Migraine Preventive Medications Research Articles

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function. The objective of this analysis was to assess changes in MFIQ scores following initiation or modification of migraine preventive medication and determine if changes in function are associated with changes in other aspects of migraine burden, such as headache frequency, headache intensity, and symptoms of anxiety and depression. This is a secondary analysis of data from the Medication Overuse Treatment Strategy (MOTS) trial, a prospective pragmatic clinical trial that investigated two treatment strategies for those with chronic migraine and medication overuse. Data from both treatment arms were pooled and analyzed using a pre-post design. Prior to and 12 weeks following initiation or modification of migraine preventive medication, participants completed a series of questionnaires that captured migraine characteristics, medication use, migraine-related physical impairment (MFIQ), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire 9 [PHQ-9]) symptoms. Changes from baseline in all measures were assessed using the paired t-test. Relationships between changes in MFIQ scores and other measures were assessed using linear regression. Multivariable modeling was performed to determine which additional variables contributed to the change in MFIQ beyond that already explained by an individual variable. Model terms were selected by using elastic net regularization. Only those participants who completed the baseline and 12-week MFIQ were included in this analysis. Of the 537 patients, 88.2% were female, and the average age was 45 years (standard deviation 13). The mean frequency of days with moderate-to-severe headache improved 39.2% from 13.5 per 30 days at baseline to 8.1 per 30 days at week 12. The mean MFIQ Usual Activities Global score improved by 15.0 points (on a 100-point scale). All five domains (Usual Activities Global, Usual Activities, Social Function, Emotional Function, Physical Function) of the MFIQ improved by a mean of at least 13.0 points. Changes in PHQ-9 score, followed by changes in headache frequency, had the strongest associations with change in all domains of the MFIQ. The negative impact of chronic migraine with medication overuse on physical, social, and emotional functioning substantially lessened following initiation or modification of migraine preventive medication. Improved functioning, as measured by the MFIQ, was most strongly associated with reductions in depression scores and headache frequency, highlighting the importance of recognizing and monitoring changes in depressive symptoms, in addition to headache frequency and functional impairment, when evaluating response to preventive medications.

Characterizing gaps in the preventive pharmacologic treatment of migraine: Multi-country results from the CaMEO-I study.

To analyze data from the Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study in order to characterize preventive medication use and identify preventive usage gaps among people with migraine across multiple countries. Guidelines for the preventive treatment of migraine are available from scientific organizations in various countries. Although these guidelines differ among countries, eligibility for preventive treatment is generally based on monthly headache day (MHD) frequency and associated disability. The overwhelming majority of people with migraine who are eligible for preventive treatment do not receive it. The CaMEO-I Study was a cross-sectional, observational, web-based panel survey study performed in six countries: Canada, France, Germany, Japan, the United Kingdom, and the United States. People were invited to complete an online survey in their national language(s) to identify those with migraine according to modified International Classification of Headache Disorders, 3rd edition, criteria. People classified with migraine answered questions about current and ever use of both acute and preventive treatments for migraine. Available preventive medications for migraine differed by country. MHD frequency and associated disability data were collected. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment (i.e., ≥3 monthly MHDs with severe disability, ≥4 MHDs with some disability, or ≥6 MHDs regardless of level of disability). Among 90,613 valid completers of the screening survey, 14,492 met criteria for migraine and completed the full survey, with approximately 2400 respondents from each country. Based on the AHS consensus statement preventive treatment candidacy algorithm, averaging across countries, 36.2% (5246/14,492) of respondents with migraine qualified for preventive treatment. Most respondents (84.5% [4431/5246]) who met criteria for preventive treatment according to the AHS consensus statement were not using a preventive medication at the time of the survey. Moreover, 19.3% (2799/14,492) of respondents had ever used preventive medication (ever users); 58.1% (1625/2799) of respondents who reported ever using a preventive medication for migraine were still taking it. Of the respondents who were currently using a preventive medication, 50.2% (815/1625) still met the criteria for needing preventive treatment based on the AHS consensus statement. Most people with migraine who qualify for preventive treatment are not currently taking it. Additionally, many people currently taking preventive pharmacologic treatment still meet the algorithm criteria for needing preventive treatment, suggesting inadequate benefit from their current regimen.

Patient Reluctance as a Possible Barrier to Taking Migraine Preventive Medications: Results of the OVERCOME (US) Study (P2-12.004)

Patient Reluctance as a Possible Barrier to Taking Migraine Preventive Medications: Results of the OVERCOME (US) Study (P2-12.004)

Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop

Background Chronic migraine is a disabling condition that can substantially impact on quality of life. People with chronic migraine have headaches on at least 15 days of every month. Preventative medications aiming to reduce number of days with migraine are available, but high-quality randomised evidence is lacking for many drugs, and it is unclear which medications should be prioritised for research. There is also no existing evidence about patient and clinicians’ priorities for research. Methods We undertook a consensus workshop with patient and healthcare professional stakeholders, using nominal group technique, to understand these stakeholders’ priorities for future randomised controlled trials. We reached a consensus on a set of research recommendations for the field. Results Eight people with chronic migraine and eleven healthcare professionals took part in an online workshop. Comparisons of calcitonin gene-related peptide monoclonal antibodies (CGRP MAbs) and OnabotulinumtoxinA (BTA) were a top priority for our group. Candesartan and Flunarizine were the top drugs the group wanted to compare against placebo. Conclusions These research recommendations should guide researchers in the field, and funders when prioritising commissioned research and assessing funding applications. Particular areas to explore further are Candesartan or Flunarizine versus placebo, and comparing and combining CGRP MAbs with other medications.

Medication "underuse" headache.

Many risk factors have been associated with migraine progression, including insufficient and ineffective utilization of migraine medications; however, they have been inadequately explored. This has resulted in suboptimal usage of medications without effective altering of prescribing recommendations for patients, posing a risk for migraine chronification. Our aim is to conduct a comprehensive review of the available evidence regarding the underuse of migraine medications, both acute and preventive. The term "underuse" includes, but is not limited to: (1) ineffective use of appropriate and inappropriate medication; (2) underutilization; (3) inappropriate timing of usage; and (4) patient dissatisfaction with medication. The underuse of both acute and preventive medications has been shown to contribute to the progression of migraine. In terms of acute medication, chronification occurs as a result of insufficient drug use, including failure of the prescriber to select the appropriate type based on pain intensity and disability, patients taking medication too late (more than 60 minutes after the onset or after central sensitization has occurred as evidenced by allodynia), and discontinuation because of lack of effect or intolerable side effects. The underlying cause of inadequate effectiveness of acute medication lies in its inability to halt the propagation of peripheral activation to central sensitization in a timely manner. For oral and injectable preventive migraine medications, insufficient efficacy and intolerable side effects have led to poor adherence and discontinuation with subsequent progression of migraine. The underlying pathophysiology here is rooted in the repetitive stimulation of afferent sensory pain fibers, followed by ascending brainstem pain pathways plus dysfunction of the endogenous descending brainstem pain inhibitory pathway. Although anti-calcitonin gene-related peptide (CGRP) medications partially address pain caused by the above factors, including decreased efficacy and tolerability from conventional therapy, some patients do not respond well to this treatment. Research suggests that initiating preventive anti-CGRP treatment at an early stage (during low frequency episodic migraine attacks) is more beneficial than commencing it during high frequency episodic attacks or when chronic migraine has begun. The term "medication underuse" is underrecognized, but it holds significant importance. Optimal usage of acute care and preventive migraine medications could potentially prevent migraine chronification and improve the treatment of migraine attacks.

A large language model-based generative natural language processing framework fine-tuned on clinical notes accurately extracts headache frequency from electronic health records.

To develop a natural language processing (NLP) algorithm that can accurately extract headache frequency from free-text clinical notes. Headache frequency, defined as the number of days with any headache in a month (or 4 weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional NLP algorithms. This was a retrospective cross-sectional study with patients identified from two tertiary headache referral centers, Mayo Clinic Arizona and Mayo Clinic Rochester. All neurology consultation notes written by 15 specialized clinicians (11 headache specialists and 4 nurse practitioners) between 2012 and 2022 were extracted and 1915 notes were used for model fine-tuning (90%) and testing (10%). We employed four different NLP frameworks: (1) ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model, (2) Generative Pre-Trained Transformer-2 (GPT-2) Question Answering (QA) model zero-shot, (3) GPT-2 QA model few-shot training fine-tuned on clinical notes, and (4) GPT-2 generative model few-shot training fine-tuned on clinical notes to generate the answer by considering the context of included text. The mean (standard deviation) headache frequency of our training and testing datasets were 13.4 (10.9) and 14.4 (11.2), respectively. The GPT-2 generative model was the best-performing model with an accuracy of 0.92 (0.91, 0.93, 95% confidence interval [CI]) and R2 score of 0.89 (0.87, 0.90, 95% CI), and all GPT-2-based models outperformed the ClinicalBERT model in terms of exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy of 0.27 (0.26, 0.28), it demonstrated a high R2 score of 0.88 (0.85, 0.89), suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2 score was higher than the GPT-2 QA zero-shot model or GPT-2 QA model few-shot training fine-tuned model. We developed a robust information extraction model based on a state-of-the-art large language model, a GPT-2 generative model that can extract headache frequency from EHR free-text clinical notes with high accuracy and R2 score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT-2-based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT-2 generative model and inference code with open-source license of community use in GitHub. Additional fine-tuning of the algorithm might be required when applied to different health-care systems for various clinical use cases.

Early Use of Erenumab vs Nonspecific Oral Migraine Preventives

Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. ClinicalTrials.gov Identifier: NCT03927144.

Treatment patterns of galcanezumab versus standard of care preventive migraine medications over 24 months: a US retrospective claims study

Objective To describe long-term (24-month) treatment patterns of patients initiating galcanezumab versus standard of care (SOC) preventive migraine treatments including anticonvulsants, beta-blockers, antidepressants, and onabotulinumtoxinA using administrative claims data. Methods This retrospective cohort study, which used Optum de-identified Market Clarity data, included adults with migraine with ≥1 claim for galcanezumab or SOC preventive migraine therapy (September 1, 2018 − March 31, 2020) and continuous database enrollment for 12 months before (baseline) and 24 months after (follow-up) the index date (date of first claim). Baseline patient demographics, clinical characteristics, and treatment patterns were analyzed after 24-month follow-up, including adherence (measured as the proportion of days covered [PDC]), persistence, discontinuation (≥60-day gap), restart, and treatment switch. Propensity score matching (1:1) was used to balance the galcanezumab and SOC cohorts. Results The study included 2307 matched patient pairs with 24-month follow-up. The mean age across cohorts was 44.5 years (females: ∼87%). Patients in the galcanezumab versus SOC cohort demonstrated greater treatment adherence (PDC: 48% vs. 38%), with more patients considered adherent (PDC ≥80%: 26.6% vs. 20.7%) and persistent (322.1 vs. 236.4 d) (all p < .001). After 24-month follow-up, fewer galcanezumab-treated patients had discontinued compared with SOC-treated patients (80.1% vs. 84.7%; p < .001), of which 41.3% and 39.6% switched to a non-index medication, respectively. The most prevalent medication patients switched to in both cohorts was erenumab. Significantly greater proportions of patients who initiated galcanezumab versus SOC medications switched to fremanezumab (p < .001) and onabotulinumtoxinA (p = .016). Conclusion Patients who initiated galcanezumab for migraine prevention had higher treatment adherence and persistence compared with those who initiated SOC medications after 24-month follow-up.

Preventive treatment patterns in the adult migraine population: an observational UK study over 7 years

BackgroundCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are recommended by the United Kingdom National Institute of Health and Care Excellence for the prevention of migraine as treatment beyond third line. We report migraine prevalence and preventive treatment patterns in the adult United Kingdom primary care population over a 7.5-year period, focusing on patients ceasing ≥ 3 oral preventive medication classes.MethodsStudy populations were retrieved from the Clinical Practice Research Datalink GOLD database (study period: 19 September 2012 to 1 January 2020; inclusion criteria: ≥12 months follow-up, current-in-dataset, adult on 1 January 2020). Patients who used ≥ 1 oral preventive medication with ≥ 3-year follow-up after first prescription were considered preventive treatment users; class cessation was defined as cessation without evidence of restart within 6 months from end-of-supply date.ResultsOn 1 January 2020, 3.0% of the total study population were diagnosed with migraine (n = 81,190/2,664,306); of these, 42.4% were preventive treatment users (n = 34,448/81,190). The most frequently used oral migraine preventive medication classes were beta-blockers (n = 14,713), tricyclic antidepressants (n = 14,415) and antiepileptics (n = 6497). Among preventive treatment users, 7.7% (n = 2653/34,448) ceased ≥ 3 oral preventive medication classes; of these, 21.7% (n = 576/2653) had been referred to a neurologist.ConclusionsCompared to existing population-based estimates of migraine prevalence, our data further corroborates that a considerable proportion of patients with migraine do not seek treatment. Among those who sought primary care within a 7.5-year period, almost half received empirical oral preventive treatment. Importantly, nearly 1 of 10 preventive treatment users ceased ≥ 3 oral preventive medication classes, highlighting a need for additional therapeutic options. These patients may benefit from CGRP antagonists and/or injectable onabotulinumtoxinA; however, only a minority was referred to specialist care, where these options would be more available.Trial RegistrationNot applicable.

Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review.

Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs. We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC). Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs. Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations. CRD42021265993.

MRI radiomics based machine learning model of the periaqueductal gray matter in migraine patients.

<p>The aim of the study was to investigate the question: Can MRI radiomics analysis of the periaqueductal gray region elucidate the pathophysiological mechanisms underlying various migraine subtypes, and can a machine learning model using these radiomics features accurately differentiate between migraine patients and healthy individuals, as well as between migraine subtypes, including atypical cases with overlapping symptoms?</p>. <p>The study analyzed initial MRI images of individuals taken after their first migraine diagnosis, and additional MRI scans were acquired from healthy subjects. Radiomics modeling was applied to analyze all the MRI images in the periaqueductal gray region. The dataset was randomized, and oversampling was used if there was class imbalance between groups. The optimal algorithm-based feature selection method was employed to select the most important 5-10 features to differentiate between the two groups. The classification performance of AI algorithms was evaluated using receiver operating characteristic analysis to calculate the area under the curve, classification accuracy, sensitivity, and specificity values. Participants were required to have a confirmed diagnosis of either episodic migraine, probable migraine, or chronic migraine. Patients with aura, those who used migraine-preventive medication within the past six months, or had chronic illnesses, psychiatric disorders, cerebrovascular conditions, neoplastic diseases, or other headache types were excluded from the study. Additionally, 102 healthy subjects who met the inclusion and exclusion criteria were included.&nbsp;</p>. <p>The algorithm-based information gain method for feature reduction had the best performance among all methods, with the first-order, gray-level size zone matrix, and gray-level co-occurrence matrix classes being the dominant feature classes. The machine learning model correctly classified 82.4% of migraine patients from healthy subjects. Within the migraine group, 74.1% of the episodic migraine-probable migraine patients and 90.5% of the chronic migraine patients were accurately classified. No significant difference was found between probable migraine and episodic migraine patients in terms of the periaqueductal gray region radiomics features. The kNN algorithm showed the best performance for classifying episodic migraine-probable migraine subtypes, while the Random Forest algorithm demonstrated the best performance for classifying the migraine group and chronic migraine subtype.</p>. <p>A radiomics-based machine learning model, utilizing standard MR images obtained during the diagnosis and follow-up of migraine patients, shows promise not only in aiding migraine diagnosis and classification for clinical approach, but also in understanding the neurological mechanisms underlying migraines.&nbsp;</p>.

Migraine-like headache in subjects with isolated Lambl’s excrescences: a case series and literature review

Aim Lambl’s excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl’s excrescences are associated with migraine. Methods Retrospective review of 182 inpatients with Lambl’s excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl’s excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits. Results A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl’s excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl’s excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications. Conclusions This study supports the hypothesis that microemboli from isolated Lambl’s excrescences could cause migraine-like headache. And intervention for Lambl’s excrescences may be crucial for preventing headache recurrence.

Treatment Patterns, Healthcare Resource Utilization, and Direct Costs Among Patients Initiating Concomitant Use of a Calcitonin Gene-Related Peptide Monoclonal Antibody (CGRP mAb) and Novel Acute Medication in the United States.

To describe treatment patterns, all-cause and migraine-related healthcare resource utilization (HCRU), and direct costs among people with migraine treated with concomitant calcitonin gene-related peptide monoclonal antibody (CGRP mAb) and novel acute migraine medications (ubrogepant, rimegepant, lasmiditan) in the United States (US). This retrospective, observational cohort study utilized data from the IBM MarketScan® Research Databases and included adults initiating CGRP mAb or novel acute migraine medication as index medications between May 01, 2018, and Feb 28, 2021. All-cause and migraine-related HCRU (number of visits) and costs at baseline (12 months pre-index) and at follow-up (12 months post-index) were descriptively analyzed; differences between values at follow-up and baseline were reported. Of 4,167 included in the analysis (mean [SD] age: 43.7 [11.2] years), 89.2% were women, and 59.7% had chronic migraine. Adherence to the indexed CGRP mAb was 47% (using proportion of days covered [PDC]) and 80.1% (using medication possession ratio [MPR]); mean (SD) persistence was 273.4 (115.3) days). At follow-up, 43.9% of the patients discontinued their index preventive medication of which 80.2% switched to a different preventive migraine medication; 17.0% restarted their index preventive medication. Reductions in all-cause inpatient HCRU, all-cause inpatient and outpatient costs, and migraine-related outpatient HCRU were observed at follow-up vs. baseline, whereas increases in all-cause outpatient HCRU, all-cause medication costs, migraine-related inpatient HCRU, and migraine-related inpatient, outpatient, and medication costs were observed. In this study, observed treatment patterns with the indexed CGRP mAb were consistent with prior reports. Concomitant treatment with CGRP mAb and novel acute migraine medications led to reductions in some outcomes of HCRU and direct costs, however, increases were also observed. Treatment utilization, reductions in HCRU and cost savings identified in this study in favor of concomitant CGRP mAb and novel acute medications may help clinicians and other healthcare decision makers assessing appropriate therapeutic options for migraine management.

Understanding the real-world treatment patterns in patients using migraine preventive medications in Ontario, Canada

Understanding the real-world treatment patterns in patients using migraine preventive medications in Ontario, Canada

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway

BackgroundNew acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs).MethodsIn this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period.ResultsOverall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period.ConclusionsMost patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication.Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Patterns of anti-CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy.

To describe the pattern of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) utilization in the Tuscany region, Italy, and the variation of triptan consumption after treatment initiation. Given the recent commercialization of anti-CGRP mAbs as migraine preventive medications, real-world evidence on their patterns of utilization and their impact on migraine abortive medication use is still limited. A retrospective, descriptive, cohort study on the real-world utilization of anti-CGRP mAbs was performed using the population-based regional administrative database of Tuscany. Patients with ≥1 anti-CGRP mAb dispensing (namely erenumab, galcanezumab, fremanezumab) between April 1, 2019, and September 30, 2021, were identified. The first dispensing was the cohort entry (CE). New users (NUs) were patients with no anti-CGRP mAb dispensing before CE. Kaplan-Meier (KM) curves were plotted to describe the cumulative probability of remaining with the initial anti-CGRP mAb during a 15-month follow-up period as a measure of treatment persistence. Among NUs with ≥2 triptan dispensings during the 6 months before CE (i.e., baseline), the mean monthly number of triptan dosage units dispensed was measured in five consecutive follow-up time windows (months 1-3, 4-6, 7-9, 10-12, 13-15) and the difference from the baseline was calculated. A total of 624 NUs (erenumab = 295, galcanezumab = 223, fremanezumab = 106) were identified, of whom 188 (78%) were women. Mean age was 49.2 years (standard deviation [SD] = 12.6). The survival to discontinuation at 6, 12, and 15 months was about 69%, 48%, and 6%, respectively. The survival to switch was about 6% at 15 months. The observed variation of triptan consumption at 3/6/9/12/15 months and the corresponding SD was -4.4 [8.2]/-5.2 [9.0]/-5.5 [9.2]/-5.4 [9.2]/-4.5 [10.0], respectively. Patient demographics reflect the place of these medications in therapy. Overall, findings seem to indicate a favorable tolerability and effectiveness profile. Further studies are warranted to better establish the long-term comparative effectiveness, safety, and cost effectiveness of anti-CGRP mAbs compared to other preventive medications.

Comparative Efficacy and Safety of Five Anti-Calcitonin Gene-Related Peptide Agents for Migraine Prevention: A Network Meta-Analysis.

Anti-Calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies (mAbs) for migraine prevention. In this network meta-analysis (NMA), the efficacy and safety of migraine treatments including different doses of atogepant and CGRP mAbs were evaluated to provide a reference for future clinical trials. A search using PubMed, Embase and Cochrane Library identified all randomized controlled trials (RCTs) published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias. In this study, 24 articles were considered for analysis. Regarding effectiveness, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225mg in change from baseline of migraine days (SMD=-0.49,95%CI[-0.62, -0.37]) and 50% response rate (RR=2.98,95%CI[2.16,4.10]), while the optimal choice for reducing acute medication days was monthly erenumab 140mg(SMD=-0.68,95%CI[-0.79, -0.58]). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240mg and quarterly fremanezumab 675mg. There was no significant difference in discontinuation due to AEs between interventions and placebo. All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225mg, monthly erenumab 140mg, and daily atogepant 60mg were effective interventions with fewer side effects.

Healthcare costs and resource utilization in patients with migraine treated with erenumab: A retrospective, non-interventional study using claims data from the United States.

To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States. This retrospective, non-interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017-9/1/2019) from the Komodo Health database. Outcomes included migraine-related and all-cause costs, use of other preventive/acute migraine medications, and HCRU. All outcomes were compared during the 180-day pre- versus the 180-day post-index periods. Cost outcomes were also assessed for longer periods including post-index Days 91-270 and monthly mean post-index costs for the longest time of continuous insurance enrollment. Overall, 1839 patients with migraine were included for analysis. Compared to the 180-day pre-index period, an increase in total migraine-related costs (+$2639; p < 0.0001), migraine-related prescription costs (+$3435, p < 0.0001), all-cause total costs (+$2977; p < 0.001), and all-cause prescription costs (+$4102; p < 0.0001) were observed during the 180-day post-index period after adjusting for covariates. Conversely, reduction in migraine-related medical costs (-$896; p < 0.0001), and significantly lower odds of migraine-related emergency room visits (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.44-0.82; p = 0.001), migraine-related office visits (OR 0.58, 95% CI 0.53-0.64; p < 0.0001), and migraine-related neurologist visits (OR 0.69, 95% CI 0.63-0.75; p < 0.0001) were observed during the 180-days post-index period. There were significant decreases in the odds of having overall preventive migraine medications (OR 0.81, 95% CI 0.75-0.87; p < 0.0001), acute-migraine medications (OR 0.92, 95% CI 0.85-1.00; p = 0.038), and triptan (OR 0.79, 95% CI 0.73-0.85; p < 0.0001) during the 180-day post-index period. Sensitivity analyses on cost outcomes found no statistically significant differences in pre-index migraine-related costs compared to post-index migraine-related costs when assessing longer post-index follow-up periods. Initiation of therapy with a novel treatment is often associated with an increase in overall healthcare costs due to the entrance costs associated with novel therapy. For a chronic condition such as migraine, cost versus health benefits should be evaluated over a long period (e.g., ≥2 years) to better understand the true benefits of therapy. Data from this study suggest that the entrance cost for erenumab, the primary driver of the high post-index prescription costs gets mitigated by reduced medical costs over long-term follow-up. The results indicate better disease management in adult patients with migraine, which should be an important consideration for both patients and payors, as these findings have shown an offset between migraine-related prescription and medical costs.

Burden and Unmet Needs in Migraine Patients: Results from the OVERCOME (Spain) Study.

This analysis aimed to evaluate demographics, migraine-related disability, symptoms, diagnosis and healthcare consultation, work productivity, and treatment patterns according to headache frequency in adults with migraine in the OVERCOME (ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE) (Spain) study. Data were obtained from an observational, cross-sectional, web-based survey conducted between October 2020-February 2021 in Spain. Eligible participants were adult members of online survey panels living in Spain who were able to read and write Spanish and fulfilled the International Classification of Headache Disorders, third edition (ICHD-3) criteria for migraine or had a self-reported physician diagnosis. In total, 10,229 patients comprised the Spanish sample. Only 56.2% of respondents had a confirmed healthcare professional (HCP) diagnosis of migraine, despite almost all meeting modified ICHD-3 criteria. Pain severity, migraine-related disability, and interictal burden increased with increasing number of headache days per month. Migraine impacted on respondents' work productivity, with increases in presenteeism, work productivity loss, and daily activity impairment at higher headache frequencies. Over the past year, 66.2% of all HCP visits were specifically due to migraine, most commonly with a general practitioner or pharmacist. A subgroup of 1277 patients (12.5% of the total survey population) met eligibility criteria for migraine preventive medications, of whom only 36.6% were currently taking a preventive. Results of the OVERCOME (Spain) survey reveal the substantial burden of migraine, which is directly linked to headache frequency. However, most patients experiencing frequent headaches and eligible for migraine preventives are currently not taking them. Findings highlight the importance of addressing unmet needs for people with migraine in Spain.

Episodic Migraine and Psychiatric Comorbidity: A Narrative Review of the Literature.

We evaluate the evolving evidence of psychiatric comorbidities associated with episodic migraine. Utilizing recent research publications, we aim to assess traditional treatment option considerations and discuss recent and evolving non-pharmacologic treatment progress for episodic migraine and related psychiatric conditions. Recent findings indicate that episodic migraine is strongly linked to comorbid depression, anxiety, posttraumatic stress disorder, and sleep disorders. Not only do patients with episodic migraine have higher rates of psychiatric comorbidity, but a higher number of headache days reported is also strongly linked to an increased risk of developing a psychiatric disorder, indicating there may be a link between frequency and psychiatric comorbidity and that patients with high-frequency episodic migraine should be assessed for psychiatric comorbidity. Few migraine preventive medications have examined the effect of the medication on both migraine and psychiatric comorbidity though we discuss what has been reported in the literature. Non-pharmacologic-based treatments including behavioral therapies and mind-body interventions previously developed for psychiatric conditions, e.g., mindfulness-based CBT (MBCT), acceptance and commitment therapy (ACT), and mindfulness-based stress reduction (MBSR) therapy, have promising results for patients diagnosed with episodic migraine and may therefore be useful in treating migraine and comorbid psychiatric conditions. Psychiatric comorbidity may affect the efficacy of the treatment of episodic migraine. Thus, we must assess for psychiatric comorbidities to inform better treatment plans for patients. Providing patients with episodic migraine with alternate modalities of treatment may help to improve patient-centered care and increase patients' sense of self-efficacy.