primary headache disorders are characterized by a return of preheadache (normal) neurologic function between episodes of headache. In contrast, patients with chronic headache often do not return to normal neurologic function between headache attacks. This article proposes that the evolution from episodic migraine to chronic headache may parallel the neurologic disruption observed during the progression of an acute migraine attack and that changes in baseline neurologic function between episodes of headache may be a more sensitive indicator of headache transformation than headache frequency alone. Early recognition of nonheadache changes in nervous system function may offer a more sensitive and specific approach to migraine prevention.

Sinus headache: a clinical conundrum.

The concept of sinus disease as a common cause of headache is deeply ingrained in the American public, but there is little evidence to support the sinuses as a common cause of disabling headache. On the other hand, a body of evidence supports the concept that migraine can present with facial pain and nasal symptoms such as congestion and rhinorrhea. In clinical studies nearly 90% of participants with self-diagnosed or physician-diagnosed sinus headache met criteria for IHS migraine-type headache and responded to triptan interventions in a manner similar to that witnessed in migraine. Consequently it is likely that most individuals seeking medical attention for sinus headache are, in fact, experiencing migraine. Nasal pathologic conditions, however, can also cause sinus headache. In general. other symptoms in addition to headache are also present, but there is clear symptom overlap among migraine, rhinosinusitis, and other nasal passage/sinus pathologic conditions, and further research is needed.

Building a migraine toolkit for patients: successful management of migraine headache.

Management of migraine headache had once been considered as one of the least satisfying conditions to treat. Fortunately, developments in our understanding of the disorder and available treatment options have revolutionized therapy and greatly improved outcomes of affected patients. Two major factors are the development of a treatment "toolkit" for patients and a mutual setting of goals by the patient and clinician. The treatment "toolkit" includes several very important elements, foremost among them is patient education. This critical component provides a logical basis of therapy by helping patients understand the disorder and aiding deployment of the toolkit. This knowledge empowers patients to optimize treatment outcome and minimize the headache-related disability that drives them to seek treatment. Setting of goals for both acute and preventive care, providing behavioral and lifestyle advice, offering appropriate medications for acute attacks and headache prevention, and incorporating strategies for effective use enhance success. Monitoring outcome can focus the management and help more patients attain effective care rapidly. Employing such an approach can turn therapy into a process that proves to be satisfying to both patient and clinician.