Objective: Assess the effects of rimegepant on quality of life (QoL) over 1-year of open-label treatment in which rimegepant was used for both preventive and acute treatment for migraine. Background: Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of migraine. Design/Methods: This open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) enrolled adults aged ≥18 years with a history of 4–18 moderate to severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day could continue with open-label treatment with rimegepant 75 mg for 52 weeks of preventive treatment. On nonscheduled dosing days, subjects could take open-label rimegepant 75 mg as needed up to once per day for acute treatment of migraine. The effects of rimegepant on QoL were measured using Migraine-Specific Quality-of-Life Questionnaire v 2.1 (MSQ) scores on the role restrictive (RR), role preventative (RP), and emotional function (EF) domains. Changes from baseline in MSQ domain scores were assessed at Weeks 12 and 52 of the open-label phase (ie, overall study Weeks 24 and 64). Higher MSQ scores indicated better quality of life. Results: Respective mean (SD) baseline MSQ scores for the RR, RP, and EF domains were 51.0 (18.70), 65.2 (21.01), and 57.7 (27.23). At Week 12 (n=536) mean (SD) changes from baseline in RR, RP, and EF, respectively, were 28.4 (22.71), 21.8 (21.46), and 27.4 (26.58); at Week 52 (n=398), they were 32.9 (21.46) for RR, 25.1 (21.66) for RP, and 30.1 (26.40) for EF. Conclusions: Long-term treatment with oral rimegepant 75 mg taken every other day for preventive treatment and up to once daily on nonscheduled days as needed for acute treatment was associated with improvements in migraine-specific QoL. Disclosure: Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan, Amgen, Novartis, Teva, Lilly, Lundbeck, Biohaven,Impel. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen, Teva, Allergan, Biohaven, Lilly, Lundbeck, Theranica, Revance. Dr. Turner has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Allergan, Amgen, Biohaven, Teva, Novartis, Lundbeck, Lilly. The institution of Dr. Turner has received research support from Allergan, Amgen, Biohaven, Lilly, Lundbeck, Theranica. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck . Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lundbeck. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for lilly. The institution of Dr. Winner has received research support from Amgen. The institution of Dr. Winner has received research support from Allergan. The institution of Dr. Winner has received research support from Lundbeck . The institution of Dr. Winner has received research support from Novartis. The institution of Dr. Winner has received research support from Lilly. The institution of Dr. Winner has received research support from Teva. The institution of Dr. Winner has received research support from Supernus. The institution of Dr. Winner has received research support from Biogen. The institution of Dr. Winner has received research support from Avinar. The institution of Dr. Winner has received research support from SAMUS. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has received stock or an ownership interest from biohaven pharmaceuticals. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

OBJECTIVE:We sought to evaluate temporal response patterns to erenumab treatment in patients with episodic migraine. BACKGROUND:Although many patients treated with erenumab experience onset of efficacy as early as 1 week, clinical benefits of migraine preventive therapies may accrue with continued treatment. Furthermore, details about the maintenance of clinical responses have not been reported. METHODS:This was a post hoc analysis of a 6-month, randomized, double-blind, placebo-controlled, phase 3 study of erenumab for the prevention of episodic migraine. We analyzed temporal responses to erenumab using a threshold of ≥50% reduction from baseline in monthly migraine days (MMDs). RESULTS:During the 6-month treatment period, 73.7% (230/312) and 79.6% (253/318) of patients in the erenumab 70 mg (n = 312) and 140 mg (n = 318) groups, respectively, achieved a response in at least 1 month. In this group of responders, at least half reached first monthly response (first month with ≥50% reduction from baseline in MMDs) by month 2 and at least 75% of them by month 3. The remainder responded in months 4-6. Of patients in the erenumab 70 and 140 mg groups, 35.3% (110/312) and 41.8% (133/318), respectively, responded over months 1-3 (mean response over first 3 months). Of these patients, 81.8% (90/110) and 81.9% (109/133) maintained this response over months 4-6 (mean response over last 3 months) in the 70 and 140 mg groups, respectively. Many patients who did not achieve an initial response (≥50% reduction from baseline in MMDs during month 1) responded later with continued treatment, with approximately one-half or more of initial nonresponders responding by months 4-6. CONCLUSIONS:These results support guidelines recommending at least 3 months following the initiation of erenumab for migraine prevention before the assessment of response.

Migraine involves brain hypersensitivity with episodic dysfunction triggered by behavioral or physiological stressors. During an acute migraine attack the trigeminal nerve is activated (peripheral sensitization). This leads to central sensitization with activation of the central pathways including the trigeminal nucleus caudalis, the trigemino-thalamic tract, and the thalamus. In episodic migraine the sensitization process ends with the individual act, but with chronic migraine central sensitization may continue interictally. Increased allostatic load, the consequence of chronic, repeated exposure to stressors, leads to central sensitization, lowering the threshold for future neuronal activation (hypervigilance). Ostensibly innocuous stressors are then sufficient to trigger an attack. Medications that reduce sensitization may help patients who are hypervigilant and help to balance allostatic load. Acute treatments and drugs for migraine prevention have traditionally been used to reduce attack duration and frequency. However, since many patients do not fully respond, an unmet treatment need remains. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in nociception and in the sensitization of peripheral and central neurons of the trigeminovascular system, which is implicated in migraine pathophysiology. Elevated CGRP levels are associated with dysregulated signaling in the trigeminovascular system, leading to maladaptive responses to behavioral or physiological stressors. CGRP may, therefore, play a key role in the underlying pathophysiology of migraine. Increased understanding of the role of CGRP in migraine led to the development of small-molecule antagonists (gepants) and monoclonal antibodies (mAbs) that target either CGRP or the receptor (CGRP-R) to restore homeostasis, reducing the frequency, duration, and severity of attacks. In clinical trials, US Food and Drug Administration-approved anti-CGRP-R/CGRP mAbs were well tolerated and effective as preventive migraine treatments. Here, we explore the role of CGRP in migraine pathophysiology and the use of gepants or mAbs to suppress CGRP-R signaling via inhibition of the CGRP ligand or receptor. Migraine is a neurological disease affecting one in eight people. Symptoms include nausea and/or sensitivity to light and sound, and a throbbing headache. Although certain genes may increase the likelihood of migraine, environmental stimuli and molecules that increase the sensitivity of brain blood vessels and their innervations also play a role. During a migraine attack, nerves in the brain are activated, leading to increased sensitivity to stimuli, lowering the future threshold for activation, and making patients hypervigilant. Chronic, repeated exposure to certain stimuli can also lower this activation threshold, such that relatively innocuous stimuli can trigger an attack. Excessive use of certain migraine treatments can increase headache frequency over time and produce unwanted side effects; thus, selective agents are needed that specifically target the systems and pathways affected in migraine pathophysiology. Calcitonin gene-related peptide (CGRP), produced and released by nerve cells, is important in migraine pathophysiology. CGRP binds smooth muscle cell receptors, dilating blood vessels supplying the brain, and also binds to peripheral nerve cells that transmit pain signals to the spinal cord and brain. CGRP levels are elevated during a migraine attack. Medications targeting the CGRP pathway may decrease sensitivity and potentially normalize responses in hypervigilant patients. Two commercially available oral drugs that block CGRP receptors (‘gepants’) have reduced symptoms during migraine attacks in clinical trials. Four monoclonal antibodies (proteins that bind a specific molecule) have also been developed that target CGRP or the receptor and have been shown to significantly reduce the number of migraine days per month.

The standard of care in the treatment of migraine is to completely stop the migraine attack without medication adverse effects as well as to stop current disability and thereby prevent chronification.1 The goal of preventive therapy is to decrease headache frequency, duration and intensity of migraine producing less disability, and preventing progression. Over the past 3 years, headache experts have seen the rapid and extraordinary efficacy and tolerability of calcitonin generelated peptide (CGRP) monoclonal antibodies (mAbs) and gepants. These agents are safe, tolerable, and have a proven track record, which led to FDA approval. Headache experts must be able to choose— after discussion with the patient— the therapy that is most appropriate. For example, comorbid uncontrolled hypertension and frequent migraine attacks requires prevention and control of blood pressure possibly with a betablocker or candesartan. The patient with highfrequency migraine and depression could be treated with preventive venlafaxine. Gepants are as effective as triptans. Gepants are not vasoconstrictors, do not cause medication overuse headache, and have fewer adverse effects. Rimegepant can work acutely and preventively. Patients seek rapid improvement without side effects. They can be offered treatment with CGRP mAbs and as needed gepants as a first option. It is unethical and a breach of headache management to state clinicians should try two preventives first for 2– 3 months before using CGRP mAbs. Eight to twelve weeks of suffering is not appropriate or good medicine. The CGRP mAbs work within 1 week and are highly effective overall without severe highfrequency adverse effects.2 To state that we should try the older oral preventives first because they are cheaper is misdirected economics as it ultimately leads to more expense, and it is not good headache medicine. As acute care agents, the gepants are as effective as the triptans with fewer adverse effects. Rimegepant is the only agent that is currently FDA labeled for both acute and preventive treatment of migraine. The Hepp et al. study has demonstrated that adherence rates of the older preventative medications are between 26% and 29% at 6 months and 17% and 20% at 12 months.3 In the longterm extension study of fremanezumab, only 4% discontinued due to adverse effects and 4% discontinued due to lack of efficacy.4 At 1 year in a study on episodic migraine, 9.8% discontinued erenumab, 6.5% due to subject request, 2% due to loss of followup, 1.2% due to protocolspecific criteria, and 0.1% due to death.5 Although insurance company policies can be set by internal decisionmaking, the insurance companies have copied and pasted the AHS consensus statements: (1) Use two triptans before prescribing a gepant and (2) Use two oral preventives first before using CGRP mAbs. These step therapies delay and prohibit the approval for gepants and CGRP mAbs as firstline therapy. The few comments in this AHS document recognizing physician discretion and judgment are not recognized by the insurance carriers. Cost considerations is not a goal of treatment. Our task is to treat our patients with effective therapies that are safe and without adverse effects, not cheap drugs first. We are clinicians, not economists. The authors of the AHS consensus state in clinical settings, the incidence of adverse events with CGRP mAbs may be higher than in clinical trials. However, the Kanaan et al. study validated the findings of benefit of erenumab observed in clinical trials. Although adverse events were far more common in this population than in clinical trials, the planned continuation rate was relatively high (in comparison with the dismal adherence rates of the cheaper oral drugs in the Hepp et al. study).6 Remote electrical neuromodulation is FDA approved for the acute treatment of migraine in adolescents, not for preventive therapy. The authors of the AHS consensus statement acknowledge the faster response of the CGRP mAbs and yet they advise (and have transmitted to the insurance companies) to use two oral drugs before CGRP mAbs because of “cost considerations.” In conclusion, the authors of the AHS consensus should recommend the following: (1) Remove the two triptans before a gepant and two oral preventive medications for 2– 3 months before using a CGRP mAbs. Leave decisions about proper therapy up to the clinician and patient and do not give the insurance companies a weapon to block proven therapies chosen by the clinician and the patient. (2) Delete the incorrect statement that remote electrical neuromodulation was approved for preventive therapy in adolescence.

Saturday, April 25April 14, 2020Free AccessRimegepant 75 mg Is More Effective for Migraine Than Nonsteroidal Anti-inflammatory Drugs: Post Hoc Analysis of Data From 2 Phase 3 Trials (2107)Ira Turner, Dawn Buse, Andrew Blumenfeld, Elyse Stock, David Stock, Charles Conway, Christopher Jensen, Beth Morris, Vladimir Coric, and Robert CroopAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.2107 Letters to the Editor

Introduction/Objective: Chronic migraine (CM) is associated with impaired health-related quality of life and substantial socioeconomic burden, but many people with CM are underdiagnosed and do not receive appropriate preventive treatment. OnabotulinumtoxinA and topiramate have demonstrated efficacy (treatment benefit under ideal conditions) for the prevention of headaches in people with CM in clinical trials, but real-world studies suggest markedly different clinical effectiveness (treatment benefit based on a blend of efficacy and tolerability). This study sought to evaluate patient-reported outcomes (PROs) of onabotulinumtoxinA versus topiramate immediate release for people with CM. Methods: FORWARD was a prospective, multicenter, randomized, parallel-group, open-label, phase 4 study comparing onabotulinumtoxinA 155 U every 12 weeks with topiramate 50 to 100 mg/day for ≤36 weeks in people with CM. PROs measured included the Headache Impact Test (HIT-6), 9-item Patient Health Questionnaire Quick Depression Assessment (PHQ-9), Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), and Functional Impact of Migraine Questionnaire (FIMQ). Results: A total of 282 patients were randomized and treated with onabotulinumtoxinA (n = 140) or topiramate (n = 142). From baseline to week 30, mean HIT-6 test scores improved significantly in patients taking onabotulinumtoxinA compared with topiramate ( P < .001). Improvements in depression over time were observed via larger changes in PHQ-9 scores with onabotulinumtoxinA than topiramate ( P < .001). Work productivity assessed via WPAI:SHP scores revealed significant improvements with onabotulinumtoxinA versus topiramate in Work Productivity Loss ( P = .024) and Activity Impairment ( P < .001) domains. Results from the FIMQ also revealed a larger reduction from baseline with onabotulinumtoxinA vs topiramate ( P < .0001). Conclusion: OnabotulinumtoxinA treatment had more favorable real-world effectiveness than topiramate on depression, headache impact, functioning and daily living, activity, and work productivity. The overall study results suggest that the beneficial effects on a range of PROs are the result of improved effectiveness when onabotulinumtoxinA is used as preventive treatment for CM. Trial Registration: ClinicalTrials.gov: NCT02191579; https://clinicaltrials.gov/ct2/show/NCT02191579

Background Migraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine. Methods Analyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN: N = 1113). Patients were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. Safety and PK data included additional phase 2 and phase 3 trials for a larger sample size of patients > 60 years (range = 18–65 for all studies). Subgroup analyses assessed efficacy measures, adverse event (AE) occurrence, and cardiovascular measurement changes by patient age group. Galcanezumab PK were evaluated using a population analysis approach, where age was examined as a potential covariate on apparent clearance (CL/F) and apparent volume of distribution (V/F) of galcanezumab. Results Numbers of baseline monthly migraine headache days were similar across age groups. There were no statistically significant treatment-by-age group interactions for any efficacy measures, except in episodic migraine studies where older patients appeared to have a larger reduction than younger patients in the number of monthly migraine headache days with acute medication use. Age (18–65) had a minimal effect on CL/F, and no effect on V/F. Galcanezumab-treated patients ≥60 years experienced no clinically meaningful increases in blood pressure and no increased frequency in treatment-emergent AEs, discontinuations due to AEs, serious adverse events (SAEs) overall, or cardiovascular SAEs, compared to age-matched placebo-treated patients. Conclusions Age (up to 65 years) does not affect efficacy in migraine prevention and has no clinically meaningful influence on galcanezumab PK to warrant dose adjustment. Furthermore, older galcanezumab-treated patients experienced no increases in frequency of AEs or increases in blood pressure compared with age-matched placebo-treated patients. Trial registrations EVOLVE-1 ( NCT02614183 , registered 23 November 2015), EVOLVE-2 ( NCT02614196 , 23 November 2015), REGAIN ( NCT02614261 , 23 November 2015), ART-01 ( NCT01625988 , 20 June 2012, ), I5Q-MC-CGAB ( NCT02163993 , 12 June 2014, ), I5Q-MC-CGAJ ( NCT02614287 , 23 November 2015, ), all retrospectively registered.

BackgroundWe studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine.MethodsSAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50mg (SPARTAN only), 100mg, 200mg, or placebo. Study drug was to be taken within 4 hours (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2h and took a second dose 2-24h post-first dose) or recurrence (patient pain-free at 2h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan.ResultsThe proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p>0.05); MBS free, 71% vs 41% (p=0.02); pain relief, 77% vs 52% (p=0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo.ConclusionsA second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

ObjectivesTo investigate the factors that influence a migraineur's beliefs regarding oral triptans for the acute treatment of migraines and to provide further insight into patients' decision‐making process when faced with migraine.MethodsA multicenter, cross‐sectional, observational study of subjects currently prescribed an oral triptan medication for the acute treatment of migraine headaches. Subjects were recruited from 6 headache clinics and one primary care practice in the United States. Enrolled subjects completed a questionnaire that could be completed either at the site as part of the visit or at home. The questionnaire comprised 27 questions assessing demographic characteristics, migraine history, migraine frequency and severity, and general beliefs about migraine treatments. The study population was stratified into 2 cohorts (Early Treatment and Delayed Treatment) based on how they typically use their oral triptan to treat a typical migraine.ResultsA total 506 subjects were enrolled in the study, of which 502 were stratified into the Early Treatment cohort (41.2%) and Delayed Treatment cohort (58.8%). Demographic and clinical characteristics were generally similar between the 2 cohorts. In terms of general treatment patterns, there were notable differences between the Delayed and Early Treatment cohorts, with the Delayed Treatment cohort significantly more likely to take an over‐the‐counter (OTC) or non‐triptan medication first (P ≤ .001) and only take a triptan if the OTC or non‐triptan medication did not work (P ≤ .001). Furthermore, 55% of the Delayed Treatment cohort delayed taking a triptan to be certain that the headache was a migraine (vs 32% of the Early Treatment cohort; P ≤ .001). When asked to specify the reasons for delaying treatment with a triptan, the Delayed Treatment cohort had, in general, greater concerns about using their oral triptan in comparison with the Early Treatment cohort. In particular, respondents were primarily concerned with running out of their triptan medication with 35% of the Delayed Treatment cohort expressing this concern compared with 22% of the Early Treatment cohort (P ≤ .001). Statistically significant differences were also noted for concerns about taking medications (P ≤ .001), side effects (P ≤ .05), expense (P ≤ .01), and taking prescription medications (P ≤ .001).ConclusionsResults build upon previously published studies and suggest that patient beliefs directly influence how migraineurs manage their migraines and have implications for patient outcomes. Such insights should be used to facilitate physician–patient communication and reinforce the need for patient‐centered care to improve patient outcomes.

ObjectiveTo determine if baseline/interictal saliva calcitonin gene‐related peptide (CGRP) levels would be lower in subjects with chronic migraine receiving onabotulinumtoxinA compared with those receiving saline.BackgroundCGRP is considered central to the pathogenesis of episodic migraine, but its relationship to chronic migraine is less understood. OnabotulinumtoxinA is an effective treatment for chronic migraine and has been demonstrated to inhibit the vesicular release of CGRP.MethodsThis was an exploratory, randomized, placebo‐controlled, crossover pilot study of 20 subjects that received onabotulinumtoxinA and saline injection (placebo). The amount of CGRP in saliva samples collected on a nonheadache or low headache day, and prior to and after treatment of a headache exacerbation was measured. Daily headache records, medications, and response to treatment were recorded in a diary.ResultsA decrease in baseline/interictal saliva CGRP levels for subjects receiving onabotulinumtoxinA from 39.4 ± 7.5 pg CGRP/mg total protein after the first month to 25.5 ± 4.1 pg after the third month was observed. However, this difference did not reach significance nor was it significant when compared to the saline treatment. There was a reduction in the number of headache days for both onabotulinumtoxinA and saline over baseline throughout the active phases of the study. However, there was no statistical difference in headache days between groups. Subjects with a greater than 50% response to onabotulinumtoxinA had better 2‐hour pain relief with acute treatment than non‐responders to onabotulinumtoxinA or saline.ConclusionWhile CGRP levels were not elevated during a migraine attack in chronic migraine subjects as has been reported in episodic migraine, there was an overall decrease in the baseline/interictal levels in response to onabotulinumtoxinA.

(Headache 2011;51:961‐970)Objective.— To investigate a broad definition of migraine resolution that extends beyond specific migraine‐associated diagnostic symptoms as measured by the Completeness of Response Survey.Methods.— Conducted at 8 sites, 135 subjects treated migraines with SumaRT/Nap over 2 months. To measure subjects' experiences with SumaRT/Nap compared to their usual migraine medication, the Headache Impact Test, Revised Patient Perception of Migraine Questionnaire, and Completeness of Response Survey were administered at baseline and at 2 months.Results.— The effects of the study medicine compared to the subjects' usual migraine medicine reached statistical significance in decreasing headache severity, lessening of associated symptoms, and attaining complete relief with a single dose (60.04% of attacks resolved at 2 hours post‐treatment).Conclusion.— Compared to a subject's usual treatment, SumaRT/Nap used early and consistently for treatment of acute migraine offers important clinical improvements, including lessening of associated symptoms beyond International Headache Society criteria.