Monoclonal Calcitonin Gene-related Peptide Research Articles

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.

Monoclonal CGRP- (R) antibodies for the prevention of migraine

A new era in migraine prophylaxis has begun with the launch of antibodies blocking the Calcitonin-Gene Related Peptide (CGRP) pathway. These substances act across the entire frequency spectrum of migraine and have a tolerability superior to any other class of migraine preventatives based on our clinical and experimental knowledge of a 5- year period of use. Their superior tolerability profile may be due to their specificity. New questions have also arrived with these drugs ranging from the duration of therapy and treatment pause to the question which monoclonal antibodies (mAb) for which patient - a question which we cannot answer at this stage. Nevertheless, CGRP – ® mAbs offer a class of migraine prophylactics with significant advantages over older medications.

Preclinical Studies of Posttraumatic Headache and the Potential Therapeutics

Posttraumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache developed within 7 days after head injury, and in a substantial number of patients PTH becomes chronic and lasts for more than 3 months. Current medications are almost entirely relied on the treatment of primary headache such as migraine, due to its migraine-like phenotype and the limited understanding on the PTH pathogenic mechanisms. To this end, increasing preclinical studies have been conducted in the last decade. We focus in this review on the trigeminovascular system from the animal studies since it provides the primary nociceptive sensory afferents innervating the head and face region, and the pathological changes in the trigeminal pathway are thought to play a key role in the development of PTH. In addition to the pathologies, PTH-like behaviors induced by TBI and further exacerbated by nitroglycerin, a general headache inducer through vasodilation are reviewed. We will overview the current pharmacotherapies including calcitonin gene-related peptide (CGRP) monoclonal antibody and sumatriptan in the PTH animal models. Given that modulation of the endocannabinoid (eCB) system has been well-documented in the treatment of migraine and TBI, the therapeutic potential of eCB in PTH will also be discussed.

Can calcitonin gene-related peptide monoclonal antibody improve migraine and restless legs syndrome?

BackgroundA significant association between migraine and restless legs syndrome (RLS) has been reported, and their coexistence is not uncommon. We report a patient with concomitant migraine and RLS who showed improvement of both migraine and RLS symptoms after treatment with galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody. Case presentationA 47-year-old woman had been treated in our outpatient headache clinic for migraine without aura. She had RLS since childhood and had been treated with dopamine agonists and α2δ ligands. Over the past 2 months, the patient suffered from frequent migraine headaches and worsening RLS symptoms, despite ongoing treatment. Therefore, galcanezumab was started. After 1 month, the number of headache days decreased from 20 to 4, and her score on the International RLS Study Group Rating Scale improved from 38 to 10. Her photo/phono/osmo-phobia were also markedly improved. The efficacy of galcanezumab for both headache and RLS was sustained over 5 months. ConclusionWe report a case of improvement of both migraine and RLS after treatment with CGRP monoclonal antibody. Additional studies are needed to clarify how CGRP antagonism affects RLS symptoms in patients with migraine and RLS comorbidity.

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.

Real-World experience of interictal burden and treatment in migraine: a qualitative interview study.

BackgroundThe debilitating nature of migraine attacks is widely established; however, less is known about how the interictal burden (i.e., how patients are affected in-between migraine episodes) of migraine impacts on patients’ health-related quality of life (HRQL). Acute and preventive treatments may lift the burden of the disease, but they often have unwanted side effects and limited effectiveness. The objective of this study was to understand the interictal burden of migraines, from the patient perspective, and to explore patient experience with migraine treatments.MethodsParticipants (n=35) with a self-reported diagnosis of migraine were recruited in the US, UK and Canada, including a subgroup of patients who had taken calcitonin gene-related peptide monoclonal antibody (CGRP mAb) treatment for at least three months. Participants completed a background questionnaire, followed by a semi-structured interview via telephone or video call. The interviews explored patients’ migraine symptoms, perception of interictal burden and treatment experience. The interview transcripts were analysed using thematic analysis.ResultsThe most reported migraine symptom was migraine pain, followed by aura, sensory sensitivity and nausea. Most participants reported interictal impact on HRQL, lifestyle changes they made to avoid triggers or in anticipation of an attack, impacts on work, career, daily activities and relationships. Emotional impacts were reported by all participants, including anger, depression, anxiety and hopelessness. Many participants who took preventive treatments reported improvements in HRQL and functioning but still experienced breakthrough attacks. Among patients who took CGRP mAbs, participants noted varying consistency of treatment effectiveness between treatment administrations.ConclusionThis study detailed the additional HRQL impact of migraine in-between migraine attacks and described the unmet need for effective treatment options to prevent and mitigate migraine attacks.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01429-5.

Erenumab in chronic migraine: Experience from a UK tertiary centre and comparison with other real-world evidence.

Background and purposeChronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene‐related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real‐world data in tertiary settings.MethodsWe audited our first 92 patients (n = 73 females) with severely disabling chronic migraine who were given monthly erenumab 70 mg sc for 6 months between December 2018 and December 2019.ResultsAt 3 months, monthly migraine days were significantly reduced by a median of 4 days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported.ConclusionsOur real‐world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.

Real-World Evidence for the Safety and Efficacy of CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA Treatment for Migraine Prevention in Adult Patients With Chronic Migraine.

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) target different migraine pathways, therefore, combination treatment may provide additional effectiveness for the preventive treatment of chronic migraine (CM) than either treatment alone. The objective of this study was to collect real-world data to improve the understanding of the safety, tolerability, and effectiveness of adding a CGRP mAb to onabotulinumtoxinA treatment for the preventive treatment of CM.Methods: This was a retrospective, longitudinal study conducted using data extracted from a single clinical site's electronic medical records (EMR) of adult patients (≥18 years) with CM treated with ≥2 consecutive cycles of onabotulinumtoxinA before ≥1 month of continuous onabotulinumtoxinA and CGRP mAb (erenumab, fremanezumab, or galcanezumab) combination treatment. Safety was evaluated by the rate of adverse events (AE) and serious adverse events (SAE). The proportion of patients who discontinued either onabotulinumtoxinA, a CGRP mAb, or combination treatment, and the reason for discontinuation, if available, was collected. The effectiveness of combination preventive treatment was assessed by the reduction in monthly headache days (MHD). Outcome data were extracted from EMR at the first CGRP mAb prescription (index) and up to four assessments at ~3, 6, 9, and 12 months post-index. The final analyses were based on measures consistently reported in the EMR.Results: EMR were collected for 192 patients, of which 148 met eligibility criteria and were included for analysis. Erenumab was prescribed to 56.7% of patients, fremanezumab to 42.6%, and galcanezumab to 0.7%. Mean (standard deviation [SD]) MHD were 20.4 (6.6) prior to onabotulinumtoxinA treatment and 14.0 (6.9) prior to the addition of a CGRP mAb (baseline). After real-world addition of a CGRP mAb, there were significant reductions in MHD at the first assessment (~3 months) (mean −2.6 days/month, 95% CI −3.7, −1.4) and at all subsequent visits. After ~12 months of continuous combination treatment, MHD were reduced by 4.6 days/month (95% CI −6.7, −2.5) and 34.9% of patients achieved ≥50% MHD reduction from index. AEs were reported by 18 patients (12.2%), with the most common being constipation (n = 8, 5.4% [onabotulinumtoxinA plus erenumab only]) and injection site reactions (n = 5, 3.4%). No SAEs were reported. Overall, 90 patients (60.8%) discontinued one or both treatments. The most common reason for discontinuing either treatment was lack of insurance coverage (40%); few (~14%) patients discontinued a CGRP mAb and none discontinued onabotulinumtoxinA due to safety/tolerability.Conclusion: In this real-world study, onabotulinumtoxinA was effective at reducing MHD and the addition of a CGRP mAb was safe, well-tolerated and associated with incremental and clinically meaningful reductions in MHD for those who stayed on the combination treatment. No new safety signals were identified. Of those who discontinued, the majority reported lack of insurance coverage as a reason. Prospective real-world and controlled trials are needed to further evaluate the safety and potential benefits of this combination treatment paradigm for people with CM.

A Review of Eptinezumab Use in Migraine.

We present a review of the efficacy and safety profile of eptinezumab (also known by the brand name Vyepti), a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) developed by Lundbeck Seattle BioPharmaceuticals, Inc., that received its first approval in the USA on 21 February 2020 for the preventive treatment of migraine in adults. It is administered by an intravenous infusion at a 100 mg dose every 3 months and shows no drug interactions.Studies have shown that eptinezumab is an effective preventative medication in migraine which starts showing its effect from day 1 of its administration, which maintains a consistent level of efficacy through a year of its treatment at doses 100 mg and 300 mg. It was found to be effective at reducing time to headache pain freedom during acute migraine attacks as well.Eptinezumab is a relatively safe drug for the prevention of migraines with treatment-related adverse events occurring at a low frequency. They bear a safe profile in patients with comorbidities like obesity and type 1 diabetes. The most frequent adverse events observed were nasopharyngitis, upper respiratory tract infections (URTIs), and sinusitis and were usually mild. The development of anti-drug antibodies was common, but they declined to undetectable levels with continued dosing and did not appear to impact the overall safety profile of the drug. Further studies are needed to assess long-term safety, use in different patient populations, and to compare its efficacy to other drugs of its class.

Treatment with the monoclonal calcitonin gene-related peptide receptor antibody erenumab: A real-life study.

Background and purposeNew prophylactics for migraine, targeting calcitonin gene‐related peptide (CGRP), have recently emerged. Real‐world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real‐world setting, in order to determine which patients may be considered responders in clinical practice.MethodsAll erenumab‐treated patients (n = 100) completed a time‐locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non‐migrainous headache days, days of acute medication use (MAMD), well‐being and coping with pain were assessed for a 6‐month period. The primary outcome was reduction in MMD compared to baseline.ResultsThe numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p < 0.001), while general well‐being (p < 0.001) and coping with pain (p < 0.001) also improved. Of all patients, 36% had an MMD reduction of ≥50% in ≥3/6 months, and 6% had such a reduction in all 6 months. For a ≥30% MMD reduction, the figures were 60% and 24%, respectively. Almost 90% of patients with an average MMD reduction of ≥30% over the first 3 months had a sustained response in the last 3 months. In addition, 20% of patients without an initial response (average <30%), had a delayed response (average ≥30%) in the last 3 months.ConclusionErenumab was effective in migraine patients who were highly refractory to previous prophylactics. As a practical guideline, we propose that treatment be continued for at least 6 months and that patients with a ≥30% MMD reduction in at least half of the treatment period should be considered to be responders.

Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: A narrative review.

Headache is a near-universal sequela of idiopathic intracranial hypertension (IIH). The aim of this paper is to report current knowledge of headache in IIH and to identify therapeutic options. Disability in IIH is predominantly driven by headache; thus, headache management is an urgent and unmet clinical need. At present, there is currently no scientific evidence for the directed use of abortive or preventative headache therapy. A detailed search of the scientific literature and narrative review was performed. Headache in IIH is driven by raised intracranial pressure (ICP) and reduction of ICP has been reported in some studies to reduce headache. Despite resolution of papilledema and normalization of raised ICP, a majority suffer persistent post-IIH headache. The lack of evidence-based management approaches leaves many untreated. Where clinicians attempt to manage IIH headache, they use off-label therapies to target the prevailing headache phenotype. A recent prospective open-label study demonstrated the effective use of a calcitonin gene-related peptide monoclonal antibody therapy in IIH for persistent post-IIH headache. There is overwhelming evidence of the headache burden in IIH. Studies are required to investigate the biological foundations of headache related to ICP and to develop treatments specifically directed to manage headache in IIH.

Calcitonin Gene-Related Peptide Monoclonal Antibody Versus Botulinum Toxin for the Preventive Treatment of Chronic Migraine: Evidence From Indirect Treatment Comparison.

Background: The previously approved botulinum toxin and nowadays promising calcitonin gene-related peptide (CGRP) monoclonal antibody have shown efficacy for preventing chronic migraine (CM). However, there is no direct evidence for their relative effectiveness and safety. In this study, we conducted an indirect treatment comparison to compare the efficacy and safety of CGRP monoclonal antibody with botulinum toxin for the preventive treatment of chronic migraine. Methods: Up to August 31, 2020, we systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials (Central). Weighted mean difference (WMD) and relative risk (RR) were used to evaluate clinical outcomes. Indirect treatment comparison (ITC) software was used to conduct indirect treatment comparison. Results: Ten studies were pooled with 6,325 patients in our meta-analysis. Both botulinum toxin and CGRP monoclonal antibody demonstrated favorable efficacy in the change of migraine days, headache days, HIT-6 score, and 50% migraine responder rate compared with placebo. In indirect treatment comparison, CGRP monoclonal antibody was superior to botulinum toxin in the frequency of acute analgesics intake (WMD = −1.31, 95% CI: −3.394 to 0.774, p = 0.02113), the rate of treatment-related adverse events (AEs) (RR = 0.664, 95% CI: 0.469 to 0.939, p = 0.04047), and the rate of treatment-related serious adverse events (RR = 0.505, 95% CI: 0.005 to 46.98, p < 0.001). Conclusion: For chronic migraine patients, CGRP monoclonal antibody was slightly better than botulinum toxin in terms of efficacy and safety. In the future, head-to-head trials would be better to evaluate the efficacy and safety between different medications in the prevention of chronic migraine.

Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments

BackgroundGalcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown.MethodsCONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures.ResultsThe most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (all p < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (all p < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (all p < 0.01).ConclusionsIn this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability.Trial registrationClinicalTrials.gov NCT03559257 (CONQUER).

Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review.

IntroductionCombination use of onabotulinumtoxinA and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) has the potential to be more effective than either therapy alone for migraine prevention.MethodsThis retrospective, longitudinal chart review included adults with chronic migraine treated at one clinical site with ≥ 2 consecutive cycles of onabotulinumtoxinA and ≥ 1 month of subsequent combination treatment with CGRP mAbs. Charts at time of mAb prescription (baseline) and up to four visits ~ 3, 6, 9, and 12 months post-baseline were reviewed for safety, tolerability, and outcome measures (monthly headache days [MHDs], headache intensity, and migraine-related disability [MIDAS]).ResultsOf 300 charts reviewed, 257 patients met eligibility criteria (mean age: 50 years; 82% women). Average headache frequency was 21.5 MHDs before initiation of onabotulinumtoxinA and 12.1 MHDs before adding CGRP mAb therapy. Prescribed mAbs were erenumab (78%), fremanezumab (6%), and galcanezumab (16%). Over the entire study, patients discontinued CGRP mAb more frequently than onabotulinumtoxinA (23 vs. 3%). Adverse events occurred in 28% of patients, most commonly constipation (9%). Compared with onabotulinumtoxinA alone (baseline), MHDs decreased significantly at all visits (mean decrease: 3.5–4.0 MHDs over ~ 6–12 months of combination treatment); 45.1% of patients had clinically meaningful improvement in migraine-related disability (≥ 5-point reduction in MIDAS score) after ~ 6 months.ConclusionsIn this real-world study, combination treatment with onabotulinumtoxinA and CGRP mAbs was well tolerated, with no new safety signals identified, and was associated with additional clinically meaningful benefits. More real-world and controlled trials should be considered to further assess safety and potential benefits of combination treatment. Video abstract: Real-world data suggests that CGRP inhibitors improve onabotulinumtoxinA efficacy for chronic migraine (MP4 20,067 kb)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00264-x.

Migraine with Brainstem Aura Accompanied by Disorders of Consciousness

Migraine with brainstem aura (MBA) accompanied by disorders of consciousness (DOC) is a rare subtype of migraine. The pathophysiology of MBA with DOC has not been elucidated yet. Some patients have a family history of migraine, and women are more affected than men. The aura symptoms are diverse; however, when MBA is combined with DOC, the clinical manifestations are more complicated. Coma is the most common clinical manifestation. The overall duration of the patient’s DOC is short and can often return to normal within half an hour. Headache often occurs after regaining consciousness and can also occur at the same time as DOC. The most common headache is located at the occipital region. Although DOC is reversible, considering the current small number of cases, we still need to improve our understanding of the disease to avoid misdiagnosis. The MBA patient’s electroencephalogram and cerebral blood flow perfusion may have transient changes and may return to normal in the interictal period or after the DOC. Although triptans have traditionally been contraindicated in MBA under drug instructions, the evidence of basilar artery constriction, as postulated in MBA, is lacking. Lasmiditan is currently the first and only 5-HT 1F receptor agonist approved by the Food and Drug Administration. The calcitonin gene-related peptide receptor antagonists and monoclonal antibody therapies may be the most promising for future consideration. Here, the pathophysiology, clinical manifestations, diagnostic tools, and treatment progress for MBA with DOC are reviewed.

Efficacy of Erenumab in the Treatment of Trigeminal Neuralgia: A Retrospective Case Series.

Trigeminal neuralgia (TN) is a chronic, often refractory, pain condition, which adversely affects the lives of patients. Current treatments are only mildly effective. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have been successfully studied in the treatment of migraines. CGRP plays a role in both TN and migraine. It is prudent to attempt CGRP monoclonal antibody therapy in TN. Erenumab, a human anti-CGRP monoclonal antibody medication, modulates CGRP, which is elevated in patients with TN. The primary objective of this study was to evaluate the efficacy of erenumab for patients with TN. Retrospective analysis was performed on data collected from 10 patients diagnosed with TN and treated with erenumab for 6 months. Pain was tracked using a numeric pain rating scale (NPRS) from 0 to 10. The effect of erenumab on NPRS after 6 months' time was the primary end point. Secondary end points included side effects to therapy, improvement in headache frequency in those with comorbid migraine, evaluating mood following therapy, and global mood improvement using scale (worse, no change, improved). Nine of 10 patients (90.0%) reported improvement in pain severity and in global mood improvement. Three patients reported resolution of anxiety and/or depression. Side effects were minimal, with 3 patients reporting constipation, injection site reactions, or both. Based on these results, erenumab appears to be an efficacious treatment option for patients with refractory TN. Patients experienced improvement in pain, reduced frequency of headache, and improvement in mood. Treatment was well tolerated with only mild side effects reported. This study provides Class IV evidence that erenumab increases the probability of improved pain control in patients with medication-resistant TN.

Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis.

Background: The optimal monoclonal antibody against calcitonin gene-related peptide (CGRP) for adult patients with migraine has yet to be determined. Therefore, we aimed to compare the effectiveness of different monoclonal antibodies against CGRP or its receptor for adult patients with migraine through a network meta-analysis of randomized controlled trials. Methods: We systematically searched the MEDILNE, Embase, ClinicalTrials.gov, and Cochrane Library databases for relevant publications from inception until October 30, 2020. Only randomized clinical trials of adults with migraine that assessed any calcitonin gene-related peptide monoclonal antibody and reported clinical outcomes were included. The primary outcomes were changes in monthly migraine days and treatment-emergent adverse events Results: We initially retrieved 2,070 publications, and ultimately, 18 randomized clinical trials totaling 8,926 patients were included. In terms of efficacy, eptinezumab (MD −1.43, 95% CrI −2.59 to −0.36), erenumab (MD −1.61, 95% CrI −2.40 to −0.84), fremanezumab (MD −2.19, 95% CrI −3.15 to −1.25), and galcanezumab (MD −2.10, 95% CrI −2.76 to −1.45) significantly reduced MMDs compared with placebo. In terms of safety, only galcanezumab increased the incidences of TEAEs (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared with placebo. Conclusion: Most drugs performed similarly and were superior to placebo in most of our analyses. Further head-to-head research on different types of CGRP monoclonal antibodies is necessary to validate the present findings.

Eptinezumab: A calcitonin gene-related peptide monoclonal antibody infusion for migraine prevention.

This article seeks to analyze the clinical trials concerning the newly approved eptinezumab to assess its efficacy, safety, and application to current clinical practice. The Institute of Health US National Library of Medicine Clinical Trials, PubMed, and Cochrane Library databases were searched for relevant abstracts, journal articles, and other published sources. Search terms included eptinezumab, Vyepti®, and ALD403. Relevant English-language articles were evaluated and included in the narrative. Two randomized controlled trials compared quarterly infusions of eptinezumab 100 mg, eptinezumab 300 mg, and placebo in chronic and episodic migraine sufferers. In episodic migraine, eptinezumab resulted in a reduction of approximately 4 monthly migraine days, which was significant compared to placebo. In chronic migraine, eptinezumab reduced monthly migraine days by approximately 8 days, also significant compared to placebo. More patients who received eptinezumab experienced at least 75% reduction in monthly migraine days compared to placebo, resulting in a number needed to treat as low as 6, depending on the study population and the dose. The preventive impact was noticed day one post-infusion. The most common treatment-emergent adverse events were nausea and fatigue, and there was a low incidence of hypersensitivity or study withdrawal. Eptinezumab is the fourth Calcitonin Gene-related Peptide monoclonal antibody to receive Federal Drug Administration approval. Its delivery as a quarterly infusion sets it apart from the other agents in this class. As an infusion, eptinezumab has a quick onset of action that may prove especially beneficial to those with severe or refractory episodic or chronic migraines, despite the perceived increased direct and indirect cost of an infusion.