Monoclonal Calcitonin Gene-related Peptide Research Articles

Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database.

Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines. The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.

Patients’ Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb)

Patients’ Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb)

Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice

The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE−/−) mice to generate double-knockout ApoE−/−:CGRP−/− mice lacking alpha CGRP. ApoE−/−:CGRP−/− mice exhibited larger atherosclerotic plaque areas, peritoneal macrophages with enhanced migration functions, and elevated levels of the inflammatory cytokine tumor necrosis factor (TNF)-⍺. Thus, we also explored whether inhibiting TNF-⍺ could improve atherosclerosis in ApoE−/−:CGRP−/− mice by administering etanercept intraperitoneally once a week (5 mg/kg) alongside a high-fat diet for 2 weeks. This treatment led to significant reductions in aortic root lesion size, atherosclerotic plaque area and macrophage migration in ApoE−/−:CGRP−/− mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE−/−:CGRP−/− mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE−/− mice. ApoE−/− mice were subcutaneously administered galcanezumab at an initial dose of 50 mg/kg, followed by a dose of 30 mg/kg in the second week. Galcanezumab administration did not affect systolic blood pressure, serum lipid levels, or macrophage migration but led to a significant increase in lipid deposition at the aortic root. These findings suggest that alpha CGRP plays a critical role in inhibiting the progression of atherosclerosis.

Monoclonal antibody therapy for refractory chronic migraine-like headache related Lyme disease: a case report

IntroductionLyme disease, caused by Borrelia burgdorferi, can lead to diverse neurological manifestations, including headache. While most Lyme-associated headaches resolve with antibiotics, some may evolve into a refractory chronic migraine-like syndrome. We present a case of post-Lyme chronic migraine-like headache responsive to galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.Case ReportA 42-year-old woman developed chronic migraine-like headaches following treatment for Lyme neuroborreliosis. The headaches were refractory to standard preventive therapies and only partially responsive to onabotulinumtoxinA. Administration of galcanezumab resulted in significant reduction of headache frequency, intensity, and impact on daily activities.CommentThis case highlights the potential of CGRP-targeted therapies for persistent migraine-like headaches following Lyme neuroborreliosis. The favorable response to galcanezumab suggests a role for CGRP in the pathophysiology of post-Lyme headache. While further research is needed to establish efficacy and safety, clinicians should consider CGRP monoclonal antibodies for chronic migraine-like headaches refractory to standard treatments in the post-infectious phase of Lyme disease. The emergence of chronic migraine-like headaches following Lyme neuroborreliosis and the response to a CGRP monoclonal antibody in this case underscore the importance of considering targeted migraine therapies in the management of persistent headaches after antibiotic treatment. This report contributes to the understanding of Lyme disease sequelae and potential treatment options, warranting further investigation into the utility of CGRP-targeted therapies in this context.

The Effect of Calcitonin Gene-Related Peptide Monoclonal Antibodies on Quality of Life among Migraine Patients: Pilot Study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics.

Migraine has a negative impact on patients' quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody. A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period. The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline. For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.

Use of Calcitonin Gene-Related Peptide Monoclonal Antibodies for the Treatment of Migraines in Individuals With Multiple Sclerosis.

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. 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. 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. 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.

Effect of CGRP inhibitors on interictal cerebral hemodynamics in individuals with migraine.

Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics. In 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated. CA was similar off and on treatment, in the MCA (p = 0.42) and PCA (p = 0.72). CVR was also unaffected by treatment, in the MCA (p = 0.38) and PCA (p = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1-12.4; p = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9-10.3; p = 0.04). Dynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.

Characteristics of Patients Receiving Co-prescriptions for a Calcitonin Gene-related Peptide Monoclonal Antibody and a Gepant: A Retrospective, Observational Study (P8-12.003)

Characteristics of Patients Receiving Co-prescriptions for a Calcitonin Gene-related Peptide Monoclonal Antibody and a Gepant: A Retrospective, Observational Study (P8-12.003)

Understanding Patients’ Journeys Prior to Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention in the United States (P8-12.008)

Understanding Patients’ Journeys Prior to Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention in the United States (P8-12.008)

Interictal Burden Before Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention (P9-12.003)

Interictal Burden Before Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention (P9-12.003)

Anti-CGRP-based Migraine Medications: A Comprehensive Overview

In the early 1990s, the neuropeptide calcitonin gene-related peptide (CGRP) was identified as a key messenger in the pathophysiology of migraine and emerged as a treatment target, fundamentally transforming our approach to migraine therapy. While previous prophylactic drugs were non-specific and often caused intolerable side effects, the discovery of CGRP marked the advent of a new era in migraine treatment. The two main classes of CGRP-specific migraine treatments are monoclonal antibodies that bind to CGRP or the CGRP receptor, and CGRP receptor antagonists, the so-called gepants. Extensive clinical trials have conclusively demonstrated the safety, tolerability, and efficacy of monoclonal CGRP(-receptor) antibodies in the prophylactic treatment of both episodic and chronic migraine. The same positive results apply to the use of various gepants. They have proven to be not only an effective alternative to triptans in acute migraine therapy but also promising options for continuous use as prophylactic treatments. In this review, we aim to present the current state of research on CGRP-specific migraine therapy and insights in real-world data from the first years after their launch in clinical practice.

Treatment Patterns, Healthcare Resource Utilization, and Direct Costs Among Patients Initiating Concomitant Use of a Calcitonin Gene-Related Peptide Monoclonal Antibody (CGRP mAb) and Novel Acute Medication in the United States.

To describe treatment patterns, all-cause and migraine-related healthcare resource utilization (HCRU), and direct costs among people with migraine treated with concomitant calcitonin gene-related peptide monoclonal antibody (CGRP mAb) and novel acute migraine medications (ubrogepant, rimegepant, lasmiditan) in the United States (US). This retrospective, observational cohort study utilized data from the IBM MarketScan® Research Databases and included adults initiating CGRP mAb or novel acute migraine medication as index medications between May 01, 2018, and Feb 28, 2021. All-cause and migraine-related HCRU (number of visits) and costs at baseline (12 months pre-index) and at follow-up (12 months post-index) were descriptively analyzed; differences between values at follow-up and baseline were reported. Of 4,167 included in the analysis (mean [SD] age: 43.7 [11.2] years), 89.2% were women, and 59.7% had chronic migraine. Adherence to the indexed CGRP mAb was 47% (using proportion of days covered [PDC]) and 80.1% (using medication possession ratio [MPR]); mean (SD) persistence was 273.4 (115.3) days). At follow-up, 43.9% of the patients discontinued their index preventive medication of which 80.2% switched to a different preventive migraine medication; 17.0% restarted their index preventive medication. Reductions in all-cause inpatient HCRU, all-cause inpatient and outpatient costs, and migraine-related outpatient HCRU were observed at follow-up vs. baseline, whereas increases in all-cause outpatient HCRU, all-cause medication costs, migraine-related inpatient HCRU, and migraine-related inpatient, outpatient, and medication costs were observed. In this study, observed treatment patterns with the indexed CGRP mAb were consistent with prior reports. Concomitant treatment with CGRP mAb and novel acute migraine medications led to reductions in some outcomes of HCRU and direct costs, however, increases were also observed. Treatment utilization, reductions in HCRU and cost savings identified in this study in favor of concomitant CGRP mAb and novel acute medications may help clinicians and other healthcare decision makers assessing appropriate therapeutic options for migraine management.

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.

Long-Term Effect of Switching From an Anti-CGRP Receptor to an Anti-CGRP Ligand Antibody in Treatment-Refractory Chronic Migraine: A Prospective Real-World Analysis

In migraine patients with a poor response to a calcitonin gene-related peptide monoclonal antibody against the receptor, switching to a calcitonin gene-related peptide monoclonal antibodies against the ligand may be beneficial. This was a long-term real-world prospective analysis conducted in treatment-refractory chronic migraine patients coming from two large tertiary referral headache centres, who did not achieve a meaningful response to erenumab and were switched to fremanezumab. Responders to fremanezumab were considered those who achieved at least 30% reduction in monthly migraine days by month 3, compared to the post-erenumab baseline. Secondary efficacy and disability outcomes were analysed. Thirty-nine patients (female n = 32, 82.1%; median age: 49 years old, IQR = 29.0–56.0) were included. After three months of treatment with fremanezumab, ten out of 39 patients (25.6%) were considered responders. Four of the 11 patients who continued fremanezumab became responders at month 6, increasing the number of responders to 14 patients (35.9%). Responders received a median of 12 injections (IQR = 9.0–18.0) at the time of the analysis. After the last treatment, 13 patients (33.3%) remained responders. The number of mean monthly migraine days significantly decreased from 21.4 at baseline (IQR = 10.7–30.0) to 8.6 (IQR = 3.8–13.9) at the last follow-up. Painkillers intake and HIT-6 score were significantly reduced at the last follow-up. About 1/3 of patients with treatment refractory chronic migraine who have a disappointing response to erenumab and switch to fremanezumab, obtained a meaningful and sustained improvement of their migraine load over time, supporting the appropriateness of this therapeutic approach in clinical practice.

The Management of High-Frequency Episodic and Chronic Migraines with Calcitonin Gene-Related Peptide Monoclonal Antibody

Introduction. High prevalence of migraine and its impact on quality of life requires the development of original agents. In 2020, fremanezumab, a new calcitonin gene-related peptide monoclonal antibody was authorized in Russia.
 Objective: to evaluate safety and effectiveness of fremanezumab in patients with high-frequency episodic migraine (HF EM) and chronic migraine (CM).
 Materials and methods. We assessed 60 patients at the age of 35.5 8.96 years (85%, females) with HFEM and CM with and without aura who were either receiving preventive treatment or not. Fremanezumab was administered subcutaneously at a single dose of 675 mg. The study participants were followed-up for efficacy in 3 months. The investigators assessed change in the number of days with headache per month as well as headache intensity, its impact on the daily activities, anxiety, and depression.
 Results. By the end of month 3 post dosing, the number of days with headache decreased by 50% in 76.7% of participants where 77.8% of individuals suffered from HF EM and 72.7% of individuals had CM while headache intensity decreased in all the patients equally. No response (decrease in the number of days with headache by 30%) was reported in 15% of participants including 14.8% of individuals with HF EM and 15.2% of individuals with CM. By the end of study month 3, 81% of participants demonstrated no anxiety symptoms and 79% of participants showed no depression with significant MIDAS and HIT-6 score decline in both groups. Only 3 (5%) patients noted adverse events (redness, itching at the administration site).
 Conclusion. We documented higher fremanezumab safety and effectiveness in patients with EM and CM in real-world practice as compared to fremanezumab safety and efficacy in randomized clinical trials. A single dose of fremanezumab (675 mg) resulted in effective migraine prevention, decline in comorbid anxiety and depression, and improved quality of life during 3-month follow-up.

Real-world treatment patterns and healthcare resource utilization among migraine patients: a German claims database analysis

AimsDespite migraine being one of the most common neurological diseases, affected patients are often not effectively treated. This analysis describes the burden of migraine in Germany and assesses real-world treatment patterns and healthcare resource utilization (HCRU) of preventive-treated migraine patients from the perspective of Statutory Health Insurance.MethodsA retrospective analysis was conducted using InGef Research Database claims data from 2018–2019. Migraine patients were stratified into cohorts by acute and preventive treatment status. Patients on preventive treatment were further stratified according to the type of prophylaxis received. Disease burden in preventively treated migraine patients was reported via treatment patterns, pathways, and comorbidities. HCRU was assessed through outpatient provider visits, hospitalizations, and sick leave.Results160,164 adult migraine patients were identified, of which 55,378 (34.6%) were prescribed preventive treatment with conventional (n = 25,984, 46.9%), calcitonin gene-related peptide monoclonal antibody (CGRP mAb) (n = 613, 1.1%), or off-label therapies (n = 28,781, 52.0%). 936 (1.7%) patients received Botulinum Neurotoxin Type A (BoNTA). CGRP mAb-treated patients had a high rate of triptan prescriptions (2018: 95.5%; 2019: 88.9%), migraine-related hospitalizations (2018: 33.0%; 2019: 21.0%), and sick leave (2018: 26.8%; 2019: 22.5%). A high proportion of CGRP mAb- and BoNTA-treated patients was diagnosed with abdominal and pelvic pain (34.3% and 36.2%) and low back pain (34.1% and 35.3%). These patients also showed a high prevalence of depressive episodes (49.1% and 50.1%) and chronic pain disorders (37.5% and 32.9%).LimitationsThis study focused on descriptive analyses which do not allow for assessment of causality when comparing treatment groups.ConclusionsDisease burden was high in patients receiving CGRP mAbs suggesting that patients treated preventively with CGRP mAbs shortly after product launch in Germany were severely affected, chronic migraine patients. The same may be true for patients receiving BoNTA who also showed an increased disease burden.

Real-world Adherence to Subsequent Prophylactic Therapy Among Chronic Migraine (CM) Patients Initially Treated With a Calcitonin Gene–related Peptide Monoclonal Antibody (CGRP mAb) (P6-12.009)

<h3>Objective:</h3> To examine adherence to branded preventive chronic migraine (CM) treatments among patients who initiated calcitonin gene–related peptide monoclonal antibody (CGRP mAb) treatment and subsequently added on or switched to another branded preventive treatment. <h3>Background:</h3> OnabotulinumtoxinA (OnabotA) and CGRP mAbs treat CM prophylactically. CM patients treated with a CGRP mAb may introduce a subsequent treatment, but little is known about adherence to the subsequent CM treatment. <h3>Design/Methods:</h3> This retrospective cohort study included adult CM patients (ICD-10-CM G43.7XX) treated with a CGRP mAb and a subsequent CM treatment from IBM MarketScan® claims databases (05/17/2018 – 06/30/2021). The index date was the first claim date of subsequent treatment. Patients were categorized into three cohorts: switch to another CGRP mAb, switch to OnabotA, and add-on OnabotA (concomitant with CGRP mAb ≥28 days immediately following index). Baseline characteristics were assessed during the 6-month pre-index period. Adherence was defined as ≥80% of days covered on index treatment over the 6-month follow-up period. Difference in adherence between cohorts was compared using a Chi-square test and adjusted for baseline characteristics using logistic regression. <h3>Results:</h3> A total of 1315 patients were included; 745 switched to a CGRP mAb, 449 switched to OnabotA, and 121 added OnabotA. Mean age was 41.9, 39.8, and 41.3 years, respectively, and all cohorts were ≥86% female. Adherence was highest for add-on OnabotA, followed by switch to OnabotA, and, lastly, switch to CGRP mAb (68.6% vs 61.5% vs 33.2%, respectively; <i>P</i>&lt;0.0001). After adjustment, switch to OnabotA and add-on OnabotA cohorts had 3.3 (95% CI: 2.5–4.2) and 4.6 (95% CI: 3.0–7.0) times higher odds of adherence compared with the switch to CGRP mAb cohort. <h3>Conclusions:</h3> Following a CGRP mAb, adding on or switching to OnabotA as a subsequent CM treatment was associated with significantly higher adherence over 6 months compared with switching to another CGRP mAb. <b>Disclosure:</b> Ms. Gusovsky has nothing to disclose. Ms. DONG has received personal compensation for serving as an employee of AbbVie. Ms. DONG has stock in AbbVie. Ms. DONG has received research support from National Institutes of Health. Changgeng Zhao has received personal compensation for serving as an employee of AbbVie. Changgeng Zhao has stock in AbbVie. Mr. Park has received personal compensation for serving as an employee of AbbVie. Mr. Park has stock in AbbVie. Ms. Shah has received personal compensation for serving as an employee of AbbVie. Ms. Shah has stock in AbbVie Inc. An immediate family member of Ms. Shah has received research support from National Institutes of Health.

Real-world Adherence to Subsequent CGRP mAb Treatment Among Chronic Migraine (CM) Patients Initially Treated with OnabotulinumtoxinA: A Retrospective Claims Analysis (P10-12.004)

<h3>Objective:</h3> To examine adherence to calcitonin gene–related peptide monoclonal antibody (CGRP mAb) treatment among patients who initiated onabotulinumtoxinA (OnabotA) and subsequently added on or switched to a CGRP mAb. <h3>Background:</h3> The 2021 American Headache Society consensus statement and emerging clinical reports suggest that the combination of a CGRP mAb and OnabotA in patients with migraine is probably effective. However, real-world utilization of combination treatments relative to monotherapies among patients with chronic migraine (CM) has not been examined previously. <h3>Design/Methods:</h3> In this retrospective cohort study, adult patients with CM (ICD-10-CM G43.7X) treated with OnabotA and subsequently with a CGRP mAb were identified from IBM MarketScan® claims databases (05/17/2018 – 06/30/2021). The index date was the first CGRP mAb prescription. Patients were categorized into two cohorts: “addition” (concomitant OnabotA and index CGRP mAb usage ≥28 days) and “switch” (otherwise). Adherence (≥80% of days covered on medication) over a 6-month follow-up period was assessed using logistic regression to adjust for baseline characteristics during the 6-month pre-index period. <h3>Results:</h3> The study sample included 610 patients in the addition cohort and 680 in the switch cohort. Lower adherence to index CGRP mAb was observed in the addition versus switch cohorts (38.9% vs 48.2%; <i>P</i>&lt;0.001). After controlling for baseline characteristics, the switch cohort had 41% (95% CI: 1.12–1.77; <i>P</i>=0.003) higher odds of adherence versus the addition cohort. In the addition cohort, 60.2% (n=367) of patients were adherent to OnabotA alone or in combination with a CGRP mAb, and 19.3% (n=118) were adherent to combination use of the index CGRP mAb and OnabotA. <h3>Conclusions:</h3> During follow-up, patients who added a CGRP mAb to OnabotA had significantly lower adherence to the CGRP mAb versus patients who switched to a CGRP mAb. These findings suggest that usage of CGRP mAb as add-on to OnabotA occurs for a limited duration. <b>Disclosure:</b> Ms. DONG has received personal compensation for serving as an employee of AbbVie. Ms. DONG has stock in AbbVie. Ms. DONG has received research support from National Institutes of Health. Ms. Gusovsky has nothing to disclose. Ms. Shah has received personal compensation for serving as an employee of AbbVie. Ms. Shah has stock in AbbVie Inc. An immediate family member of Ms. Shah has received research support from National Institutes of Health. Mr. Park has received personal compensation for serving as an employee of AbbVie. Mr. Park has stock in AbbVie. Changgeng Zhao has received personal compensation for serving as an employee of AbbVie. Changgeng Zhao has stock in AbbVie.

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..

Safety and Efficacy of Concomitant Erenumab and INP104 Use From the Phase 3 STOP 301 Study in Migraine Patients (P13-12.002)

<h3>Objective:</h3> To report safety and efficacy in migraine patients who concomitantly used erenumab and INP104 over 24 weeks. <h3>Background:</h3> Breakthrough migraine attacks can occur while a patient is on preventive therapy; therefore, effective acute medications that can be used concomitantly without an increased risk of adverse events (AEs) are needed. INP104 is a combination of dihydroergotamine mesylate (DHE) and Precision Olfactory Delivery approved for the acute treatment of migraine. <h3>Design/Methods:</h3> This was a post hoc analysis of the Phase 3, open-label study (STOP 301) that assessed the safety, tolerability, and exploratory efficacy of INP104 in migraine. Patients used their best usual care during a 28-day screening period. Eligible patients were provided INP104 to nasally self-administer (1.45 mg) with self-recognized attacks over 24 weeks. Concomitant preventive migraine medications were permitted if stable and not contraindicated with DHE. Erenumab was the only approved calcitonin gene-related peptide monoclonal antibody at study initiation. <h3>Results:</h3> Over 24 weeks, 8 patients concomitantly used erenumab and INP104; 5 reported no AEs. Most AEs were mild or moderate in severity. One patient reported severe AEs, which included bronchitis and serious AEs of pulmonary embolism and visual disturbance; none was treatment related. One mild case of abnormal olfactory test in another patient was possibly treatment related. At baseline, 2-hour pain and most bothersome symptom (MBS) freedom was self-reported by 22.0% and 51.5% of patients on their best usual care, respectively. At months 1, 2, 3, 4, 5, and 6, 32.3% and 54.3%, 37.1% and 70.8%, 33.3% and 50.0%, 40.3% and 68.1%, 28.0% and 42.7%, and 26.7% and 33.3% self-reported 2-hour pain and MBS freedom post-INP104, respectively. <h3>Conclusions:</h3> Results suggest that INP104 may be an effective and well-tolerated acute therapy for migraine patients who concomitantly use erenumab as a preventive therapy, with sustained benefits over 6 months. <b>Disclosure:</b> Dr. Ahmed has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Dr. Ahmed has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Dr. Vann has received personal compensation for serving as an employee of Impel Neuropharma. Dr. Vann has received personal compensation for serving as an employee of Biogen. Dr. Fitzpatrick has received personal compensation for serving as an employee of Impel Pharmaceuticals. Dr. Ray has received personal compensation for serving as an employee of Impel Pharmaceuticals. Dr. Ray has stock in Impel Pharmaceuticals. Dr. Shrewsbury has received personal compensation for serving as an employee of Impel NeuroPharma. Dr. Shrewsbury has received stock or an ownership interest from Impel NeuroPharma. Dr. Aurora has received personal compensation for serving as an employee of Impel Neuropharma. Dr. Aurora has stock in Impel Neurpharma.