Acute Medication Use Research Articles

One-Year Compliance After Calcitonin Gene-Related Peptide Monoclonal Antibody Therapy for Migraine Patients in a Real-World Setting: A Multicenter Cross-Sectional Study

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a breakthrough migraine treatment, but long-term compliance under limited public insurance coverage has not been well known. This study explores one-year treatment patterns and outcomes of CGRP mAbs using real-world data. Methods: This multicenter retrospective study included migraine patients treated with CGRP monoclonal antibodies (CGRP mAbs) from July 2022 to June 2023. Treatment discontinuation was defined as a gap of over 60 days between injections. Among patients with 12 months of follow-up, adherence was measured using the Proportion of Days Covered (PDC), calculated as the ratio of days covered to the follow-up duration, with PDC ≥ 80% indicating good adherence. Efficacy was also assessed, defined as a ≥50% reduction in monthly headache days and acute medication use. Results: The study included 140 patients (mean age 44.6 ± 12.1 years; 82.9% female). Migraine without aura was predominant (93.6%), and 65.0% had chronic migraine. CGRP mAbs discontinuation occurred in 71.4% of patients, primarily due to headache improvement (22.9%) or lack of efficacy (15.0%). Among 81 patients with 12 months of follow-up, good adherence was observed in 40.7% of patients. Among these patients, 60.6% achieved a ≥50% reduction in monthly headache days, and 51.9% showed a ≥50% reduction in monthly acute medication use. Conclusions: More than two-thirds of patients discontinued the CGRP mAb within 1 year, so these findings emphasize the need for strategies to improve adherence and optimize follow-up plans to enhance patient support.

Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care.

Background/Objectives: Medication-overuse headache (MOH) is a disabling condition affecting patients with chronic migraine resulting from excessive use of acute headache medication. It is characterized by both pain modulation and addiction-like mechanisms involving the brainstem raphe, a region critical to serotonergic signaling. This study investigates whether alterations in the brainstem raphe, assessed via transcranial sonography (TCS), are associated with MOH and independent of depressive symptoms, aiming to explore their utility as a biomarker. Methods: This prospective case-control study included 60 migraine patients (15 with MOH) and 7 healthy controls. Comprehensive clinical and psychometric assessments were performed to evaluate headache burden, medication use, and depressive symptoms. TCS was used to assess brainstem raphe echogenicity, with findings analyzed using generalized linear models adjusted for depression. Results: Non-visibility of the brainstem raphe was significantly associated with MOH, with an unadjusted odds ratio (OR) of 6.88 (95% CI: 1.32-36.01, p = 0.02). After adjusting for depressive symptoms, this association remained significant, with an adjusted OR of 1.85 (95% CI: 1.02-3.34, p = 0.041). TCS demonstrated good intraclass correlation, highlighting its reproducibility and ability to detect changes relevant to MOH pathophysiology. Conclusions: Brainstem raphe alterations are associated with MOH and may serve as a potential biomarker for its diagnosis and management. TCS offers a non-invasive, cost-effective tool for identifying MOH-specific mechanisms, which could improve clinical decision-making and support personalized care in chronic headache disorders. Further studies are needed to validate these findings and refine the clinical applications of brainstem-focused diagnostics.

An evolving machine-learning-based algorithm to early predict response to anti-CGRP monoclonal antibodies in patients with migraine.

The present study aimed to determine whether machine-learning (ML)-based models can predict 3-, 6, and 12-month responses to the monoclonal antibodies (mAbs) against the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRPmAbs) in patients with migraine using early predictors (up to one month) and to create an evolving prediction tool. In this prospective cohort study, data from patients with migraine who had received anti-CGRP mAbs for 12 months were collected. Demographic and monthly clinical variables were collected, including monthly headache days (MHDs), days with acute medication use, number of analgesics and Headache Impact Test-6. Response rates were categorized as <25%, 26-50%, 51-75% and >75% reduction in MHDs. ML models were trained using random forest algorithm and optimized to maximize the F1 score. ML model performance was also evaluated using standard evaluation metrics, including accuracy, precision and area under the receiver operating characteristic curve (AUC-ROC). Sequential backward feature selection was employed to identify the most relevant predictors for each model. Each model was given 11 baseline data inputs and month-based predictors for months 1, 3 and 6. Each model was then validated against an external test cohort of patients who had received anti-CGRP mAbs for 12 months. Three hundred thirty-six patients treated with anti-CGRP mAbs were included. The external cohort included 93 patients treated with anti-CGRP mAbs. We developed six models to predict 3- 6- and 12-month responses using early predictors. ML-based models yielded predictions with an accuracy score in the range 0.40-0.73 and an AUC-ROC score in the range 0.56-0.76 during internal testing and yielding predictions with an accuracy in the range 0.39-0.64 and an AUC-ROC score in the range 0.52-0.78 when tested against an external test cohort. Shapley Additive explanations summary plots were generated to interpret the contribution of each feature for each model. Based on these findings, a response prediction tool was developed. Each model was run through a backward feature selection to find the most relevant features for the models. The MHDs reduction of the previous data point tends to be the most relevant, while the migraine with aura indicator tends to be the least effective predictor. The response prediction tool utilizing evolving ML-based models holds promise in the early prediction of treatment outcomes for patients with migraine undergoing anti-CGRP mAbs treatment.

Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis.

Background: Migraine is a common neurological condition marked by unilateral recurrent pulsating headaches, often associated with systemic signs and symptoms. Recently, calcitonin gene-related peptide (CGRP) antagonists, including atogepant, an oral CGRP receptor antagonist, have emerged as effective and safe treatments. The current study sought to assess the efficacy and safety of atogepant for preventing episodic migraines in adults. Methods: A comprehensive search, following PRISMA guidelines, was conducted using PubMed, Web of Science, and Cochrane Library to identify randomized, double-blind, placebo-controlled trials published up to June 2024. Results: The studies included adult participants with episodic migraine treated with atogepant. The primary outcomes assessed were changes in mean monthly migraine days (MMDs) and monthly headache days (MHDs) over 12 weeks. Secondary outcomes included reduction in acute medication use, 50% responder rates, and adverse events. A meta-analysis using a random-effects model was performed to evaluate efficacy and safety. Six trials with 4569 participants were included. Atogepant significantly reduced mean monthly migraine days (MMDs) and monthly headache days (MHDs) compared to placebo at all doses (10 mg, 30 mg, 60 mg), with the 60 mg dose showing the greatest reduction (mean difference: -1.48 days, p < 0.001). Significant reductions in acute medication use and improved 50% responder rates were also observed for all doses. The safety profile of atogepant was favorable, with common adverse events being mild to moderate, such as constipation and nausea. There were no significant differences in serious adverse events between the atogepant and placebo groups. Conclusions: Atogepant is an effective and well-tolerated option for preventing episodic migraines, showing significant reductions in migraine frequency and acute medication use. However, further studies are necessary to assess its long-term safety and efficacy, especially at higher doses, and to investigate its potential role in personalized treatment strategies for migraine prevention.

Long-term reductions in acute headache medication use after eptinezumab treatment in patients with migraine and prior preventive treatment failures: Post hoc analysis of the DELIVER randomized trial.

To evaluate long-term reductions in acute headache medication (AHM) use with eptinezumab versus placebo in patients with prior preventive migraine treatment failures and medication overuse (MO). Preventive migraine treatment is recommended for patients for whom AHMs have failed and for those who are using excessive amounts of AHM. MO may worsen headache and migraine symptoms in people with migraine; it is a risk factor for disease chronification and/or MO headache. DELIVER was a multicenter, parallel-group, double-blind, randomized, placebo-controlled, phase 3b clinical trial that randomized adults with migraine and two to four prior preventive failures to eptinezumab 100 mg, 300 mg, or placebo infusion every 12 weeks; patients initially given placebo received eptinezumab 100 mg or 300 mg in the extension period. MO was defined according to diagnostic criteria for MO headache in the baseline diary reports. This post hoc analysis of the DELIVER study included change from baseline in AHM days/month of use (ergotamines, triptans, simple or combination analgesics, and opioids; total and select class-specific use) in the MO population. A total of 890 patients were included in the total population, and 438/890 (49.2%) had MO at baseline. In both the total population and MO population, eptinezumab resulted in greater reductions in total AHM days/month of use during weeks 1-24 than placebo, with triptans showing the largest reduction among AHM classes. Patients switching from placebo to eptinezumab experienced reductions in AHM days/month similar to that of initial eptinezumab treatment. In the extension population, mean (standard error [SE]) changes from baseline in AHM days/month were -4.6 (0.32; 100 mg) and -4.8 (0.32; 300 mg) across weeks 1-4 in patients who received eptinezumab for the entire treatment period and were -4.8 (0.44; placebo-100 mg) and -5.5 (0.44; placebo-300 mg) across weeks 25-28 in patients who switched from placebo to eptinezumab. Mean (SE) changes from baseline in AHM days/month in the extension MO population were -6.5 (0.59; 100 mg) and -6.6 (0.57; 300 mg) across weeks 1-4 in patients who received eptinezumab for the entire treatment period and were -7.1 (0.81; 100 mg) and -8.0 (0.80; 300 mg) across weeks 25-28 in patients who were switched from placebo to eptinezumab. All treatment arms sustained or further reduced AHM use across 18 months of trial participation. Across weeks 1-4, in patients fulfilling criteria for MO at baseline, 68.0% (102/150) of patients treated with eptinezumab 100 mg and 74.7% (109/146) of patients treated with eptinezumab 300 mg reported AHM use below MO thresholds compared to 43.3% (61/141) of patients receiving placebo. In patients with MO at baseline, the proportion of patients without MO remained above 60.0% for all treatment groups during the extension period. Eptinezumab reduced total AHM use more than placebo in patients with prior preventive failures and in patients with MO at baseline; largest reductions were observed for triptans. Robust reductions in AHM use after eptinezumab were sustained or further reduced with up to 18 months of treatment, and most patients no longer met thresholds for MO.

Exploring the multifaceted characteristics of aura in migraine: A multicenter, cross-sectional study.

Migraine with aura (MwA) is a debilitating disorder characterized by paroxysmal attacks of pain preceded or accompanied by reversible neurological symptoms. While the pathophysiology remains unclear, trigeminovascular system activation and cortical spreading depression have been implicated. This study aims to comprehensively investigate and characterize the diverse clinical features and manifestations of aura, as well as the types of acute medications self-administered for aura management. A multicenter, cross-sectional study was conducted using data from the Italian Headache Registry (RICe). Aura characteristics, frequency, duration and associated migraine premonitory symptoms were collected. Acute medication use and timing (headache or aura phase) were assessed. The study included 272 patients with a diagnosis of MwA. Most patients (99.3%) experienced typical aura symptoms, with visual aura (96.3%) being the most prevalent, followed by sensory (33.0%) and speech and/or language aura (25.6%). Brainstem aura (8.5%) and motor aura (1.8%) were less common. Notably, 13.0% of patients reported aura relapses within 24 hours. Triptans (39.7%), non-steroidal anti-inflammatory drugs (47.8%) and nutraceuticals (59.9%) were commonly used for acute aura management. This study reports several different aura manifestations, highlighting atypical features, aura relapse rates and treatment approaches for aura. These findings could contribute to a deeper understanding of aura and its management in clinical settings.

Public Knowledge and Attitude of Caregivers Regarding Leftover Medications for Children under 6 Years of Age in Japan: A Descriptive Study on a Nationwide Exploratory Questionnaire Survey to Caregivers.

Leftover medications are a global concern for harm to health and inadequate medical care costs. However, information on leftover medicines and their inappropriate use in children in Japan is lacking. We aimed to clarify the proportion of leftover and re-use of children's medications in Japan. We conducted a nationwide cross-sectional questionnaire survey using eight web-based domains, which covered parents' demographics, children's demographics, actual practices in handling about leftover (1) acute medication, (2) chronic medication, (3) short-term medicine, (4) antibiotic, and (5) topical medication, and attitudes towards leftover medicine. The questionnaire comprised 40 questions. We obtained responses from 3046 caregivers with children aged under 6 years before elementary school. Among these participants, 95% (2674/2809), 57% (147/256), and 69% (1687/2457) had experience with leftover acute medication use, medication for chronic disease, and short-term medication use, respectively. Instances of leftover antibiotics being given to the child's brother/sister, parents, and child's friends were 8.7, 7.9, and 3.2%, respectively. This trend was similar to other medication categories. In conclusion, most caregivers have experienced leftover medications; however, managing leftover medications depends on their beliefs and is influenced by inadequate knowledge about medications. Most of these cases lead to inadequate use of medications in children. Medical staff, especially pharmacists, need to educate and instruct caregivers on the appropriate use of children's medications.

Acupuncture Treatment for Chronic Post-Traumatic Headache in Individuals with Mild Traumatic Brain Injury: A Pilot Study.

Chronic post-traumatic headache (CPTH) after a mild traumatic brain injury (mTBI) has been reported in up to 60% of patients and can be extremely debilitating. While pharmacological treatments are typically used for CPTH, they frequently cause side effects and have limited effectiveness, leading individuals with CPTH to be unsatisfied with current treatment options and to seek nonpharmacological options. Acupuncture has been identified as a potential treatment option; however, the evidence in this population remains limited. The overall goal of this study was to examine the effect of a once weekly (e.g., low dose) versus twice weekly (e.g., high dose) of acupuncture treatment on CPTH in individuals with mTBI. Thirty-eight individuals were randomized to receive either 5 or 10 acupuncture treatments using a standard protocol over 5 weeks. The protocol consisted of 14 points using traditional acupuncture and 4 points using electroacupuncture. Headache outcomes, safety, treatment adherence, sleep quality, and quality of life (QOL) were assessed. The results showed that while there were no differences between dose groups for any of the outcomes assessed, acupuncture significantly reduced the number of headache days and headache pain intensity in individuals with CPTH. There were no significant changes in acute medication use or sleep quality. While there were some QOL improvements identified, these results should be interpreted with caution. Overall, acupuncture was shown to be safe and well-tolerated in people with CPTH after mTBI, and five acupuncture treatments using a standardized protocol shows promise in providing headache relief for this population.

Prospective study of risk factors for community-acquired acute kidney injury

Background and hypothesisCauses and risk factors for community-acquired acute kidney injury (CA-AKI) have not been thoroughly studied. The aim of this study was to examine the risk factors for CA-AKI. MethodsIn this prospective study, we examined serum creatinine from all individuals visiting a university hospital's emergency department (ED) over an 11-month period for the presence of AKI defined according to the KDIGO criteria. Patients with AKI were invited to participate. Randomly selected controls (1:2) were paired according to age, sex, and date of admission. Participants answered questions about their medical history and medication use, including over-the-counter (OTC) drugs. Conditional logistic regression was used to identify factors associated with AKI. ResultsOf 602 AKI cases identified, 512 participated in the study. AKI cases were significantly more likely than controls to have used nonsteroidal anti-inflammatory drugs (NSAIDs) (26.0 % vs 18.0 %, p = 0,001) in the week preceding the ED visit, particularly OTC NSAIDs (23.3 % vs 15.9 %, p < 0.001). AKI was associated with a recent history of vomiting (OR 2.52 [95 %CI 1.87–3.39]), diarrhea (1.30 [1.00–1.70]) and urinary retention (1.92 [1.36–2.72]), use of non-selective NSAIDs (1.84, [1.37–2.48]), RAAS blockers (1.63 [1.21–2.19]), and diuretics (1.53 [1.13–2.08]), and a history of diabetes (1.42 [1.04–1.94]), CKD (1.36 [1.01–1.83]) and smoking (1.72 [1.24–2.37]). ConclusionsEvents in the setting of acute illness and medication use, including OTC NSAIDs, may play a greater role in the development of CA-AKI than comorbid conditions. Frequent use of OTC NSAIDs is a concern and should be addressed in view of serious adverse effects.

Changes in Use of Migraine Medications, Healthcare Resource Utilization, and Associated Direct Costs Over 12Months Following Initiation of Erenumab: A US Retrospective Real-World Analysis.

Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab. We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or < 80% of days covered (non-adherent). Outcomes were measured pre- and post-index, and differences between these periods were described. Among 7528 eligible patients, the mean (standard deviation) age was 45.1 (11.4) years and 85.4% were female; 38.5% of patients were adherent to erenumab. Most patients used acute or traditional migraine-preventive medications pre-index, with reductions in use observed post-index (acute medication was used by 95.6% of patients pre-index, compared to 92.3% post-index; traditional preventive medication was used by 89.6% of patients pre-index, compared to 81.9% post-index). Reductions were observed for HRU of emergency room visits (-3.8%) and brain- and other head-imaging studies (-7.5%). Overall costs associated with acute and traditional preventive medications were reduced (-$764), but costs for HRU increased slightly ($76). When stratifying by adherence and combining costs for acute and traditional preventive medications and HRU, adherent patients had cost decreases (-$1947), while non-adherent patients had cost increases ($101). Most patients initiating erenumab had prior use of acute and traditional migraine-preventive therapies. The reduction in acute and traditional migraine-preventive medication use and HRU over the 12-month follow-up supports the long-term clinical benefits of erenumab in the real-world setting.

Ubrogepant users' real-world experience: Patients on ubrogepant, characteristics and outcomes (UNIVERSE) study.

To assess the real-world effectiveness of ubrogepant by evaluating self-reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real-world effectiveness of ubrogepant. The UNIVERSE study was an observational, cross-sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30-question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant. Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post-dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function. Ubrogepant demonstrated real-world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication.

Medication-Overuse Headache: Update on Management.

Long-term frequent use of acute pain medication for the treatment of headaches has paradoxically been shown to increase the frequency of headaches. So-called medication-overuse headache (MOH) is particularly problematic in patients with migraine who overuse triptans and opioids. Prevention through education remains the most important management strategy. Once established, MOH can be difficult to treat. Although complete or near-complete withdrawal of acute pain medication for 8-12 weeks has been shown to benefit most patients, this can be hard to achieve. The use of OnabotulinumtoxinA and drugs that target the calcitonin gene-related peptide system for the prevention of migraines have been shown to benefit patients with MOH. Furthermore, the use of novel acute pain medication for migraines, including Gepants and Ditans, which do not cause MOH, are likely to improve patient outcomes. In this review article we examine the following: the burden of MOH; who develops MOH; the pathophysiological mechanisms; and the treatment strategies.

Changes in use of acute and preventive medications for migraine after erenumab initiation over 12 months: A United States retrospective cohort study.

To assess changes in real-world use of acute and preventive medications for migraine over a 12-month follow-up period in the United States following initiation of the anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab. Early assessments of real-world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow-up. This retrospective cohort study used data from the IQVIA open-source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified. Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12-month pre-index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti-CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre-index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post-index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12-month follow-up period. Similarly, among 173,225 patients with pre-index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post-index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12-month follow-up period. In this long-term study, we observed the discontinuation of both acute and preventive medications for migraine post-erenumab initiation.

Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial.

To describe exploratory endpoints from a previous phase 2b/3 placebo-controlled trial conducted in Japan and Korea, specifically investigating the effect of fremanezumab or placebo on migraine-associated symptoms and acute headache medication use in patients with episodic migraine (EM). EM is associated with non-head pain symptoms, including nausea, vomiting, photophobia, or phonophobia, which contribute substantially to the disease burden, healthcare resource utilization, and impaired quality of life. Current EM treatments include a mix of nonspecific/migraine-specific acute headache medications, but medication overuse can induce headaches and progression from EM to chronic migraine (CM). In multiple phase 2b/3 trials, the monoclonal antibody fremanezumab significantly reduced the average number of monthly migraine days experienced by patients with EM/CM compared with placebo. This was a prespecified analysis of exploratory endpoints in a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial conducted in Japanese and Korean patients with EM (NCT03303092). Patients were randomized to receive fremanezumab, either monthly or quarterly, or matching placebo, administered subcutaneously at 4-week/28-day ("monthly") intervals to maintain blinding. Exploratory endpoints reported here were the mean change from baseline in the number of days/month with (i) the use of any acute headache medication, (ii) the use of any migraine-specific acute headache medication, (iii) nausea or vomiting, and (iv) photophobia and phonophobia. Overall, 357 Japanese and Korean patients with EM received either monthly (n = 121) or quarterly (n = 119) fremanezumab or placebo (n = 117). Compared with placebo, fremanezumab administered monthly or quarterly was associated with a significant reduction from baseline in the average number of days/month with acute headache medication use over three months (difference vs. placebo -2.81 [95% confidence interval (CI) -3.52, -2.11]; p < 0.001 and -2.79 [95% CI -3.50, -2.08]; p < 0.001, respectively). Similar findings were observed in the monthly average number of days with migraine-specific acute headache medications (difference vs. placebo with monthly and quarterly fremanezumab, -2.63 [95% CI -3.31, -1.95] for both; p < 0.001), the average number of days/month with nausea or vomiting (difference vs. placebo -1.09 [95% CI -1.60, -0.58]; p < 0.001 for monthly fremanezumab and -1.37 [95% CI -1.88, -0.86]; p < 0.001 for quarterly fremanezumab), and the average number of days with photophobia and phonophobia (difference vs. placebo -1.22 [95% CI -1.80, -0.65]; p < 0.001 and -1.64 [95% CI -2.22, -1.06]; p < 0.001, respectively). Monthly and quarterly administered fremanezumab effectively prevented EM in Japanese and Korean patients. Fremanezumab also improved other disease aspects including the need for acute headache medications and the frequency of migraine-associated symptoms.

Efficacy of Desvenlafaxine in Reducing Migraine Frequency and Severity: A Retrospective Study.

Background: Migraine is characterized by sudden acute episodes of pain, with a global prevalence of 18% among all age groups. It is the second leading cause of years lived with disability worldwide. Prophylactic treatment is important in managing migraine; however, its efficacy and safety are debated. This study aimed to evaluate the efficacy of desvenlafaxine in female patients with migraine. Methods: We conducted a retrospective observational case study involving 10 women diagnosed with migraine who were treated with desvenlafaxine. We measured the number of migraine days per month, average headache duration in minutes, headache severity using a visual analog scale, use of acute medications, and frequency of acute medication use per week. Results: Desvenlafaxine significantly reduced the number of migraine days from 14.70 ± 3.68 at baseline to 2.50 ± 2.50 at follow-up (p < 0.05). The average headache duration dropped from 131.25 ± 32.81 min to 52.50 ± 44.64 min. Headache severity scores improved from 6.80 ± 1.49 at baseline to 0.80 ± 0.92 at follow up, the frequency of acute medication use per week reduced from 3.30 ± 1.49 at baseline to 0.80 ± 0.92, and the frequency of acute medication use decreased from 3.30 ± 1.49 times per week to 0.80 ± 0.92. Conclusions: Desvenlafaxine shows potential as an effective prophylactic therapy for migraine. Larger-scale studies are necessary to further explore its benefits.

Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies.

Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients' disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients. These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database. Patients were required to have ≥ 12 months of continuous enrollment in medical and pharmacy benefits prior to index (baseline) and after index (follow-up). Patients were stratified into chronic migraine (CM) and non-chronic migraine (non-CM) by diagnosis codes. Based on acute migraine-specific medication dispensing data in the follow-up period, non-CM patients were divided into 3 cohorts: highest, middle, and lowest tertile of total units of dispensed acute migraine-specific medication (gepants, ditans, ergot derivatives, and triptans). Migraine medication use was captured in the baseline and follow-up periods. A total of 22,584 CM and 216,807 non-CM patients (72,269 patients in each tertile) were identified and included in the study. Over the follow-up, CM patients had a mean of 70 units of acute migraine-specific medications dispensed, while the highest, middle, and lowest tertile of non-CM patients had a mean of 92, 29, and 10 units, respectively. Anti-calcitonin gene-related peptide pathway mAbs were dispensed for 28.9% of CM patients, and for 6.9%, 4.1%, and 2.9% of non-CM patients in the highest, middle, and lowest tertiles, respectively. A lower proportion of non-CM patients had use of anti-calcitonin gene-related peptide pathway mAbs compared to CM patients, confirming the unmet need with appropriate preventive medication. There appears to be a persistent gap in management of patients without a diagnosis of CM who are dispensed high quantities of acute migraine-specific medications.

Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial.

Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse. This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures. Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse. Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs. ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137. This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

Use of medications for migraine in Aotearoa New Zealand.

To document and assess acute and preventive medication use in people with migraine disease in Aotearoa New Zealand. Online survey of people with migraine in Aotearoa New Zealand (n=530), run from 22 August to 7 October 2022, including questions on current and previous acute and preventive medication use, reasons for medication discontinuation and use of new migraine medications. Most respondents had used simple analgesics for acute treatment; 55% were currently using a triptan; 27% were currently using an opioid. Overall, 27% of survey respondents had over-used at least one acute medication in the last month. Half of respondents were taking at least one preventive medication but only 57% of those eligible for preventive treatment were currently taking it. In those who had previously tried preventives, side effects and lack of efficacy were common reasons for stopping. Cost, lack of knowledge and awareness were the main barriers to use of new migraine medications. Many people with migraine in Aotearoa New Zealand are not receiving optimal treatment, which increases the burden and cost of migraine disease. More effective and tolerable acute and preventive medications are needed that are affordable and available in Aotearoa New Zealand. Greater awareness of best practice prescribing is also needed.

Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis

BackgroundMigraine is one of the most common diseases worldwide while current treatment options are not ideal. New therapeutic classes of migraine, the calcitonin gene-related peptide (CGRP) antagonists, have been developed and shown considerable effectiveness and safety. The present study aimed to systematically evaluate the efficacy and safety of atogepant, a CGRP antagonist, for migraine prophylaxis from the results of randomized controlled trials (RCTs).MethodsThe Cochrane Library, Embase, PubMed and https://www.clinicaltrials.gov/ were searched for RCTs that compared atogepant with placebo for migraine prophylaxis from inception of the databases to Feb 1, 2024. Outcome data involving efficacy and safety were combined and analyzed using Review Manager Software version 5.3 (RevMan 5.3). For each outcome, risk ratios (RRs) or standardized mean difference (SMD) were calculated.Results4 RCTs with a total of 2813 subjects met our inclusion criteria. The overall effect estimate showed that atogepant was significantly superior to placebo in terms of the reduction of monthly migraine (SMD − 0.40, 95% CI -0.46 to -0.34) or headache (SMD − 0.39, 95% CI -0.46 to -0.33) days, the reduction of acute medication use days (SMD − 0.45, 95% CI -0.51 to -0.39) and 50% responder rate (RR 1.66, 95% CI 1.46 to 1.89), while no dose-related improvements were found between different dosage groups. For the safety, significant number of patients experienced treatment-emergent adverse events (TEAEs) with atogepant than with placebo (RR 1.10, 95% CI 1.02–1.21) while there was no obvious difference between the five dosage groups. Most TEAEs involved constipation (RR 2.55, 95% CI 1.91–3.41), nausea (RR 2.19, 95% CI 1.67–2.87) and urinary tract infection (RR 1.49, 95% CI 1.05–2.11). In addition, a high dosage of atogepant may also increase the risk of treatment-related TEAEs (RR 1.64, 95% CI 1.02–2.63) and fatigue (RR 3.07, 95% CI 1.13–8.35).ConclusionsThis meta-analysis suggests that atogepant is effective and tolerable for migraine prophylaxis including episodic or chronic migraine compared with placebo. It is critical to weigh the benefits of different doses against the risk of adverse events in clinical application of atogepant. Longer and multi-dose trials with larger sample sizes are required to verify the current findings.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.