Cephalalgia最新文献

Background: Migraine is associated with obesity. These analyses evaluated weight change with atogepant used as a preventive migraine treatment.

Methods: Five atogepant clinical trials in adults with migraine (one phase 2b/3; four phase 3) were included: Three 12-week, randomized, placebo-controlled trials (episodic migraine: two; chronic migraine: one); one 40-week, open-label extension trial and one 52-week, standard care, randomized, long-term safety trial in episodic migraine. Change from baseline in body weight was measured.

Results: Mean baseline body mass indexes were 30.0-30.7 kg/m² (pooled episodic migraine [United States only]) and 25.0-25.5 kg/m² (chronic migraine [East Asia, Europe, and North America]). More participants treated with atogepant 60 mg once-daily compared to placebo experienced ≥7% weight loss at any time in the pooled episodic migraine placebo-controlled trials (4.9% vs. 2.8%), chronic migraine placebo-controlled trial (5.8% vs. 2.0%), and pooled open-label extension and long-term safety trials (24.0% vs.14.7% in standard care [long-term safety only]). In the placebo-controlled trials, weight loss with atogepant 60 mg once-daily was observed at week 2 (pooled episodic migraine: -0.32%; chronic migraine: -0.39%), increasing at week 12 (pooled episodic migraine: -1.02%; chronic migraine: -1.50%); compared to weight gain with placebo at week 12 (pooled episodic migraine: +0.49%; chronic migraine: +0.10%). In the long-term episodic migraine studies, weight loss with atogepant 60 mg once-daily was observed at week 4 (long-term safety: -0.42%; open-label extension: -0.76%), increasing at week 40 (long-term safety: -2.38%; open-label extension: -2.09%).

Conclusion: Atogepant was associated with modest dose- and duration-dependent weight loss.

Trial registration: ClinicalTrials.gov identifiers: NCT02848326 (CGP-MD-01); NCT03777059 (3101-301-002); NCT03700320 (long-term safety trial); NCT03939312 (open-label extension trial); NCT03855137 (3101-303-002).

Background: Despite the high prevalence of migraine in Europe, there is limited research on the burden among people with migraine.

Methods: This cross-sectional survey used patient-reported data from the 2020 European National Health and Wellness Survey in France, Germany, Italy, Spain, and the United Kingdom. The study assessed the sociodemographic characteristics, health-related quality of life, depression, work productivity and activity impairment, and healthcare resource utilization among matched samples of people with diagnosed migraine (n = 3985) and compared to a matched cohort without migraine (n = 7970). The study also analyzed the burden across migraine subgroups stratified by the number of migraine headache days.

Results: Lower health-related quality of life, higher depression, increased work productivity and activity impairment, and higher healthcare resource utilization were reported among people with migraine and ≥1 migraine headache days compared to matched people without migraine (all p < 0.001). Additionally, the incremental burden was also observed across migraine subgroups (1-3, 4-7, 8-14, and ≥15 migraine headache days) irrespective of the use of prescription medication compared to the matched controls without migraine.

Conclusion: Migraine sufferers with ≥1 migraine headache days experienced worse productivity, lower quality of life, depression, and increased healthcare resource utilization than those without migraine, emphasizing the need for effective management strategies.

Background: We aimed to assess the effects of preventive migraine treatment with atogepant vs. placebo on patient-reported quality of life and functioning.

Methods: Analyses of patient-reported outcomes from three 12-week, randomized, placebo-controlled trials evaluating preventive migraine treatment with atogepant 60 mg once-daily: ADVANCE (low-frequency episodic migraine [LFEM], 4-8 monthly migraine days [MMDs] and high-frequency episodic migraine [HFEM], 8-14 MMDs), PROGRESS (chronic migraine, CM) and ELEVATE (episodic migraine in those previously failed by two to four classes of oral preventive treatments).

Results: Least squares mean differences (95% confidence interval (CI)) in change from baseline were greater (p < 0.05) for atogepant vs. placebo for Migraine-Specific Quality of Life questionnaire Role Function-Restrictive domain scores at week 12 (ADVANCE: LFEM 12.0 (95% CI = 6.0-18.0), HFEM 9.9 (95% CI = 3.4-16.4); PROGRESS: 6.2 (95% CI = 2.5-9.8); ELEVATE: 17.7 (95% CI = 13.1-22.3)), for Headache Impact Test-6 total scores at week 12 (ADVANCE: LFEM -4.7 (95% CI = -6.7 to -2.7); HFEM -3.4 (95% CI = -5.5 to -1.2); PROGRESS: -2.8 (95% CI = -4.1 to -1.4); ELEVATE: -6.5 (95% CI = -8.3 to -4.7)) and for Activity Impairment in Migraine-Diary-Performance of Daily Activities scores across 12 weeks (ADVANCE: LFEM -2.3 (95% CI = -3.9 to -0.7), HFEM -4.5 (95% CI = -6.9 to -2.2); PROGRESS: -3.4 (95% CI = -5.3 to -1.5); ELEVATE: -4.7 (95% CI = -6.4 to -3.1)).

Conclusions: Preventive migraine treatment with atogepant 60 mg once-daily vs. placebo improved measures of migraine-related quality of life and functioning among participants with different headache frequencies and histories of previous treatment failure.Trial Registration: ClinicalTrials.gov: NCT03777059 (ADVANCE); NCT03855137 (PROGRESS); NCT04740827 (ELEVATE).

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: The anti-calcitonin gene-related peptide (CGRP), or its receptor (CGRP/R) monoclonal antibodies (mAbs), offer targeted, effective, and tolerated drugs for migraine. However, about 25% of patients fail to achieve a clinically meaningful response, usually leading to discontinuation. These patients often have a lengthy migraine history and multiple prior preventive treatment failures, resulting in limited therapeutic options. Herein, we describe the cause for and outcome of withdrawal of anti-CGRP/R mAb and evaluate the treatment course until discontinuation.

Methods: We conducted a prospective analysis on migraine patients attending the Florence Headache Center in Italy, who discontinued treatment with anti-CGRP/R mAbs. The primary objectives were to describe the reasons for anti-CGRP mAbs discontinuation and the treatment course. Secondary objectives were the evaluation of the absolute change from baseline in monthly headache days, response rates, persistence in medication overuse, absolute change from baseline of the overall number and days of analgesics use per month, change of MIDAS and HIT-6 at three, six, and 12 months, and the last month of treatment.

Results: Among 472 patients, 136 (28.8%) discontinued mAb treatment after an average of 9.0 ± 6.1 (mean ± SD) months. The majority (96/136, 70.6%) discontinued due to ineffectiveness, followed by lost to follow-up during treatment (18/136, 13.1%) and adverse events (10/136, 7.3%). In total, 77.9% of the 136 patients ceased treatment within the first year. Following discontinuation, 48.5% initiated new pharmacological treatment, 39.7% were lost to follow-up, and 11.8% opted not to start another treatment. The majority of patients that started a new pharmacology treatment switched to another anti-CGRP/R (46/68, 67.6%). The second most-used treatment was onabotulinumtoxinA (7/68, 10.2%; all patients in this subgroup were naïve to this treatment), followed by an anticonvulsive medication (7/68, 10.2%). The response status (≥50% reduction in monthly headache days) was achieved by 30.5%, 34.6%, and 40.0% of patients at month 3, 6, and 12 of treatment, respectively. Considering only the comprehensive last month of treatment before withdrawn the percentage of responders was 16.9%.

Conclusion: Although anti-CGRP/R mAbs have provided a substantial amelioration of migraine management, a relevant proportion of patients remains unresponsive and requires additional therapeutic support. Further research is required to identify non-responder features and address unmet needs in migraine treatment.

The migraine treatment landscape has seen significant advancements in recent years, including the introduction of novel preventive agents specifically targeting the disease. These new treatments offer improved efficacy and tolerability, potentially addressing the issue of poor treatment adherence commonly observed with conventional preventatives. In this context, pragmatic trials emerge as a critical tool for advancing migraine care, offering a real-world approach to evaluating open clinical questions at the same time as avoiding the biases of real-world observational evidence. By prioritizing external validity and patient-centered outcomes, pragmatic trials provide valuable insights into the advantages of new treatments in improving migraine care. Possible applications of pragmatic trials in migraine research include head-to-head comparisons, evaluation of combination therapies, assessment of treatment sequences and switch, testing the added value of patient-reported outcomes, investigation of long-term effectiveness and on optimal treatment duration, understanding the role of preventive treatments in altering the course of migraine and preventing progression, and cost-effectiveness analyses. Pragmatic trials allow for the assessment of interventions in diverse patient populations and healthcare settings, enhancing the generalizability of findings and informing evidence-based clinical practice. As such, pragmatic trials represent an excellent tool to bridge the gap between placebo-controlled trials and real-world practice and should receive consideration for funding, especially by public institutions such as universities, national health services, and charities.

Background: Time in headache disorders is crucial for diagnosis and gives insight into headache pathophysiology.

Objective: To summarize published studies which describe timing processes in both attack presentation (onset, duration) and disease characterization (age of onset, evolution over time) in primary headache disorders and link to pathophysiology.

Methods: A comprehensive search was conducted through Ovid MEDLINE(R) and PubMed, focusing on English-language articles from 1946 to 2023 to write the review. The International Classification of Headache Disorders, 3rd edition provided the framework for the review of primary headache disorders (migraine, tension-type headache and cluster headache).

Results: Attack presentation: Migraine attacks exhibit significant circadian and infradian rhythms, influenced by hormonal levels, light sensitivity, and hypothalamic activation. Tension-type headache lacks clear chronobiological patterns, with limited understanding of its underlying mechanisms. Cluster headache displays a distinct circannual pattern, with attacks often occurring at night and relevant involvement of the hypothalamus. Disease characterization: Age of onset exhibits the earliest peak in migraine; frequency and typical features of primary headache disorders decrease over time.

Conclusion: This comprehensive analysis of time patterns in primary headache disorders underscores their role in phenotyping, understanding and treating primary headache disorders, offering promising avenues for advancing and tailoring headache management.

Background: Medication overuse headache is a prevalent secondary headache due to the overuse of analgesics, mainly over-the-counter analgesics. Over-the-counter analgesics have been associated with disrupted male endocrinology, while the effects on female endocrinology remain nearly unknown. The aim was to understand the effect of long-term analgesic exposure in females with medication overuse headache on Anti-Müllerian hormone, a surrogate measure of female fertility.

Methods: Using a translational approach, an observational prospective clinical study was conducted to determine the effect of withdrawal therapy in females with medication overuse headache on Anti-Müllerian hormone levels, in combination with pre-clinical investigation of primary granulosa cells to understand the effects of analgesics on granulosa cell function.

Results: We included 21 females (mean-age 30.0 years; SD (7.3)) for Anti-Müllerian hormone -measurement. Anti-Müllerian Hormone increased by 21% from baseline (mean 20.1 pmol/L; SD (8.7)) after withdrawal of analgesics ((mean 24.3 pmol/L; SD (12.0)); p = 0.0023). Exposing primary granulosa cells to analgesics (acetaminophen (100 and 200 µM, n = 9-10) and ibuprofen (150 and 200 µM, n = 12-13)) did not reduce Anti-Müllerian hormone levels. In contrast, de novo DNA synthesis in GCs (n = 6) exposed to acetaminophen was reduced by 78% (p = 0.0036) compared to controls, suggesting that cellular proliferation was restricted.

Conclusion: We found that frequent use of over-the-counter analgesics was associated with repressed Anti-Müllerian Hormone levels, likely through disruption of granulosa cell proliferation. Further research is crucial to investigate a potential effect of analgesics on adult female reproductive endocrinology.Trial registration: ClinicalTrials.gov Identifier NCT04090333.