Calcitonin Gene-related Peptide mAbs Research Articles

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Long-Term Outcome After Discontinuation of CGRP-Targeting Therapy for Migraine.

Calcitonin gene-related peptide (CGRP)-targeting agents are potential candidates for disease-modifying migraine drugs. However, most studies on CGRP-targeting agents have assessed efficacy outcomes rather than long-term effects after discontinuation. This review aimed to synthesize and scrutinize the latest clinical data on the outcomes after the discontinuation of CGRP-targeting therapy in patients with episodic and chronic migraine, with a particular focus on chronic migraine. Real-world studies involving patients with migraine have reported consistent findings of worsened headache frequency and quality of life after the discontinuation of CGRP monoclonal antibodies (CGRP mAbs). Although many patients maintain improvements for up to 4months after discontinuation compared to baseline (before starting CGRP mAbs), no studies have evaluated the effects of stopping treatment for > 5months, which is the five-half-life of CGRP mAbs. Several studies have suggested that patients treated with CGRP receptor mAbs experience more rapid deterioration than those treated with CGRP ligand mAbs after discontinuing CGRP mAbs. The results of real-world studies suggest that for many patients with migraine, the benefits of CGRP mAbs diminish months after discontinuation. Therefore, anti-CGRP therapies may not be considered disease-modifying. However, the comprehensive assessment of the disease-modifying potential of these drugs requires studies with extended treatment and cessation durations.

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

BackgroundMigraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that...

Update on gepants for the treatment of chronic migraine.

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.

Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers

BackgroundAlthough randomized controlled trials (RCTs) have shown that calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (CGRP mAbs) are an efficacious and safe therapeutic modality for migraine prevention, their clinical benefits have not been well validated in Japanese patients in the real-world setting. The present study aimed to evaluate the real-world efficacy and safety of galcanezumab, fremanezumab, and erenumab in Japanese patients with migraine.MethodsThis observational retrospective cohort study was conducted at two headache centers in Japan. Patients with migraine who had experienced treatment failure with at least one traditional oral migraine preventive agent were treated with a CGRP mAb de novo. The primary efficacy endpoints were the changes from baseline in monthly migraine days (MMDs) and Headache Impact Test-6 (HIT-6) score after 3 dosing intervals (V3). We explored whether demographic and clinical characteristics predicted therapeutic outcomes at V3.ResultsSixty-eight patients who completed three doses of a CGRP mAb (85.3% female [58/68], mean age: 46.2 ± 13.1 years) were included in the analysis. There were 19 patients with chronic migraine. The baseline MMDs were 13.4 ± 6.0. After 3 doses, the MMDs significantly decreased to 7.4 ± 5.5 (p < 0.0001), and the 50% response rate was 50.0%. HIT-6 score was significantly reduced from 66.7 ± 5.4 to 56.2 ± 8.7 after 3 doses (P = 0.0001). There was a positive correlation between the changes in MMDs and HIT-6 score from baseline after 2 doses (p = 0.0189). Those who achieved a ≥ 50% therapeutic response after the first and second doses were significantly more likely to do so at V3 (crude odds ratio: 3.474 [95% CI: 1.037 to 10.4], p = 0.0467). The most frequent adverse event was constipation (7.4%). None of the adverse events were serious, and there was no need for treatment discontinuation.ConclusionsThis real-world study demonstrated that CGRP mAbs conferred Japanese patients with efficacious and safe migraine prevention, and an initial positive therapeutic response was predictive of subsequent favorable outcomes. Concomitant measurement of MMDs and HIT-6 score was useful in evaluating the efficacy of CGRP mAbs in migraine prevention.

An exploratory comparative case series of calcitonin gene-related peptide monoclonal antibodies in patients with migraine with rosacea.

Rosacea is associated with &amp;gt; 50% of cases of migraine. Recent data have shown that calcitonin gene-related peptide (CGRP) is elevated in rosacea skin. CGRP monoclonal antibodies (mAbs) prevent migraine with known safety profiles, but their effect on rosacea is not known. This exploratory retrospective study examined rosacea in patients with migraines, before and after CGRP mAbs. Of 13 eligible patients on stable or unchanged concurrent rosacea medications, the majority experienced improvement after receiving CGRP mAbs. Mean (SD) rosacea severity scores for the periods before and while on CGRP mAbs were, respectively, 1.19 (0.65) and 0.58 (0.70) (P = 0.01). Prospective, placebo-controlled clinical trials are needed to further assess the use of CGRP mAbs in rosacea.

Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Calcitonin gene-related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19. To evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death. This retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022. Initiation of CGRP mAbs. The main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes. Among 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability-weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2. In this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.

Treatment of hemiplegic migraine with anti‐calcitonin gene‐related peptide monoclonal antibodies: A case series in a tertiary‐care headache center

AbstractHemiplegic migraine (HM) is a subtype of migraine with aura that includes motor weakness; such headaches can be excruciating. The presence of not only headache but also aura symptoms of HM increase the burden on patients, and the treatment of HM is sometimes challenging. Monoclonal antibodies (mAbs) targeting the calcitonin gene‐related peptide (CGRP) pathway are novel migraine preventive treatments that have shown promising efficacy in patients with migraine; however, there have been no reports regarding their efficacy in HM to date. Six patients with HM were treated with galcanezumab in a tertiary‐care headache center. After 3 months of treatment, the number of monthly days with headache of at least moderate severity was reduced in three patients. The number of days each month with weakness was also reduced in four patients. Furthermore, the Patient's Global Impression of Change and change in Migraine Disability Assessment total score, were improved in five of the six patients after the treatment; however, the change from baseline in days with bothersome symptoms did not show any specific trends in our patients. Notably, no adverse events were reported during the treatments. The mechanism underlying the improvement in aura symptoms in our patients is not clear; however, we speculate that a small amount of CGRP mAbs have a direct mode of action in the central nervous system; alternatively, blocking the CGRP pathway in the periphery may secondarily inhibit cortical spreading depression. While prudence must be practiced, galcanezumab was still generally effective in HM and well tolerated. Further prospective clinical studies will more clearly elucidate the effects of CGRP mAbs in patients with HM.

Adherence and Persistence among Patients with Migraine Initiating Concomitant Use of Self-Injectable Calcitonin Gene-related Peptide Monoclonal Antibody and Novel Acute Migraine Medications (P10-12.007)

<h3>Objective:</h3> To describe demographics, clinical characteristics, and treatment patterns (adherence and persistence) among patients with migraine who concomitantly initiated self-injectable CGRP mAbs and novel acute migraine medications. <h3>Background:</h3> Limited evidence is available on real-world treatment patterns of patients initiating concomitant use of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and novel acute migraine medications. <h3>Design/Methods:</h3> This retrospective observational study utilized de-identified patient claims data from Merative MarketScan® Research Databases. Included patients initiated self-injectable CGRP mAbs (galcanezumab/erenumab/fremanezumab) and novel acute migraine medications (lasmiditan/rimegepant/ubrogepant) between May 2018 and February 2021, with an overlap between the two. Overlap was defined as ≥2 fills of the index drug (CGRP mAb or novel acute medication, whichever started first), 2 fills of the second drug (novel acute medication if CGRP mAb was the index drug or vice versa), or ≥1 fill each of the index and second drugs within 3 months of index drug initiation. Index date was the date of CGRP mAb initiation. Adherence to CGRP mAbs was assessed as proportion of days covered (PDC) and medication possession ratio (MPR) over a 12-month post-index period. Persistence was defined as the number of days of continuous preventive therapy from index until the end of post-index period, allowing for a maximum gap between fills of 60 days. <h3>Results:</h3> Of the 4,167 patients identified (mean [SD] age: 43.7 [11.2] years; 89.2% females), 59.7% had chronic migraine and 85.0% had CGRP mAbs as their index drug. Anxiety was the most common comorbidity (41.3%). Mean (SD) PDC was 0.7 (0.3) and 47.1% of patients achieved PDC≥0.8. Mean (SD) MPR was 0.9 (0.1) and 80.1% patients achieved MPR≥0.8. Mean (SD) days of persistence for index drug was 273.4 (115.3). <h3>Conclusions:</h3> Understanding treatment patterns among patients initiating concomitant use of CGRP mAbs and novel acute medications may provide valuable insight to providers when evaluating migraine treatment regimens. <b>Disclosure:</b> Miss Varnado has received personal compensation for serving as an employee of Eli Lilly and Company. Miss Varnado has stock in Eli Lilly and Company. Ms. Gulati has nothing to disclose. Dr. Hoyt has received personal compensation for serving as an employee of Eli Lilly and Co.. Dr. Hoyt has stock in Eli Lilly and Co.. Dr. Wheeler has received personal compensation for serving as an employee of Eli Lilly. Dr. Wheeler has stock in Eli Lilly. Jerry Hall has received personal compensation for serving as an employee of Eli Lilly &amp; Co.. Jerry Hall has stock in Eli Lilly &amp; Co..

Persistence to OnabotulinumtoxinA or Calcitonin Gene-Related Peptide Monoclonal Antibody Therapy Among Patients With Migraine: A Retrospective Cohort Study (P10-12.001)

<h3>Objective:</h3> To compare treatment persistency among patients with migraine on calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs; erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA. <h3>Background:</h3> To date, real-world evidence on persistence to CGRP mAbs or onabotulinumtoxinA have excluded eptinezumab. <h3>Design/Methods:</h3> This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with a CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A “most recent treatment episode” analysis was used in which the most recent episode was defined as the latest treatment period with the same drug (CGRP mAb or onabotulinumtoxinA) without a 15-day gap in medication supply on/after 25June2020–31December2021. Patients were indexed at the start of their most recent episode. Patients were non-persistent and discontinued the therapy associated with their most recent episode if there was ≥15-day gap in medication supply. A Cox proportional-hazards model estimated the discontinuation hazard between treatments. The gap periods and cohort definition were varied in sensitivity analyses. <h3>Results:</h3> The study included 66,576 patients (median age 46 years, 88.6% female). More eptinezumab-treated patients had chronic migraine (727/1074), ≥3 previous uses of acute (323/1074) or preventive (333/1074) therapies, and more prior treatment episodes than other treatment groups (3 [Q1–Q3, 2–5]). Based on a 15-day treatment gap, patients on subcutaneous CGRP mAbs had 32% (95%CI: 1.185, 1.494; erenumab) to 58% (95%CI: 1.418, 1.796; fremanezumab) higher discontinuation hazard than those receiving eptinezumab, with this relationship attenuated but significant with 30-day and 60-day treatment gaps. There was no significant difference in the discontinuation hazard between eptinezumab and onabotulinumtoxinA. Based on a 15-day treatment gap among patients who newly initiated therapy, the discontinuation hazard of subcutaneous CGRP mAbs remained significantly higher compared to eptinezumab and onabotulinumtoxinA. <h3>Conclusions:</h3> Eptinezumab had similar persistency with treatment to onabotulinumtoxinA, which was higher than subcutaneous CGRP mAbs. <b>Disclosure:</b> Dr. Talon has nothing to disclose. Christine Sullivan has received personal compensation for serving as an employee of Lundbeck. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck. Seema Soni-Brahmbhatt has nothing to disclose. Mr. Anderson has nothing to disclose. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Mr. Regnier has received personal compensation for serving as an employee of Lundbeck. Mr. Regnier has received personal compensation for serving as an employee of Novartis. Mr. Regnier has stock in Novartis.

Discrete Choice Experiment to Understand Japanese Patients' and Physicians' Preferences for Preventive Treatments for Migraine.

Self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) auto-injectors and non-CGRP oral medications are currently available for migraine prevention in Japan. This study elicited the preferences for self-injectable CGRP mAbs and non-CGRP oral medications and determined differences in the relative importance of auto-injector attributes for patients and physicians in Japan. Japanese adults with episodic (EM) or chronic (CM) migraine and physicians who treat migraine completed an online discrete choice experiment (DCE), asking participants to choose a hypothetical treatment they preferred between two self-injectable CGRP mAb auto-injectors and a non-CGRP oral medication. The treatments were described by seven treatment attributes, with attribute levels varying between questions. DCE data were analyzed using a random-constant logit model to estimate relative attribution importance (RAI) scores and predicted choice probabilities (PCP) of CGRP mAb profiles. A total of 601 patients (79.2% with EM, 60.1% female, mean age: 40.3years) and 219 physicians (mean length of practice: 18.3years) completed the DCE. About half (50.5%) of patients favored CGRP mAb auto-injectors, while others were skeptical of (20.2%) or averse (29.3%) to them. Patients most valued needle removal (RAI=33.8%), shorter injection duration (RAI=32.1%), and auto-injector base shape and need for skin pinching (RAI=23.2%). Most physicians (87.8%) favored auto-injectors over non-CGRP oral medications. Physicians most valued less-frequent dosing RAI=32.7%), shorter injection duration (30.4%), and longer storage outside the fridge (RAI=20.3%). A profile comparable to galcanezumab showed a higher likelihood of being chosen by patients (PCP=42.8%) than profiles comparable to erenumab (PCP=28.4%) and fremanezumab (PCP=28.8%). The PCPs of the three profiles were similar among physicians. Many patients and physicians preferred CGRP mAb auto-injectors over non-CGRP oral medications and preferred a treatment profile similar to galcanezumab. Our results may encourage physicians in Japan to consider patient preferences when recommending migraine preventive treatments.

Review of Tolerability of Fremanezumab for Episodic and Chronic Migraine.

Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) were the first class of medication specifically developed for the prevention of migraine. Fremanezumab is one of four CGRP mAbs currently available and is approved by the US Food and Drug Administration (FDA) for the preventative treatment of episodic and chronic migraines. This narrative review summarizes the history of fremanezumab development, the trials that led to its approval, and the later studies published evaluating its tolerability and efficacy. Evidence of fremanezumab for clinically significant efficacy and tolerability in patients with chronic migraine is especially important when considering the high level of disability, lower quality of life scores, and higher levels of health-care utilization associated with this condition. Multiple clinical trials demonstrated superiority of fremanezumab over placebo in terms of efficacy while demonstrating good tolerability. Treatment-related adverse reactions did not differ significantly compared to placebo and dropout rates were minimal. The most commonly observed treatment-related adverse reaction was mild-to-moderate injection site reaction, described as erythema, pain, induration, or swelling at the injection site.

New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy

Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP(-R) mAbs) and small-molecule CGRP receptor antagonists (gepants) are new mechanism-based prophylactic drugs developed to address the unmet needs of pre-existing migraine prophylactic medications. However, several uncertainties remain in their real-world applications. This is a narrative review of the literature on the use of CGRP-targeting novel therapeutics in specific situations, including non-responders to prior therapy, combination therapy, switching, and treatment termination. In the case of lack of available literature, we made suggestions based on clinical reasoning. High-quality evidence supports the use of all available anti-CGRP(-R) mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) in non-responders to prior therapy. There is insufficient evidence to support or reject the efficacy of combining CGRP(-R) mAbs or gepants with oral migraine prophylactic agents or botulinum toxin A. Switching from one CGRP(-R) mAb to another might benefit a fraction of patients. Currently, treatment termination depends on reimbursement policies, and the optimal mode of termination is discussed. New prophylactic drugs that target the CGRP pathway are promising treatment options for patients with difficult-to-treat migraine. Individualized approaches using a combination of new substances with oral prophylactic drugs or botulinum toxin A, switching between new drugs, and adjusting treatment duration could enhance excellence in practice.

Observational Analysis of the Costs Associated with Acute Treatment of Breakthrough Migraine Attacks in Medicaid Patients Using Preventive Therapies.

Medications for preventive treatment of migraine reduce migraine frequency, usually measured by a reduction in monthly migraine days (MMD), but generally do not eliminate the need for acute treatment. To assess the economic impact of treatment-related reductions in frequency, methodological guidance recommends capturing cost differences along the spectrum of MMD. Characterize monthly migraine medication costs along the spectrum of MMD for patients using calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) for prevention. Medicaid State Drug Utilization Data (SDUD) were used to identify formulations and per-unit costs for oral, intranasal, and parenteral migraine-specific medications for acute and preventive treatment used by fee-for-service (FFS) Medicaid enrollees in 2020. National drug codes of relevant therapies were used to match SDUD to formulation characteristics including substance, route of administration, and branded/generic marketing status. Mean per-unit cost and the formulation's share of total prescriptions were estimated. Monthly medication costs were modeled based on formulations' per-unit costs and frequency of acute medication use during clinical trials of CGRP mAbs. In the SDUD, there were 563,338 prescriptions for migraine-specific acute medications; triptans accounted for 97.37%. Triptan formulations prescribed were 83.78% oral tablet, 10.89% orally disintegrating tablet, 2.60% intranasal, and 2.73% parenteral. Dihydroergotamine accounted for < 1% of total prescriptions and had the highest per-unit cost ($443.50, branded intranasal). There were 97,119 prescriptions for CGRP mAbs, the majority for erenumab (45.73%) or galcanezumab (45.24%). Modeled monthly acute and preventive medication costs ranged from approximately $550 in patients with the fewest MMD treated with oral triptans to > $1500 in patients with the most MMD treated with dihydroergotamine. In consideration of the migraine-specific acute medications used in FFS Medicaid 2020, for patients using CGRP mAbs for prevention, medication costs may vary significantly with the number of breakthrough attacks treated per month and the type of migraine-specific acute therapy used.

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies.

Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment. Patients were visited at the time of the last mAb injection (V1) and 16 weeks later (V2). For control, 30 migraine patients without preventive drug therapy were included. We measured free CGRP plasma concentrations in the erenumab and fremanezumab group and total CGRP concentrations in the galcanezumab group. Free CGRP plasma concentrations did not change after treatment discontinuation [erenumab: V1 31.2 pg/mL (IQR 25.8−45.6), V2 30.3 pg/mL (IQR 22.9−47.6), p = 0.65; fremanezumab V1 29.4 pg/mL (IQR 16.4−61.9), V2 34.4 (19.2−62.0), p = 0.86]. Controls had similar CGRP values of 32.6 pg/mL (IQR 21.3−44.6). Total CGRP concentrations in the galcanezumab group were 5439.3 pg/mL (2412.7−6338.1) at V1, and decreased to 1853.2 pg/mL (1136.5−3297.0) at V2 (p < 0.001). Cessation of treatment with CGRP(-R) mAbs did not have an impact on the free-circulating CGRP concentrations. Total CGRP decreased significantly after three months of treatment discontinuation.

Advances in CGRP Monoclonal Antibodies as Migraine Therapy: A Narrative Review.

Migraine is a potentially disabling disorder, yet it remains underdiagnosed and undertreated. The release of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigemino-cerebrovascular system plays a vital role in the evolution of migraine. It enhances peripheral sensitization by mediating neurogenic inflammation and also influences central sensitization. The majority of the drug classes available for migraine prophylaxis are nonspecific and associated with numerous side effects and drug interactions. Anti-CGRP monoclonal antibodies (mAb) are an innovative therapeutic class that fulfills the need for more efficacious and tolerable preventive therapy. While erenumab is a mAb to the CGRP receptor, eptinezumab, fremanezumab, and galcanezumab bind to the CGRP molecule. They decrease the number of headache days and improve disability. Upper respiratory tract infection, nausea, constipation, pain at the site of injection, and fatigue are the associated side effects. CGRP mAbs are an excellent advancement in translational research and are a promising addition in migraine therapy. This article discusses the recent advances in the development of the CGRP mAbs.

Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review.

Numerous medications are used for the preventive treatment of chronic migraine (CM), including oral treatments, onabotulinumtoxinA (onabotA; BOTOX), and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). Despite substantial clinical trial evidence, less is published about the real-world experience of these treatments based on data routinely collected from a variety of sources. This systematic review assessed real-world evidence on the effectiveness and safety of preventive treatments for CM in adults. A systematic search of MEDLINE, Embase, and the Cochrane library with back-referencing and supplementary searches retrieved data published between January 2010 and February 2020. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. Search criteria included preventive medications for CM. Evidence was available for topiramate, onabotulinumtoxinA, CGRP mAbs (erenumab, galcanezumab, and fremanezumab). OnabotulinumtoxinA was most commonly assessed (55 studies), followed by erenumab (six studies), multiple CGRP mAbs (one study), and topiramate (one study). Long-term data (> 1year) were available for onabotulinumtoxinA only, with erenumab reported up 6months, topiramate up to 3months, and multiple CGRP mAbs up to 12months. Substantial data demonstrated that onabotulinumtoxinA reduces the number/frequency of headaches, concomitant acute medication use, and impact of headaches on well-being and daily activity. More limited evidence showed benefits for the same parameters with erenumab. Single studies suggested topiramate and multiple CGRP mAbs decrease the number/frequency of headaches and impact of headaches. To date, onabotulinumtoxinA is the only preventive treatment for CM that has long-term safety data in real-world settings reporting treatment-related adverse events of up to 3years. While substantial real-world evidence supports the long-term effectiveness and safety of onabotulinumtoxinA, real-world data on other preventive treatments of CM are currently limited to short term effectiveness due to their more recent approvals.

Efficacy and safety of monoclonal antibody against calcitonin gene-related peptide or its receptor for migraine patients with prior preventive treatment failure: a network meta-analysis

ObjectiveThe relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients.MethodsSeveral online databases including Ovid MEDILNE, Ovid EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 15, 2022. We included randomized clinical trials (RCT) of adult migraine patients with previous treatment failure that assessed any CGRP monoclonal antibody. The primary efficacy outcome was change in monthly migraine days (MMDs), and the primary safety outcome was treatment-emergent adverse events (TEAEs).ResultsOverall, seven studies totaling 3, 052 patients were included. Three-node analysis showed that CGRP mAbs was superior to CGRP receptor mAbs in reducing MMDs (MD: -1.55, 95% CrI: − 2.43 to − 0.44) and improving at least 50% response rates (RR: 1.52, 95% CrI: 1.04 to 2.21). Nine-node analysis showed galcanezumab 240 mg ranked first in reducing MMDs (MD -4.40, 95% CrI − 7.60 to − 1.19) and improving 50% response rates (RR: 4.18, 95% CrI: 2.63 to 6.67). Moreover, treatment with fremanezumab or eptinezumab 300 mg provides a significant advantage over erenumab 140 mg regarding an improved response rate of at least 50%. The analysis did not show difference in incidences of TEAEs and serious adverse events in any of the comparisons.ConclusionsIt appears that CGRP mAbs, especially galcanezumab 240 mg, monthly fremanezumab, and eptinezumab 300 mg, seem to be the best choice for the treatment of migraine patients with previous treatment failures. This finding also calls for future research that examine the associations between these medications in migraine therapy among the same patient group to testify the present findings.

Measuring interictal burden among people affected by migraine: a descriptive survey study

BackgroundPrevious research has extensively documented the impact of migraine episodes (‘ictal’) on patients’ health-related quality of life. Few studies have looked at the impact of migraine on migraine-free days (‘interictal’). This study was designed to describe interictal burden of migraine in a mixed group of people affected by migraine and to explore patient characteristics associated with interictal burden.MethodsPeople with migraine in the United States (US) and Germany were recruited for a cross-sectional online survey, including a subgroup treated with calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). The survey included the Migraine Interictal Burden Scale (MIBS-4), Headache Impact Test (HIT-6), and items measuring patient demographics, clinical and treatment background. Data were analyzed using descriptive statistics and linear regression.ResultsFive hundred six people with migraine completed the survey (US: n = 257; Germany: n = 249), of whom 195 had taken a CGRP mAb for three or more months. Participants had a mean of 8.5 (SD = 6.4) Monthly Migraine Days (MMD) and 10.4 (SD = 7.1) Monthly Headache Days (MHD). The mean MIBS-4 score was 6.3 (SD = 3.4), with 67% reporting severe interictal burden (MIBS-4: ≥5). The mean HIT-6 score was 65.3 (SD = 6.0), with 86% reporting severe migraine impact (HIT-6: ≥60). MIBS-4 was correlated with the HIT-6 (r = 0.37), MMD and MHD (both r = 0.27). The HIT-6, MMD, MHD, CGRP mAb treatment, and depression all had an independent positive association with the MIBS-4.ConclusionTwo-thirds of the study sample reported substantial interictal burden. Whilst interictal burden was associated with migraine frequency and impact of migraine attacks, study results also show it represented a distinct aspect of the overall disease burden. Study findings further indicate unique associations between interictal burden and depression. A unique positive association between interictal burden and CGRP mAb treatment suggests a remaining unmet need among people affected by migraine treated with CGRP mAb.

Patient characteristics and treatment utilization among patients with migraine initiating self-injectable calcitonin gene-related peptide monoclonal antibody and novel acute medication

Objective This study describes patient characteristics and utilization of recently approved novel acute medication and calcitonin gene-related peptide (CGRP) monoclonal antibodies. Methods This retrospective observational study utilized the IBM MarketScan Research Database and Optum’s Clinformatics Data Mart from May 2017 through December 2020 (index period). Adult patients initiating self-injectable CGRP monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab) and novel acute migraine medications (lasmiditan, rimegepant, ubrogepant) with: (a) ≥3 months overlap between the index medication and second medication initiated along with it; (b) ≥1 claim for migraine diagnosis; and (c) continuous medical and pharmacy benefits 12 months pre- and 3 months post-index were included. Data are presented descriptively. Results A total of 2840 patients from the MarketScan database and 657 patients from the Optum database were included. Identified patients’ (MarketScan/Optum) mean age was 44.7/51.2 years; they were mostly women (88.8%/87.7%); a majority had a chronic migraine diagnosis (64.4%/71.4%) and were prescribed both preventive and acute treatments for migraine in the pre-index period. Most patients received a combination of both preventive and acute medications binding CGRP receptors (43.6%/59.0%) or preventive medication binding CGRP ligands and acute medication binding CGRP receptors (51.9%/34.9%). Mean (SD) number of days of concomitant use of CGRP and novel acute medications were: MarketScan, 29.1 (18.7); Optum, 31.8 (20.4). Prescribing patterns were similar across healthcare provider types within each database. Conclusions Understanding patient characteristics and treatment utilization patterns among patients prescribed both a CGRP mAb and novel acute medication may provide valuable insight regarding migraine treatment selection for healthcare decision makers.