Gene-related Peptide Monoclonal Antibodies Research Articles

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.

Efficacy and Safety of Anti-CGRP Monoclonal Antibodies for Migraine Preventative Treatment (P6-12.011)

<h3>Objective:</h3> To examine the efficacy and safety of erenumab, fremanezumab, and galcanezumab, the three self-administered anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) for the treatment of high episodic and chronic migraine (CM) in the largest real-life cohort, to our knowledge. <h3>Background:</h3> Migraine is the most disabling neurological condition and can severely impact activities of daily living. There are few preventative medications with high efficacy for migraine patients. Anti-CGRP mAbs have shown promising results in terms of the severity and frequency of monthly migraine days (MMD), since its first FDA-approval in 2018. Examining real-life cohorts is necessary to confirm the efficacy and tolerability of these treatments. <h3>Design/Methods:</h3> Clinical and demographic data was extracted for patients (n=3421) whom received a minimum of 6 consecutive months of a single anti-CGRP mAb between June 2018 and December 2021. The MMD at baseline and after treatment was recorded. The cohort (85.6% female, 47.2 ± 13.8 years old, 80.3% CM) was separated into response types based on the change in their migraine frequency: “Super-responders” (≥75% MMD reduction), “Non-responders” (≤25% reduction in MMD), and “Responders” (reduction between 26–74%). <h3>Results:</h3> Treatment improved migraine frequency by 48.8% on average. The MMD decreased from a baseline of 21.9 (± 8.1) to 11.3 (± 10.3) after treatment. Super-responders accounted for 32.5% (1113/3421), Responders made up 37.0% (1265/3421), and 30.5% (1043/3421) were Non-responders. No treatment-emergent adverse events were noted, however, adverse reactions occurred in 4.2% (119/3421) of patients. <h3>Conclusions:</h3> Most anti-CGRP mAb treated patients had a positive response, determined by a reduction in MMD. Adverse reactions to the anti-CGRP mAbs occurred rarely in this cohort. Thus, the efficacious and safe use of erenumab, fremanezumab, and galcanezumab is observed in this real-life retrospective study. <b>Disclosure:</b> Miss Salim has nothing to disclose. Mr. Najjar has nothing to disclose. 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. Ignacio Mata has nothing to disclose.

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.

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.

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.

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.

Preventive Treatment With Eptinezumab in Patients With a Dual Diagnosis of Chronic Migraine and Medication-Overuse Headache: Subgroup Analysis of PROMISE-2 (S47.006)

Preventive Treatment With Eptinezumab in Patients With a Dual Diagnosis of Chronic Migraine and Medication-Overuse Headache: Subgroup Analysis of PROMISE-2 (S47.006)

Early Clinical Experience With Eptinezumab From a Retrospective, Observational Study of Real-World Patient Response (P6-12.008)

<h3>Objective:</h3> To describe the patient response, including effects on disability and function, to eptinezumab in a real-world setting after 6 months of preventive migraine treatment. <h3>Background:</h3> The anti-calcitonin gene-related peptide monoclonal antibody eptinezumab is approved for the prevention of migraine in adults. Evidence from post-marketing studies is needed to better understand how eptinezumab prevents migraine in the real-world setting. <h3>Design/Methods:</h3> This retrospective chart review examined data from adults who initiated preventive treatment and received at least 2 infusions of eptinezumab (100mg or 300mg) at headache clinics between April and October 2020. Demographic information, treatment history, migraine and headache frequency, disease characteristics, and disability assessment scores (e.g., Migraine Disability Assessment [MIDAS], Headache Impact Test [HIT-6]) were collected using standardized case-report forms completed by physicians. These report forms measured patient and clinician perspectives on eptinezumab treatment response. <h3>Results:</h3> This analysis includes data from 31 patients with migraine (mean age, 50.7 years; 100% white [27/27]; 81.5% female [22/27]; 93.5% chronic migraine [29/31]) had been collected across 8 sites. Relative to baseline, 6 months of preventive treatment with eptinezumab reduced mean monthly headache days (23.5 at baseline, 16.3 at Month 6), mean monthly migraine days (17.9 at baseline, 9.1 at Month 6), and patient-reported disability (50.0% [11/22] severe at baseline per MIDAS and/or HIT-6, 36.8% [7/19] severe at Month 6). Eptinezumab treatment was also associated with reduced acute headache medication use (16.7 mean acute medication days per month in the last 3 months prior to treatment and 8.3 at Month 6). Clinicians reported that treatment was well-tolerated (96.8%) and improved disability/function (77.4%) after 6 months of use. <h3>Conclusions:</h3> Early clinical experience with eptinezumab and the magnitude of improvement is consistent with results reported in controlled clinical trials, with reductions in headache frequency and associated disability evident during the first 6 months of treatment. <b>Disclosure:</b> Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. 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. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Seema Soni-Brahmbhatt has nothing to disclose. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck.

Adherence and Persistence of Calcitonin Gene-Related Peptide Monoclonal Antibodies in Patients with Migraine: A Real-World Study (P12-12.007)

<h3>Objective:</h3> This study compared real-world adherence and persistence in adult patients with migraine initiating CGRP mAbs– galcanezumab versus fremanezumab or erenumab. <h3>Background:</h3> Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are approved for migraine prevention. However, real-world studies comparing their treatment patterns in the US are limited. <h3>Design/Methods:</h3> This retrospective cohort study utilized administrative claims data from the Merative Marketscan® Commercial and Medicare Supplemental Databases. Included patients had ≥1 claim for an approved self-injectable CGRP mAb between May 2018 and September 2021 and had continuous enrollment in medical and pharmacy benefits (12 months pre- and 12 months post-index). Index date was defined as date of first prescription fill for a CGRP mAb (index medication). Adherence and persistence were compared for 6- and 12-months post index. Adherence to index medication was assessed as proportion of days covered (PDC) and medication possession ratio (MPR). Persistence was defined as continuous therapy from index until the end of the 12-month post-index period, allowing for a maximum gap between fills of 60 days. <h3>Results:</h3> At 12-months follow-up, 26,176 patients (&gt;85% female) were grouped into galcanezumab (n=9,121), fremanezumab (n=5,003), erenumab (n=12,052) groups based on their index medication. The mean (SD) age was 43.8 (11.3), 44.4 (11.1) and 44.7 (11.2) years, respectively. Mean (SD) PDC and MPR were 0.6 (0.3) for all three groups. More patients in the galcanezumab (45.9%) group achieved PDC ≥ 0.8 followed by fremanezumab (42.8%) and erenumab (41.8%,) groups. Similarly, 46.4%, 43.4%, 42.4% achieved MPR ≥ 0.8 in the respective groups. More patients in the galcanezumab group (52.2%) were persistent through the end of the study period, followed by fremanezumab (47.5%) and erenumab (47.8%) groups. Similar trends were observed for the 6-months follow-up cohort. <h3>Conclusions:</h3> Our findings suggest that patients treated with galcanezumab were more adherent and persistent followed by patients treated with fremanezumab and erenumab. <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. Dr. Brady has received personal compensation for serving as an employee of Merative. Anthony J Zagar has received personal compensation for serving as an employee of Eli Lilly. Miss Robles 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.. 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..

Responder Rates With Eptinezumab Over 24 Weeks in Patients With Prior Migraine Preventive Treatment Failures (S47.007)

Responder Rates With Eptinezumab Over 24 Weeks in Patients With Prior Migraine Preventive Treatment Failures (S47.007)

What trade-offs are patients willing to make when selecting between novel preventive treatments for migraine? Evidence from a Discrete Choice Experiment (P7-12.001)

<h3>Objective:</h3> To quantify the trade-offs people with episodic migraine (EM) are willing to make between the attributes of calcitonin gene-related peptide monoclonal antibodies and gepants for the prevention of migraine. <h3>Background:</h3> The introduction of new treatments for migraine prevention, such as CGRP-mAbs injectables and lately oral gepants, means that current and future treatment options differ in administration mode, efficacy, and the adverse event profile. Understanding patients’ treatment preferences can help improve how needs of patients with migraine are addressed. <h3>Design/Methods:</h3> An online discrete choice experiment (DCE) among people with self-reported EM diagnosis in the US elicited treatment preferences based on: a) treatment administration; b) chance of ≥50% reduction in monthly migraine headache days; c) onset time; d) impact of migraines on daily activities; and e) reduction in the number of days with acute medication use. Relative attribute importance (RAI) scores and maximum acceptable attribute trade-offs were obtained from a mixed logit model. <h3>Results:</h3> A total of 301 patients, mean age (standard deviation) of 45 (13) years completed the DCE. Patients were mostly female (63%), and mostly experienced with migraine preventive treatments (70%). The chance of achieving ≥50% response was the largest driver of treatment preferences (RAI: 38%), followed by onset time (RAI:20%). Treatment administration was the least important attribute (RAI: 8%). Despite differences in RAI, patients were willing to trade-off all attributes when making decisions. For example, on average, patients were willing to take a self-injectable treatment instead of a novel oral for an additional 7% chance in achieving ≥50% response. <h3>Conclusions:</h3> Preferences of patients with EM are driven by a range of treatment aspects, with chance of achieving ≥50% reduction in MHD being most important to them and administration being least important to them. The findings suggest that a patient-centric treatment strategy jointly considers and weighs all treatment aspects. <b>Disclosure:</b> Dr. Whichello has received personal compensation for serving as an employee of Evidera. Antje Tockhorn-Heidenreich has received personal compensation for serving as an employee of Eli Lilly and Company. An immediate family member of Antje Tockhorn-Heidenreich has received personal compensation for serving as an employee of Evidera. Antje Tockhorn-Heidenreich has received stock or an ownership interest from Eli Lilly and Company . An immediate family member of Antje Tockhorn-Heidenreich has received stock or an ownership interest from PPD. Dr. Quaife has received personal compensation for serving as an employee of Evidera. Ms. Trapali has received personal compensation for serving as an employee of Evidera. Tommi Tervonen has received personal compensation for serving as an employee of Evidera. Lars Viktrup has received personal compensation for serving as an employee of Lilly. Lars Viktrup has received stock or an ownership interest from Lilly. Dr. Naegeli has received personal compensation for serving as an employee of Eli Lilly and Company. Dr. Naegeli has stock in Eli Lilly and Company.

468 Use of calcitonin gene-related peptide monoclonal antibodies in patients with rosacea: An exploratory, comparative case series

468 Use of calcitonin gene-related peptide monoclonal antibodies in patients with rosacea: An exploratory, comparative case series

Medications affecting the insulin-like growth factor 1/growth hormone axis, including teprotumumab, somatostatin analogs, and anti-calcitonin gene-related peptide monoclonal antibodies, are associated with elevated reporting odds of alopecia in women: A pharmacovigilance study

Medications affecting the insulin-like growth factor 1/growth hormone axis, including teprotumumab, somatostatin analogs, and anti-calcitonin gene-related peptide monoclonal antibodies, are associated with elevated reporting odds of alopecia in women: A pharmacovigilance study

Migraine: from pathophysiology to treatment

Migraine is an extremely disabling, common neurological disorder characterized by a complex neurobiology, involving a series of central and peripheral nervous system areas and networks. A growing increase in the understanding of migraine pathophysiology in recent years has facilitated translation of that knowledge into novel treatments, which are currently becoming available to patients in many parts of the world and are substantially changing the clinical approach to the disease. In the first part of this review, we will provide an up to date overview of migraine pathophysiology by analyzing the anatomy and function of the main regions involved in the disease, focusing on how these give rise to the plethora of symptoms characterizing the attacks and overall disease. The second part of the paper will discuss the novel therapeutic agents that have emerged for the treatment of migraine, including molecules targeting calcitonin gene-related peptide (gepants and monoclonal antibodies), serotonin 5-HT1F receptor agonists (ditans) and non-invasive neuromodulation, as well as providing a brief overview of new evidence for classic migraine treatments.

Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: A retrospective cohort study.

A pharmacological class effect was initially proposed for monoclonal antibodies against the calcitonin gene related peptide pathway. However, preliminary evidence shows that switching patients who were non-responding to one monoclonal antibody to another could provide some benefit. Herein, we assess treatment response to an anti-calcitonin gene related peptide/receptor monoclonal antibody in patients who have failed to respond to anti-calcitonin gene related peptide/ligand monoclonal antibodies calcitonin gene related peptide/ligand monoclonal antibodies and vice versa. In addition, we select non-responders to the first anti- monoclonal antibody by three or five more stringent variables. Retrospective cohort study including outpatients treated consecutively with two anti-calcitonin gene related peptide monoclonal antibodies. Ineffectiveness to the first monoclonal antibody was assessed using three (MIDAS score, monthly headache days, and analgesic monthly days) variables or five (monthly headache days, MIDAS score, analgesic monthly days, analgesic monthly number and HIT-6 score) variables in the same cohort of patients. The primary endpoints were the absolute change from baseline in monthly headache days, response rate, and persistence in medication overuse at three months of treatment with the second anti-CGRP mAb. In patients selected by three variables, a sustained reduction in monthly headache days, analgesic monthly days, MIDAS and HIT-6 scores was observed at month-3 of treatment with the second monoclonal antibody. Ten (45.4%) patients achieved at least a ≥30% response rate. No difference was reported switching anti-CGRP mAb against ligand or receptor. In the patient subgroup selected by five variables, only HIT-6 was reduced from baseline at month-3. However, a trend toward a reduction in monthly headache days, analgesic monthly days, and MIDAS score was observed at month-3. Switching anti-calcitonin gene related peptide monoclonal antibodies in selected patients might be an option to achieve or improve clinical benefit. More studies are required to establish the effectiveness of switching these treatments.

Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study

BackgroundAnti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data.MethodsWe analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients’ basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences.ResultsIn total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine.ConclusionsPatients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.

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.

Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis.

Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

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.