Search

Background: Menstrual migraine describes migraines that occur in alignment with the menstrual cycle, affecting women of diverse age ranges. This condition is relatively common, presenting a unique challenge due to the heightened intensity of pain during these attacks. Additionally, these migraines are often more resistant to standard treatment methods, underscoring the need for specialized approaches to management and relief. Methods: Review of double-blind, placebo-controlled cohort studies found using PubMed, Google Scholar and Cochrane. Results: Triptans are considered a primary treatment option for managing acute menstrual migraine episodes, with their effectiveness being the most extensively researched among available therapies. Recently, lasmiditan has emerged as a newer medication showing promising potential for this specific application as well, adding to the options available for menstrual migraine relief. Furthermore, triptans have been validated as effective in the short-term prevention of migraine. The most recent pharmacological advancements that have demonstrated efficacy for this condition are monoclonal antibodies which target the CGRP receptor: Erenumab and Galcanezumab. Conclusion: There are effective approaches to both treating and preventing acute migraine attacks. However, menstrual migraine is a condition that requires greater awareness and recognition, as this would allow for the improved and more effective use of existing medications and treatments. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). Methods: This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Results: Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2 years (± 11.9) at diagnosis and 40.6 (± 12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (± 4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. Conclusion: People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP) monoclonal antibodies in the treatment of episodic and chronic migraine was invetigated. A comprehensive literature search was conducted in Ovid Medline, Web of Science and Embase databases from their inception until April 2024 for randomized controlled trials comparing CGRP monoclonal antibodies with placebo or other active treatments in adults with episodic or chronic migraine. The primary outcome assessed was the incidence of hypertension, and secondary outcomes were tolerability, acceptability and adverse events. Data analysis was performed using a random-effects model, and the strength of evidence was evaluated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. A total of eleven studies involving 9729 participants were found eligible and included for data analysis. The results revealed that the pooled odds ratio for the incidence of hypertension in patients receiving CGRP monoclonal antibodies compared to placebo was (95% confidence interval (CI): 0.60, 2.21; I² = 32%), suggesting no significant increase in hypertension risk. Moreover, no significant differences were observed in tolerability or acceptability between the CGRP monoclonal antibody and placebo groups. However, the overall risk of total adverse events was significantly higher in the CGRP monoclonal antibody group (odds ratio (OR): 1.13; 95% CI: 0.97, 1.33; I² = 56%; p = 0.01). These findings indicate that CGRP monoclonal antibodies are well-tolerated and present a generally safe option for treating episodic and chronic migraine. Although there was no significant increase in the incidence of hypertension, a slight rise in overall adverse events was observed. Consequently, CGRP monoclonal antibodies may be considered a viable treatment option for patients who have not found other treatments effective or tolerable, or who have contraindications to alternative therapies. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk, registration number: CRD42024554897). [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) significantly impacts both the physical and mental health of patients. Current studies on the safety and effectiveness of different pharmacological prophylaxis interventions for CM are limited. To address this gap, we conducted a network meta-analysis (NMA) to compare and rank the efficacy and safety of various drugs in preventing CM. Methods: Two independent researchers systematically searched four databases from their inception to August 1, 2023, to identify eligible randomized controlled trials (RCTs). Subsequently, they performed data extraction and assessed the risk of bias. A NMA was then performed. Continuous outcomes and binary outcomes were displayed as weighted mean difference (WMD) and risk ratio (RR), respectively, and corresponding 95% confidence intervals (CI) were reported. The surface under the cumulative ranking curve (SUCRA) was used to rank each intervention separately. Results: 24 RCTs involving 8789 patients were included. Compared to placebo, Botulinum toxin A demonstrated the most significant effect in reducing the monthly migraine days for CM patients (MD = 3.88, 95% CI 0.48, 7.28); in terms of improving the response rate by a 50% reduction in monthly migraine days, Topiramate (RR = 50.06, 95% CI 3.18, 787.30) was the most effective; there was no statistically significant difference between all preventive drugs and placebo in improving the migraine disability assessment (MIDAS) score; in terms of the incidence of adverse events, Eptinezumab (RR = 1.09, 95% CI 0.8, 1.54) exhibited the highest safety profile. Conclusion: Among all the drugs for the preventive drugs for CM, Botulinum toxin A has the best efficacy and safety profile, closely followed by calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP-mAbs) are approved for adult migraine prevention but pose safety concerns in pregnancy. We assess the safety of CGRP-mAbs in the periconceptional period through a case series and literature review. Methods: Six migraine-diagnosed women received CGRP-mAbs; treatment ceased upon pregnancy. We collected data and conducted safety assessments. To provide a comprehensive context, we performed a literature review. Results: The series includes three erenumab, two fremanezumab and one galcanezumab case. A fremanezumab recipient experienced miscarriage; severe perinatal asphyxia linked to dystocia occurred with erenumab (140 mg). Database reviews revealed 63 spontaneous abortions, eight premature births, and seven birth defects among 286 World Health Organization and 65 European Medicines Agency cases. These rates align with untreated population rates. Conclusions: CGRP-mAbs use in the periconceptional period does not lead to clinically significant increase in pregnancy-related pathology or adverse effects on newborns within our case series and the literature reviewed. [ABSTRACT FROM AUTHOR]

Background Menstrual migraine describes migraines that occur in alignment with the menstrual cycle, affecting women of diverse age ranges. This condition is relatively common, presenting a unique challenge due to the heightened intensity of pain during these attacks. Additionally, these migraines are often more resistant to standard treatment methods, underscoring the need for specialized approaches to management and relief. Methods Review of double-blind, placebo-controlled cohort studies found using PubMed, Google Scholar and Cochrane. Results Triptans are considered a primary treatment option for managing acute menstrual migraine episodes, with their effectiveness being the most extensively researched among available therapies. Recently, lasmiditan has emerged as a newer medication showing promising potential for this specific application as well, adding to the options available for menstrual migraine relief. Furthermore, triptans have been validated as effective in the short-term prevention of migraine. The most recent pharmacological advancements that have demonstrated efficacy for this condition are monoclonal antibodies which target the CGRP receptor: Erenumab and Galcanezumab. Conclusion There are effective approaches to both treating and preventing acute migraine attacks. However, menstrual migraine is a condition that requires greater awareness and recognition, as this would allow for the improved and more effective use of existing medications and treatments.

Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) have shown promising effectiveness in migraine management compared to other preventative treatment options. Many questions remain regarding switching between antibody classes as a treatment option in patients with migraine headaches. This preliminary retrospective real-world study explored the treatment response of patients who switched between CGRP mAb classes due to lack of efficacy or poor tolerability. A total of 53 patients with migraine headache switched between three of the CGRP mAbs types due to lack of efficacy of the original prescribed CGRP mAbs, specifically eptinezumab, erenumab, and galcanezumab. Fremanezumab was not included due to unavailability in the UAE. Galcanezumab and eptinezumab target the CGRP ligand (CGRP/L), while erenumab targets CGRP receptors (CGRP/R). The analysis of efficacy demonstrated that some improvements were seen in both class switch cohorts (CGRP/R to CGRP/L and CGRP/L to CGRP/R). The safety of switching between CGRP classes was well observed, as any adverse events presented before the class switch did not lead to the discontinuation of treatment following the later switch. The findings of this study suggest that switching between different classes of CGRP mAbs is a potentially safe and clinically viable practice that may have some applications for those experiencing side effects on their current CGRP mAb or those witnessing suboptimal response.

Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) have shown promising effectiveness in migraine management compared to other preventative treatment options. Many questions remain regarding switching between antibody classes as a treatment option in patients with migraine headaches. This preliminary retrospective real-world study explored the treatment response of patients who switched between CGRP mAb classes due to lack of efficacy or poor tolerability. A total of 53 patients with migraine headache switched between three of the CGRP mAbs types due to lack of efficacy of the original prescribed CGRP mAbs, specifically eptinezumab, erenumab, and galcanezumab. Fremanezumab was not included due to unavailability in the UAE. Galcanezumab and eptinezumab target the CGRP ligand (CGRP/L), while erenumab targets CGRP receptors (CGRP/R). The analysis of efficacy demonstrated that some improvements were seen in both class switch cohorts (CGRP/R to CGRP/L and CGRP/L to CGRP/R). The safety of switching between CGRP classes was well observed, as any adverse events presented before the class switch did not lead to the discontinuation of treatment following the later switch. The findings of this study suggest that switching between different classes of CGRP mAbs is a potentially safe and clinically viable practice that may have some applications for those experiencing side effects on their current CGRP mAb or those witnessing suboptimal response. [ABSTRACT FROM AUTHOR]

BackgroundMonoclonal antibodies to calcitonin gene-related peptide or its receptor have clinical trial evidence in adults with headache, but data are lacking in adolescents. The objective of this study was to describe the safety and efficacy of calcitonin gene-related peptide monoclonal antibody treatment in adolescents with chronic headache disorders.MethodsWe performed a retrospective multisite cohort study of patients less than 18 years of age who received a calcitonin gene-related peptide monoclonal antibody for headache prevention. Demographics, baseline headache characteristics, efficacy, and side effect data were collected.ResultsThe study population comprised 112 adolescents who received at least one dose of a calcitonin gene-related peptide monoclonal antibody. Mean (S.D.; range) age at first dose was 15.9 years (1.4; 10.3 to 17.8). Ninety-four patients (83.9%) had chronic migraine, 12 (10.7%) had new daily persistent headache, and six (5.4%) had persistent post-traumatic headache. At baseline, the mean (S.D.) number of headache days per month was 26.9 (6.1) (n = 109) and headache was continuous in 75 of 111 (67.6%). At first follow-up visit there was a significant reduction in headache frequency compared with baseline (-2.0 days; 95% confidence interval, -0.8 to -3.2). Significant benefit was perceived by 29.5% of patients at first follow-up visit (n = 33/112) and 30.1% (n = 22/73) at second follow-up visit. A significant functional improvement was perceived by 31% of patients (n = 31/94) at the first follow-up visit and 22.4% (n = 15/67) at the second follow-up visit. The most common side effects were injection site reactions in 17.0% (n = 19) and constipation in 8.0% (n = 9). Five patients (4.5%) discontinued because of side effects.ConclusionsSide effects with calcitonin gene-related peptide monoclonal antibody treatment in adolescents were similar to those reported in adult trials. Calcitonin gene-related peptide monoclonal antibody treatment appears to benefit a proportion of adolescents with chronic refractory headache disorders.

Abstract Objective While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. Methods We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. Results We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. Conclusions (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.

Abstract Background The goal of this observational, open-label, cohort study was to determine whether prophylactic migraine treatment with galcanezumab, a peripherally acting drug, alters the incidence of premonitory symptoms, and/or occurrence of headache after exposure to triggers or aura episodes in treatment-responders (≥ 50% reduction in monthly migraine days [MMD]), super-responders (≥ 70%), non-responders (

Objective: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. Methods: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. Results: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. Conclusions: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants. [ABSTRACT FROM AUTHOR]

Background: A new migraine prevention, CGRP monoclonal antibodies (mAbs), is injectable on a monthly or quarterly basis. In clinical practice, some patients reported that drug effectiveness does not last until the upcoming scheduled injection, a so-called "wearing-off" effect. We aimed to evaluate the wearing-off effect of the CGRP mAbs for migraine prevention in patients with different monthly migraine days. Methods: We conducted a literature search for studies that reported migraine frequency after CGRP monoclonal antibody administration from MEDLINE, SCOPUS, Web of Science, and Cochrane Database from inception through February 2022. A meta-analysis, random-effects model was applied to assess the difference in migraine frequency between early and later weeks after medication to assess the presence of a wearing-off effect. Risk ratio was calculated to report the pooled treatment effect. Results: Four studies were entered for the analysis, comprising 2409 patients in randomized controlled trials. There was no association between CGRP mAbs and wearing-off effect in patients with galcanezumab with a pooled risk ratio of 1.29 (95% CI 0.73 to 2.28) compared to placebo group. However, there was an association between galcanezumab and wearing-off effect in patients with chronic migraine with a pooled risk ratio of 1.91 (95% CI 1.11 to 3.28) compared to placebo group. Conclusion: In this meta-analysis, there was a wearing-off efficacy of galcanezumab but only in a small percentage of patients with chronic migraine in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. Methods We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed. Results Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (€17,720) and £16,598 (€19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (€218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips’s checklist for economic models. Conclusions Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.

Background: The goal of this observational, open-label, cohort study was to determine whether prophylactic migraine treatment with galcanezumab, a peripherally acting drug, alters the incidence of premonitory symptoms, and/or occurrence of headache after exposure to triggers or aura episodes in treatment-responders (≥ 50% reduction in monthly migraine days [MMD]), super-responders (≥ 70%), non-responders (< 50%) and super non-responders (< 30%). Methods: Participants were administered electronic daily headache diaries to document migraine days and associated symptoms one month before and during the three months of treatment. Questionnaires were used to identify conscious prodromal and trigger events that were followed by headache prior to vs. after 3 months of treatment. Results: After 3 months of galcanezumab treatment, (a) the incidence of premonitory symptoms that were followed by headache decreased by 48% in the 27 responders vs. 28% in the 19 non-responders, and by 50% in the 11 super-responders vs. 12% in the 8 super non-responders; (b) the incidence of visual and sensory aura that were followed by headache was reduced in responders, non-responders, and super-responders, but not in super non-responders; (c) the number of triggers followed by headache decreased by 38% in responders vs. 13% in non-responders, and by 31% in super-responders vs. 4% in super non-responders; and (d) some premonitory symptoms (e.g., cognitive impairment, irritability, fatigue) and triggers (e.g., stress, sleeping too little, bright light, aura) were followed by headache only in super non-responders. Conclusions: Mechanistically, these findings suggest that even a mild decrease in migraine frequency is sufficient to partially reverse the excitability and responsivity of neurons involved in the generation of certain triggers and potentially premonitory symptoms of migraine. Trial registration: ClinicalTrials.gov: NCT04271202. Registration date: February 10, 2020. [ABSTRACT FROM AUTHOR]

Background: Migraine is a complex neurological disorder involving generalized abnormalities in processing sensory information. Adopting evidence that central sensitization imposes major hurdles in the treatment of migraine, we hypothesized that it is the non-ictal (rather than ictal) allodynia that may determine the outcome of migraine prevention with peripherally-acting drugs. Methods: To test this hypothesis, we used Quantitative Sensory Testing to determine whether it is possible to identify a patient's response to prophylactic treatment with galcanezumab based on presence/absence of cephalic and/or extracephalic allodynia during the pre-treatment non-ictal phase of migraine. Results: Using strict criteria for allodynia (heat 32-40°C, cold 32-20°C, mechanical <60 g), we report that (a) the incidence of pre-treatment non-ictal cephalic allodynia was 21% in the 24 responders (>50% decrease in monthly migraine days) and 85% in the 19 non-responders; (b) the incidence of non-ictal extracephalic allodynia distinguishes responders from non-responders less accurately; and that (c) the incidence of non-ictal cephalic allodynia was similar in the chronic migraine and high-frequency episodic migraine groups. Conclusions: Clinically, the findings suggest that presence/absence of non-ictal allodynia can be used to identify galcanezumab responders with nearly 80% accuracy and galcanezumab non-responders with nearly 85% accuracy. Mechanistically, the presence of non-ictal allodynia (reflecting a state of activity-independent central sensitization) in both chronic migraine and high-frequency episodic migraine patients raises the possibility that the state of non-ictal allodynia may be attributed to physiological properties of central trigeminovascular neurons that are due to the genetic load of the individual patient rather than their migraine frequency. [ABSTRACT FROM AUTHOR]

The diagnosis of chronic migraine (CM) is made when there are 15 or more days of headache per month in a patient with migraine. Approximately 2.5% of patients with episodic migraine develop chronic migraine, which is more difficult to treat and often leads to drug-induced headache (LIH). Such patients are rarely included in clinical trials. Aim. To analyze in clinical practice the effectiveness of the CGRP monoclonal antibody erenumab after 6 months of therapy in patients with CM with and without LIHD, and to evaluate possible predictors of the effectiveness of prophylactic therapy. Materials and methods. The study included 47 patients with CM taking erenumab at a dose of 70 mg monthly for at least 3 months. Patients completed a headache diary throughout the study. The 12-item Allodynia Symptom Checklist (ACS-12) was used to assess the presence of allodynia. After 6 months of therapy, the efficacy and safety of treatment, the presence of LAH and possible predictors of efficacy were evaluated. Results. After 6 months of therapy, 22 (78.6%) patients no longer met the criteria for LIHD. The factors that positively influenced the outcome of therapy were the absence of allodynia (p0.05), the presence of photo- and phonophobia, and the one-sidedness of pain (p0.05). The age and number of days with headache in patients with HM before treatment did not have a statistically significant effect on the effect of therapy. The presence of LIHD did not statistically significantly affect the outcome of therapy. Conclusion. CGRP monoclonal antibodies are reasonable in patients with LIHD. The presence of LIHD does not affect the efficacy of erenumab prophylactic therapy, the presence of allodynia may be a predictor of failure, and the unilaterality of pain and irritability to light and sound indicate likely efficacy. Real-world studies with a large cohort of patients and longer durations of therapy are required to confirm these results.

The discovery of calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology has led to advances in the treatment of migraine. Since 2018, the Food and Drug Administration (FDA) has approved four monoclonal antibody (mab) therapies targeting either the CGRP ligand or receptor and 3 oral small molecule CGRP receptor antagonists. These targeted therapies have been shown to be safe and effective for either preventive or acute treatment of migraine in adults. Given their efficacy and tolerability profile, CGRP inhibitors have revolutionized the approach to migraine treatment. Theoretically, combining therapies within this therapeutic class could lead to more CGRP blockade and, subsequently, improved patient outcomes. There are providers currently combining CGRP therapies in clinical practice. However, limited data are available regarding the efficacy and safety of this practice. This mini-review provides a summary of available data and poses important considerations when combining CGRP therapies for migraine treatment.

Background and aims: Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. Methods: We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed. Results: Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (€17,720) and £16,598 (€19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (€218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips's checklist for economic models. Conclusions: Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies. [ABSTRACT FROM AUTHOR]

Background: This study investigated the mechanism of action of atogepant, a small-molecule CGRP receptor antagonist recently approved for the preventive treatment of episodic migraine, by assessing its effect on activation of mechanosensitive C- and Aδ-meningeal nociceptors following cortical spreading depression. Methods: Single-unit recordings of trigeminal ganglion neurons (32 Aδ and 20 C-fibers) innervating the dura was used to document effects of orally administered atogepant (5 mg/kg) or vehicle on cortical spreading depression-induced activation in anesthetized male rats. Results: Bayesian analysis of time effects found that atogepant did not completely prevent the activation of nociceptors at the tested dose, but it significantly reduced response amplitude and probability of response in both the C- and the Aδ-fibers at different time intervals following cortical spreading depression induction. For C-fibers, the reduction in responses was significant in the early phase (first hour), but not delayed phase of activation, whereas in Aδ-fibers, significant reduction in activation was apparent in the delayed phase (second and third hours) but not early phase of activation. Conclusions: These findings identify differences between the actions of atogepant, a small molecule CGRP antagonist (partially inhibiting both Aδ and C-fibers) and those found previously for fremanezumab, a CGRP-targeted antibody (inhibiting Aδ fibers only) and onabotulinumtoxinA (inhibiting C-fibers only)- suggesting that these agents differ in their mechanisms for the preventive treatment of migraine. [ABSTRACT FROM AUTHOR]

Migraine is a common malady cutting across socioeconomic and ethnic divides in Australia. It is typically diagnosed late with significant impact on quality of life. Management options have emerged over the past several years that promise simpler treatment regimens with less potential for side‐effects. The development of rationally designed migraine preventives is the most significant advance in treatment since the development of the triptans and delivers significant hope to many headache sufferers. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP) monoclonal antibodies in the treatment of episodic and chronic migraine was invetigated. A comprehensive literature search was conducted in Ovid Medline, Web of Science and Embase databases from their inception until April 2024 for randomized controlled trials comparing CGRP monoclonal antibodies with placebo or other active treatments in adults with episodic or chronic migraine. The primary outcome assessed was the incidence of hypertension, and secondary outcomes were tolerability, acceptability and adverse events. Data analysis was performed using a random-effects model, and the strength of evidence was evaluated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. A total of eleven studies involving 9729 participants were found eligible and included for data analysis. The results revealed that the pooled odds ratio for the incidence of hypertension in patients receiving CGRP monoclonal antibodies compared to placebo was (95% confidence interval (CI): 0.60, 2.21; I 2 = 32%), suggesting no significant increase in hypertension risk. Moreover, no significant differences were observed in tolerability or acceptability between the CGRP monoclonal antibody and placebo groups. However, the overall risk of total adverse events was significantly higher in the CGRP monoclonal antibody group (odds ratio (OR): 1.13; 95% CI: 0.97, 1.33; I = 0.01). These findings indicate that CGRP monoclonal antibodies are well-tolerated and present a generally safe option for treating episodic and chronic migraine. Although there was no significant increase in the incidence of hypertension, a slight rise in overall adverse events was observed. Consequently, CGRP monoclonal antibodies may be considered a viable treatment option for patients who have not found other treatments effective or tolerable, or who have contraindications to alternative therapies. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk, registration number: CRD42024554897).2 = 56%; p = 0.01). These findings indicate that CGRP monoclonal antibodies are well-tolerated and present a generally safe option for treating episodic and chronic migraine. Although there was no significant increase in the incidence of hypertension, a slight rise in overall adverse events was observed. Consequently, CGRP monoclonal antibodies may be considered a viable treatment option for patients who have not found other treatments effective or tolerable, or who have contraindications to alternative therapies. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk, registration number: CRD42024554897)., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Background: One of the advantages of CGRP monoclonal antibodies is their excellent safety and tolerability. However, postmarketing surveillance, is essential to detect potential rare emergent adverse events. Objectives: To report two patients who developed restless legs syndrome symptoms after treatment with CGRP antibodies. Methods and results: Two women with chronic refractory migraine, with no significant medical antecedents, developed typical restless legs syndrome symptoms 1.5 and 4 months after starting erenumab 140 mg, respectively. In case 1 symptoms resolved when erenumab was stopped for two months but reappeared on galcanezumab. In both patients migraine attacks had dramatically decreased and no iron deficiency was found. Conclusions: Even though caution is needed before establishing a causal relationship, these cases suggest that restless legs-like symptoms might be an emergent adverse event of CGRP antibodies, regardless of the mechanism of action. We propose that plastic changes in CGRP sensory fibers, which are very abundant in legs, induced by CGRP monoclonal antibodies could be the reason for restless legs syndrome development. [ABSTRACT FROM AUTHOR]

Abstract Raynaud's phenomenon is a rare side effect of CGRP monoclonal antibodies. These molecular treatments are a relatively new class of drugs for the prevention of migraine. It is likely that we will see this side effect more often in the future. Patients with a background of Raynaud's phenomenon may experience worsening of their symptoms if started on these treatments.

Raynaud's phenomenon is a rare side effect of CGRP monoclonal antibodies. These molecular treatments are a relatively new class of drugs for the prevention of migraine. It is likely that we will see this side effect more often in the future. Patients with a background of Raynaud's phenomenon may experience worsening of their symptoms if started on these treatments. [ABSTRACT FROM AUTHOR]

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis.Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score.Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate.Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Background: Monoclonal antibodies to calcitonin gene-related peptide or its receptor have clinical trial evidence in adults with headache, but data are lacking in adolescents. The objective of this study was to describe the safety and efficacy of calcitonin gene-related peptide monoclonal antibody treatment in adolescents with chronic headache disorders.Methods: We performed a retrospective multisite cohort study of patients less than 18 years of age who received a calcitonin gene-related peptide monoclonal antibody for headache prevention. Demographics, baseline headache characteristics, efficacy, and side effect data were collected.Results: The study population comprised 112 adolescents who received at least one dose of a calcitonin gene-related peptide monoclonal antibody. Mean (S.D.; range) age at first dose was 15.9 years (1.4; 10.3 to 17.8). Ninety-four patients (83.9%) had chronic migraine, 12 (10.7%) had new daily persistent headache, and six (5.4%) had persistent post-traumatic headache. At baseline, the mean (S.D.) number of headache days per month was 26.9 (6.1) (n = 109) and headache was continuous in 75 of 111 (67.6%). At first follow-up visit there was a significant reduction in headache frequency compared with baseline (-2.0 days; 95% confidence interval, -0.8 to -3.2). Significant benefit was perceived by 29.5% of patients at first follow-up visit (n = 33/112) and 30.1% (n = 22/73) at second follow-up visit. A significant functional improvement was perceived by 31% of patients (n = 31/94) at the first follow-up visit and 22.4% (n = 15/67) at the second follow-up visit. The most common side effects were injection site reactions in 17.0% (n = 19) and constipation in 8.0% (n = 9). Five patients (4.5%) discontinued because of side effects.Conclusions: Side effects with calcitonin gene-related peptide monoclonal antibody treatment in adolescents were similar to those reported in adult trials. Calcitonin gene-related peptide monoclonal antibody treatment appears to benefit a proportion of adolescents with chronic refractory headache disorders. [ABSTRACT FROM AUTHOR]

Background: Migraines are a common comorbidity and source of disability in patients with chronic inflammatory diseases like multiple sclerosis (MS). Recently, therapeutic agents for episodic and chronic migraine known as calcitonin gene-related peptide (CGRP) inhibitors have shown to effectively control migraine attacks and improve quality of life in the general population. This study explored the use of these novel agents in individuals with comorbid MS., Methods: This was a retrospective, population-based cohort study at the University of South Florida's neurology clinic; it evaluated individuals with both MS and migraine., Results: A total of 27 individuals with MS and chronic or episodic migraine who received treatment with a CGRP monoclonal antibody were identified. Of these, 63% reported a reduction in their migraine frequency of greater than 75%. Concurrent use of a disease-modifying therapy (DMT) for MS occurred in 82% of patients, and in 37% of these, the DMT used was also a monoclonal antibody. Adverse effects from CGRP monoclonal antibodies were mild and occurred in only 11% of patients, and no patient experienced worsening of their MS symptoms during cotreatment over the duration of the study., Conclusions: Our study showed a significant reduction in migraine frequency and a favorable adverse event profile for individuals with comorbid MS who took CGRP monoclonal antibodies and experienced no worsening of MS symptoms. In individuals with MS, CGRP monoclonal antibodies seem to be a safe and effective therapy for episodic or chronic migraine., Competing Interests: PRIOR PRESENTATION: This data was previously presented at the 2022 Consortium of Multiple Sclerosis Centers Annual Meeting; June 2, 2022; National Harbor, Maryland., (© 2024 Consortium of Multiple Sclerosis Centers.)

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Migraine is the most disabling and expensive chronic disorders, the etiology of which is still not fully known. The neuronal systems, (glutammatergic, dopaminergic, serotoninergic and GABA-ergic) whose functionality is partly attributable to genetically determined factors, has been suggested to play an important role. The treatment of acute attacks and the prophylactic management of chronic forms include the use of different category of drugs, and it is demonstrated that not each subject has the same clinical answer to them. The reason of this is to be searched in different functional capacity and quantity of phase I enzymes (such as different isoforms of CYP P450), phase II enzymes (such as UDP-glucuronosyltransferases), receptors (such as OPRM1 for opioids) and transporters (such as ABCB1) involved in the metabolic destiny of each drug, all of these dictated by DNA and RNA variations. The general picture is further exacerbated by the need for polytherapies, often also to treat comorbidities, which may interfere with the pharmacological action of anti-migraine drugs. Personalized medicine has the objective of setting the optimal therapies in the light of the functional biochemical asset and of the comorbidities of the individual patient, in order to obtain the best clinical response. Novel therapeutic perspectives in migraine includes biotechnological drugs directed against molecules (such as CGRP and its receptor) that cause vasodilatation at the peripheral level of the meningeal blood vessels and reflex stimulation of the parasympathetic system. Drug-drug interactions and the possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. Drug-drug interactions and their possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. [ABSTRACT FROM AUTHOR]

The evidence base for migraine prevention in both episodic and chronic migraine is outlined. The older oral preventatives, including antidepressants, antihypertensives, serotonin antagonists, antiepileptics, and calcium channel antagonists, and newer options including onabotulinumtoxinA and the CGRP monoclonal antibodies are covered. Many of the older oral preventatives were trialed before chronic migraine was defined, and they are used in chronic migraine based on the assumption that episodic migraine and chronic migraine are on a spectrum of the same condition. First- and second-line options are given, and a multicountry perspective is considered., (Copyright © 2024 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Though clearly described as far back as the 17th century, chronic migraine has defied precise categorization and has continued to develop as an important diagnostic concept with significant societal impact. Worldwide prevalence is estimated to be between 1% and 3%, and these patients form a dynamic group cycling between chronic and episodic migraine. Theories of pathogenesis are developing supported by recent imaging and other findings. Of the many determinants of progression to chronic migraine, overuse of acute abortive headache medications may be one of the most important modifiable factors. Treatment strategies, in addition to educational measures, have included various preventive migraine medications such as topiramate, valproate, and onabotulinumtoxinA. CGRP monoclonal antibodies are efficacious for the management of chronic migraine both with and without medication overuse., (Copyright © 2023 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted. [ABSTRACT FROM AUTHOR]

Episodic migraine is a debilitating condition. Preventive therapy is used to reduce frequency, duration, or severity of attacks. This review discusses principles of preventive treatment with a focus on preventive treatment options for people with episodic migraine. Specifically discussed is evidence and use of new migraine-specific treatment options for episodic migraine, such as calcitonin gene-related peptide monoclonal antibodies, a noninvasive transcutaneous electrical nerve stimulation device, and a single-pulse transcranial magnetic stimulator device. Also discussed are evidence-based updates from the 2012 American Academy of Neurology and the American Headache Society guidelines regarding major medication classes recommended for preventive episodic migraine treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Migraine is among the commonest causes of headache in all ages. It is the second most common cause of neurological disability. Currently, antihypertensive, antidepressants and antiepileptic drugs are reasonable preventable medications for chronic migraine. Despite the higher levels of stigma associated with this disease, fewer attempts were made in past regarding the treatment options for chronic migraine. Recently, a novelty treatment was introduced known as calcitonin gene-related peptide (CGRP) monoclonal antibodies as a possible mechanism for the prevention of migraine attacks. CGRP played an important role in the etiology of migraine headaches and was considered as the major peptide behind the cause of the headache disorders. We have reviewed the benefits of these monoclonal antibodies in terms of their efficacy and adverse effects with the available treatment choices. These drugs showed superior results when compared to the placebo and were considered generally safe in the majority of clinical trials. Earlier versions of CGRP antagonists, known as gepants, were less tolerable due to their tendency to cause liver and cardiovascular complications. Thus, in comparison to the earlier gepants, these CGRP monoclonal antibodies were safer and demonstrated excellent tolerability. Short-term side effects were only limited to mild-moderate injection site rash or pruritus, however, their long-term side effects are still unknown. Despite the higher cost of these drugs, we have analyzed the applicability of this drug in the developing countries. Although the quality-adjusted life year (QALY) gained per cost of the drug is still expensive and majority of people may not afford, its excellent tolerability and less adverse effects should also be considered a reason to implement this drug, particularly for resource-limited countries. Moreover, these medications could also become a prototype for future inventions and creations (cost-effective versions for resource-limited countries). In conclusion, this review suggests that CGRP monoclonal antibodies are safer and excellent alternate option for patients with chronic migraine as it has better efficacy, tolerability, and provides a hope to reduce the stigma associated with migraine. All these benefits should be the deciding factors when opting for this treatment and the decision should not be made solely on the socioeconomic status., Competing Interests: The authors have declared that no competing interests exist.