Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. METHODS: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing \u3e 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. RESULTS: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P \u3c 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P \u3c 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). CONCLUSIONS: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting

Real-World Effectiveness of Add-Onfremanezumab in Patients Receiving OnabotulinumtoxinA for the Prevention of Chronic Migraine in a US Tertiary Headache Center: A Retrospective Chart Review Study

Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population (N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased by 3.60 days (95% confidence interval [CI]: −5.26, −1.94, p \u3c 0.001) and PI was reduced by 0.43 (95% CI: −0.77, −0.09, p = 0.012) at the final visit. Statistically significant reductions were seen in both MHD (−4.61, 95% CI: −6.84, −2.39; p \u3c 0.001) and PI (−0.52, 95% CI: −0.84. −0.09; p = 0.017) among patients naïve to mAbs against CGRP or its receptor. No unexpected adverse events were observed. Conclusion: Concomitant fremanezumab and onabotA for CM prevention were effective at reducing the number of MHD and lessening PI, particularly in patients with difficult-to-treat CM who are naïve to mAbs against CGRP or its receptor

Efficacy and safety of fremanezumab in clinical trial participants aged ≥60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM). Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and FOCUS study in participants with EM or CM and prior inadequate response to 2-4 migraine preventive medication classes. Participants in all studies were randomized 1:1:1 to receive 12 weeks of subcutaneous treatment with quarterly fremanezumab (Months 1/2/3: EM/CM, 675 mg/placebo/placebo), monthly fremanezumab (Months 1/2/3: EM, 225 mg/225 mg/225 mg; CM, 675 mg/225 mg/225 mg), or matched monthly placebo. Results: These pooled analyses included 246 participants aged ≥60 years. Reductions in monthly migraine days from baseline over 12 weeks were significantly greater with fremanezumab (least-squares mean change from baseline [standard error]: quarterly fremanezumab, - 4.3 [0.59]; monthly fremanezumab, - 4.6 [0.54]) versus placebo (placebo, - 2.3 [0.57]; both P \u3c 0.01 vs placebo). As early as Week 1, significant reductions from baseline in weekly migraine days were observed with fremanezumab versus placebo (both P \u3c 0.01). With fremanezumab treatment versus placebo, a significantly higher proportion of participants achieved ≥50% reduction in monthly migraine days, and significant improvements in disability and quality-of-life outcomes were observed (P \u3c 0.05). Proportions of participants experiencing serious adverse events and adverse events leading to discontinuation were low and similar in the fremanezumab and placebo groups. Efficacy and safety results were comparable to the overall pooled population (N = 2843). Conclusions: This pooled subgroup analysis demonstrates that fremanezumab treatment is efficacious and well-tolerated over 12 weeks in participants aged ≥60 years with EM or CM. These data may help healthcare providers with clinical decision making and preventive treatment selection for older patients with migraine. Trial registration: ClinicalTrials.gov identifiers: HALO CM: NCT02621931 ; HALO EM: NCT02629861 ; FOCUS: NCT03308968

Real-world effectiveness of add-on fremanezumab in patients receiving onabotulinumtoxinA for the prevention of chronic migraine in a US tertiary headache center: A retrospective chart review study

Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population ( N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased by 3.60 days (95% confidence interval [CI]: −5.26, −1.94, p < 0.001) and PI was reduced by 0.43 (95% CI: −0.77, −0.09, p = 0.012) at the final visit. Statistically significant reductions were seen in both MHD (−4.61, 95% CI: −6.84, −2.39; p < 0.001) and PI (−0.52, 95% CI: −0.84. −0.09; p = 0.017) among patients naïve to mAbs against CGRP or its receptor. No unexpected adverse events were observed. Conclusion: Concomitant fremanezumab and onabotA for CM prevention were effective at reducing the number of MHD and lessening PI, particularly in patients with difficult-to-treat CM who are naïve to mAbs against CGRP or its receptor

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response

Abstract Introduction Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Methods Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. Results In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex. Conclusions Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response

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