Abstract
Introduction
To date, no study has compared the healthcare resource utilization (HCRU), costs, and discontinuation of the two calcitonin gene-related peptide antagonists, galcanezumab (monoclonal antibody subcutaneously injected monthly) and rimegepant (oral gepant taken every other day), for migraine prevention. This study aimed to assess all-cause and migraine-related HCRU, costs, and treatment discontinuation at 12 months following treatment initiation in commercial/Medicare beneficiaries with episodic migraine who received galcanezumab versus rimegepant as preventive migraine treatment.
Methods
This retrospective study used the Merative™ MarketScan® Research Databases (June 2020–June 2023). Adults with episodic migraine were grouped into the galcanezumab (≥ 1 claim) or rimegepant cohort (≥ 1 claim with quantity ≥ 15 during the index period). Changes from baseline in all-cause and migraine-related HCRU and cost between the propensity score-matched cohorts were determined using Wilcoxon signed rank test and chi-square test. Treatment discontinuation was assessed using Kaplan–Meier analysis and Cox proportional hazards model.
Results
All-cause and migraine-related HCRU and costs increased over the 12-month follow-up in both cohorts. The galcanezumab cohort had a significantly lower increase in mean all-cause total medical + pharmacy costs (21% lower) and migraine-related total medical + pharmacy costs (76% lower) than the rimegepant cohort at the 12-month follow-up (p < 0.0001 for both assessments). Mean (standard deviation) number of days from initiation to discontinuation (> 60-day gap) was 244.6 (135.3) for galcanezumab cohort and 178.1 (141.1) for rimegepant cohort (p < 0.0001). Treatment discontinuation rate was 1.8 times less likely in the galcanezumab cohort than the rimegepant cohort (hazard ratio = 1.81, 95% confidence interval = 1.56–2.10). Similar trends were observed using a 30-day gap.
Conclusion
Among matched patients, both cohorts of patients with episodic migraine showed all-cause and migraine-related total cost increases over 12 months. However, the magnitude of the increases was significantly lower for the galcanezumab cohort than for the rimegepant cohort. Treatment discontinuation rate was significantly lower in the galcanezumab versus the rimegepant cohort.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12325-024-03072-9.
Keywords: CGRP mAbs, Costs, Discontinuation, Galcanezumab, Healthcare resource utilization, Migraine prevention, Rimegepant
Key Summary Points
| Why carry out this study? |
| Galcanezumab is a once-monthly, injectable preventive treatment for patients with migraine, and rimegepant is an oral medication taken every other day and indicated for preventive treatment of episodic migraine in adult patients. |
| There are no real-world studies comparing the calcitonin gene-related peptide antagonists, galcanezumab and rimegepant, in healthcare resource utilization (HCRU), costs, and discontinuation rate. |
| Using a United States administrative claims data, we aimed to assess healthcare resource utilization, costs, and discontinuation rate over 12 months after treatment initiation in patients with episodic migraine who initiated galcanezumab versus rimegepant for migraine prevention. |
| What was learned from the study? |
| While total HCRU and costs increased in both cohorts over 12 months, the mean increase in total cost (for all-cause and migraine-related, respectively) was lower in the galcanezumab than in the rimegepant cohort. Discontinuation rates were also lower for the galcanezumab than the rimegepant cohort. |
| Findings from this real-world study support the use of galcanezumab as preventive treatment for migraine and can help guide healthcare practitioners and payers to choose appropriate preventive medications for persistent migraine management. |
Introduction
Migraine is a common, complex, and debilitating neurological disorder characterized by episodes of moderate-to-severe headache [1, 2], with an estimated global prevalence of 14–15% [3]. It affects approximately 40 million people in the United States (US), and the prevalence of migraine has remained stable from 2005 to 2018 in the US [4–7]. The symptoms of migraine can last for hours to days and interfere with daily activities, work, and social interactions [8]. Globally, migraine accounts for 4.9% of disease burden quantified in years lived with disability [3].
The economic burden of migraine in the US is significant, encompassing both direct medical costs and indirect costs related to lost productivity and disability [5, 9, 10]. A study estimating the migraine hospital burden trend in the US over 15 years reported that the nationwide inpatient hospital charges increased from US$176 million in 1997 to $1.2 billion in 2012 [5]. The annual cost associated with migraine was estimated at $36 billion in 2016 [11]. A 2018 real-world study reported that patients with migraine have total annual direct plus indirect costs that are $8924 (in 2014 USD) higher than those of individuals without migraine [9]. These trends and estimates suggest that effective and timely management of migraine is imperative to improve outcomes and reduce the burden of migraine.
Preventive therapy is recommended in patients with migraine for ≥ 2 days per month when there is acute medication overuse and/or when quality of life is moderately to severely impaired. Some of the traditional preventive medications for migraine were not developed specifically for migraine and some of them are associated with severe adverse effects and risk of medication overuse [12, 13]. Evidence supporting the efficacy, tolerability, and safety of calcitonin gene-related peptide (CGRP) antagonists for migraine prevention is now substantial, as highlighted in the American Headache Society updated consensus statement recommending the drug class as first-line therapy for migraine prevention [14].
Galcanezumab [US Food and Drug Administration (FDA) approved 2018], is a once-monthly, injectable preventive treatment for patients with episodic or chronic migraine [15]. Rimegepant (FDA approved 2021) is an oral medication indicated for both acute treatment of migraine and preventive therapy for episodic migraine in adults [16]. However, rimegepant is not indicated for the preventive treatment of chronic migraine. Dosing for rimegepant is need-based for acute migraine treatment (maximum of 18 doses) and every other day for preventive migraine treatment.
The efficacy of CGRP antagonists were assessed in a meta-analysis of 19 phase III randomized–controlled clinical studies showing all reduced mean monthly migraine days compared to placebo, with rimegepant reducing them by 0.8 days and galcanezumab by 2.3 days [17]. A single double-dummy, 3-month, head-to-head clinical study enrolling mostly preventive migraine treatment–naive participants, galcanezumab did not demonstrate superiority over rimegepant for achieving a ≥ 50% reduction from baseline in migraine headache days per month; however, both interventions demonstrated efficacy as preventive treatments in participants with episodic migraine [18]. The efficacy and safety profile observed in participants treated with galcanezumab was consistent with previous studies of episodic migraine [19].
Previous studies have examined healthcare resource utilization (HCRU) and costs associated with injectable CGRP monoclonal antibodies (mAbs) [20, 21], but no real-world studies have compared healthcare utilization and costs of injectable CGRP antagonists and oral CGRP antagonists. Understanding the difference in real-world costs and treatment utilization patterns between galcanezumab and rimegepant will add value to existing data.
The aim of this study was to assess all-cause and migraine-related HCRU, costs, and discontinuation rate at 12 months following treatment initiation who received galcanezumab versus rimegepant for migraine prevention among patients with episodic migraine.
Methods
Study Design and Data Source
This was a retrospective, observational, claims-based study, which used data from the Merative™ MarketScan® Commercial and Medicare Databases. Access to the data was granted through an internal agreement with Eli Lilly and Company and Merative. These databases contain data for several million individuals (employees) and their spouses and dependents who are covered by employer-sponsored private health insurance in the US. All database records are de-identified and fully compliant with US patient confidentiality requirements, including the Health Insurance Portability and Accountability Act of 1996.
The index date was defined by the first date of galcanezumab or rimegepant claim between June 1, 2021, and June 30, 2022. The 12 months prior to the index date comprised the baseline period and the 12 months after the index date comprised the follow-up period (Fig. 1). Patients were assigned to one of two cohorts based on the migraine treatment initiated on the index date: galcanezumab or rimegepant cohort.
Fig. 1.
Study design
Institutional review board approval to conduct this study was not required, as the study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data.
Study Population
Patients were included if they were ≥ 18 years old on the index date and had ≥ 1 claim for galcanezumab 120 mg or rimegepant 75 mg between June 1, 2021, and June 30, 2022 (for rimegepant, only claims with a quantity of ≥ 15 were counted, as rimegepant is recommended for administration every other day for preventive use). Patients were continuously enrolled in medical and pharmacy benefits in the 12 months before and after the index date (baseline and follow-up periods) and had ≥ 1 medical claim with an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis code for episodic migraine during the baseline period or on the index date.
Patients were excluded from the study if there was evidence of cluster headache diagnosis, pregnancy, cancer, and epilepsy diagnosis during the study period. For the galcanezumab cohort, patients with any claims for other CGRP mAbs (erenumab, fremanezumab, eptinezumab) and gepants indicated for prevention (rimegepant quantity of ≥ 15 and atogepant) during the baseline period or on the index date were excluded. For the rimegepant cohort, patients with any claims for CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) and atogepant during the baseline period or on the index date were excluded.
Outcomes and Variables
Demographics measured on the index date included age, sex, geographical region of residence, insurance type, and type of provider. Provider type was determined based on the closest medical claim in the 45 days prior to and including the index claim. Charlson Comorbidity Index, a weighted composite score to measure mortality risk based on 19 comorbid conditions, was obtained during the 12-month baseline period. Comorbid medical conditions were identified by the presence of ≥ 1 inpatient or any position on non-diagnostic outpatient medical claim with an ICD-10-CM diagnosis code during the 12-month baseline period. Acute and preventive medications, identified by the presence of ≥ 1 outpatient prescription claim or medical claim with a procedure code for the administration of the medications, were reported during the 12-month baseline period. Acute medication included: antiemetics, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), barbiturate (butalbital), ergotamine, isometheptene, opioids, triptans, lasmiditan, ubrogepant, and rimegepant (quantity of ≤ 8 or “1 pack”). Preventive medications included anticonvulsants, tricyclic antidepressants, beta-blockers, angiotensin receptor blockers, calcium channel blockers, botulinum toxin A, CGRP mAbs, and gepants.
Measures of all-cause and migraine-related HCRU during the 12-month baseline and follow-up periods included: number of inpatient admissions, emergency room visits, outpatient office visits, other outpatient services, and outpatient pharmacy claims. Migraine-related HCRU and costs were calculated based on the presence of a migraine diagnosis on the claim line (in the primary position on inpatient claims and any position on outpatient claims) and migraine treatments, while all-cause HCRU and direct costs were calculated based on all claims in all sites of care.
Discontinuation of index medication was defined as failure to refill the index medication within 60 days after the depletion of the days’ supply from previous fills. The date of discontinuation was defined as the date of run out of days’ supply of the last prescription filled prior to the first observed gap in therapy. Sensitivity analysis using a 30-day gap was also reported.
Statistical Analysis
Categorical variables were presented as the count and percentage of patients in each category. Continuous variables were summarized by the mean, standard deviations (SDs), and medians. Paired t-test and McNemar test were used to compare the HCRU and costs between the baseline and follow-up periods. As cost data were skewed, both mean and median were reported. Cox proportional hazards regression analyses were conducted to estimate the hazard ratio of discontinuation for the galcanezumab and rimegepant cohorts. Kaplan–Meier survival curves were used to show the probability of discontinuation of each treatment.
Greedy propensity score matching (1:1, with a caliper of 0.02, standardized distance on the propensity score scale between 0 and 1) was used to minimize baseline differences between patients initiating galcanezumab and rimegepant cohorts. Cohorts were matched on the following 34 covariates: age, sex, region, provider type, and the baseline characteristics including back pain, coronavirus disease 2019, chronic pain, gastroesophageal reflux disease [GERD], headache, hyperlipidemia, nausea, obesity, stroke, anxiety, asthma, depression, diabetes, fibromyalgia, osteoarthritis, sleep disorder, any preventive migraine medication use, beta blocker use, anti-epileptic use, tricyclic antidepressant use, any acute migraine medication use, CGRP/gepant use, triptan use, anti-emetic use, NSAID use, opioid use, ubrogepant use, rimegepant use (≤ quantity of 8), all-cause total medical + pharmacy costs, and migraine-related total medical + pharmacy costs. Patient factors are shown in Table 1 as covariates in the model to generate the propensity score based on previous studies and clinical relevance.
Table 1.
Patient demographics, clinical characteristics, migraine medication utilization, and total healthcare costs before and after matching during the 12-month baseline period
| Before matching | After matching | |||||
|---|---|---|---|---|---|---|
| Galcanezumab (n = 880) | Rimegepant (n = 1128) | Std diffa | Galcanezumab (n = 602) |
Rimegepant (n = 602) | Std diffa | |
| Age, mean (SD) | 43.7 (11.2) | 42.7 (11.3) | 9% | 43.4 (11.0) | 43.8 (11.0) | 4% |
| Female, n (%) | 783 (89.0) | 986 (87.4) | 5% | 531 (88.2) | 539 (89.5) | 4% |
| Insurance type: commercial, n (%) | 866 (98.4) | 1123 (99.6) | 12% | 592 (98.3) | 601 (99.8) | 16% |
| Provider type, n (%) | ||||||
| Otherb | 428 (48.6) | 431 (38.2) | 21% | 277 (46.0) | 281 (46.7) | 1% |
| PCP | 217 (24.7) | 416 (36.9) | 27% | 166 (27.6) | 167 (27.7) | – |
| Neurologist | 106 (12.1) | 190 (16.8) | 13% | 85 (14.1) | 85 (14.1) | – |
| Missing | 129 (14.7) | 91 (8.1) | 21% | 74 (12.3) | 69 (11.5) | 2% |
| Deyo–Charlson Comorbidity index, mean (SD) | 0.4 (0.9) | 0.3 (0.8) | 12% | 0.4 (0.8) | 0.4 (0.8) | – |
| Selected comorbid medical conditions, n (%) | ||||||
| Anxiety | 391 (44.4) | 438 (38.8) | 11% | 257 (42.7) | 248 (41.2) | 3% |
| Asthma | 126 (14.3) | 131 (11.6) | 8% | 75 (12.5) | 80 (13.3) |
2 % |
| Back Pain | 390 (44.3) | 409 (36.3) | 16% | 247 (41.0) | 247 (41.0) | - |
| COVID | 119 (13.5) | 166 (14.7) | 3% | 79 (13.1) | 89 (14.8) | 5% |
| Depression | 239 (27.2) | 251 (22.3) | 11% | 149 (24.8) | 156 (25.9) | 3% |
| Diabetes | 87 (9.9%) | 89 (7.9) | 7% | 53 (8.8) | 57 (9.5) | 2% |
| Fibromyalgia | 56 (6.4) | 58 (5.1) | 6% | 31 (5.2) | 38 (6.3) | 5% |
| Headache | 234 (26.6) | 305 (27.0) | 1% | 158 (26.3) | 162 (26.9) | 1% |
| Hyperlipidemia | 226 (25.7) | 264 (23.4) | 5% | 151 (25.1) | 158 (26.3) | 3% |
| Sleep Disorder | 225 (25.6) | 213 (18.9) | 16% | 129 (21.4) | 134 (22.3) | 2% |
| GERD | 196 (22.3) | 203 (18.0) | 11% | 123 (20.4) | 119 (19.8) | 1% |
| Nausea | 121 (13.8) | 133 (11.8) | 6% | 73 (12.1) | 76 (12.6) | 2% |
| Obesity | 166 (18.9) | 191 (16.9) | 5% | 110 (18.3) | 111 (18.4) | 0% |
| Osteoarthritis | 123 (14.0) | 119 (10.6) | 10% | 77 (12.8) | 80 (13.3) | 1% |
| Sleep disorder | 225 (25.6) | 213 (18.9) | 16% | 129 (21.4) | 134 (22.3) | 2% |
| Stroke | 48 (5.5) | 51 (4.5) | 5% | 30 (5.0) | 33 (5.5) | 2% |
| Chronic Pain | 124 (14.1) | 120 (10.6) | 11% | 73 (12.1) | 78 (13.0) | 3% |
| Any preventive migraine medication, n (%) | 521 (59.2) | 566 (50.2) | 31% | 330 (54.8) | 343 (57.0) | 4% |
| Anti-epileptics | 265 (30.1) | 284 (25.2) | 22% | 169 (28.1) | 176 (29.2) | 2% |
| Beta-blockers | 228 (25.9) | 222 (19.7) | 30% | 126 (20.9) | 139 (23.1) | 5% |
| Tricyclic antidepressants | 171 (19.4) | 175 (15.5) | 24% | 108 (17.9) | 117 (19.4) | 4% |
| CCBs | 36 (4.1) | 28 (2.5) | 40% | 23 (3.8) | 15 (2.5) | 7% |
| ARB | 4 (0.5) | 2 (0.2) | 61% | 4 (0.7) | 2 (0.3) | 6% |
| Botox | 14 (1.6) | 21 (1.9) | − 17% | 8 (1.3) | 14 (2.3) | 8% |
| Any acute migraine medication, n (%) | 856 (97.3) | 1009 (89.5) | 76% | 578 (96.0) | 583 (96.8) | 4% |
| Triptans | 509 (57.8) | 540 (47.9) | 33% | 336 (55.8) | 338 (56.2) | 1% |
| NSAIDs | 478 (54.3) | 531 (47.1) | 25% | 307 (51.0) | 311 (51.7) | 1% |
| CGRP gepants | 403 (45.8) | 312 (27.7) | 55% | 226 (37.5) | 215 (35.7) | 4% |
| Antiemetics | 369 (41.9) | 384 (34.0) | 29% | 232 (38.5) | 244 (40.5) | 4% |
| Opioids | 338 (38.4) | 367 (32.5) | 23% | 222 (36.9) | 213 (35.4) | 3% |
| Ubrogepant | 119 (13.5) | 69 (6.1) | 58% | 53 (8.8) | 55 (9.1) | 1% |
| Butalbital | 104 (11.8) | 137 (12.2) | -3% | 64 (10.6) | 80 (13.3) | 8% |
| Rimegepant quantity ≤ 8 | 494 (56.1) | 273 (24.2) | 75% | 254 (42.2) | 249 (41.4) | 2% |
| Total all-cause costs, $ | 23,042 (32,112) | 15,087 (24,101) | 29% | 17,948 (18,353) | 18,651 (29,071) | 3% |
| Total migraine-related costs, $ | 3,414 (4,849) | 2,765 (4,385) | 14% | 3,064 (4,659) | 2,999 (3,785) | 2% |
ARB angiotensin receptor blocker, CCB calcium channel blocker, CGRP calcitonin gene-related peptide, GERD gastroesophageal reflux disease, NSAID nonsteroidal anti-inflammatory drug, PCP primary care provider, SD standard deviation, std diff standardized difference
aCovariates with a standardized difference (std diff; expressed in percentage) ≥ 10% are in bold, suggesting a potential imbalance between cohorts. The 1:1 ratio propensity score-matched galcanezumab and rimegepant cohorts were well balanced
bOther refers to any provider type that is non-PCP and non-neurologist
We assessed the balance of baseline characteristics between the cohorts using standardized differences (std diff), quantifying the difference in means between the two cohorts relative to their pooled SD. A std diff greater than 10% is considered indicative of an imbalance between cohorts in observational studies [22]. This threshold was applied to identify covariates that needed adjustment reducing potential bias. A significance level of 0.05 was specified a priori as the threshold for statistical significance for any statistical comparisons across groups.
Results
Patient Sample and Baseline Characteristics
A total of 880 and 1128 patients had initiated galcanezumab and rimegepant, respectively, as the index drug (Fig. 2). Before propensity score matching, galcanezumab initiators compared to rimegepant initiators had a lower percentage of primary care physicians as the provider type (24.7% vs. 36.9%, std diff = 0.27), higher Deyo–Charlson Comorbidity Index (0.4 vs. 0.3, std diff = 0.12), and a higher rate of the following comorbidities: anxiety (44.4% vs. 38.8%, std diff = 0.11), back pain (44.3% vs. 36.3%, std diff = 0.16), depression (27.2% vs. 22.3%, std diff = 0.11), sleep disorder (25.6% vs. 18.9%, std diff = 0.16), GERD (22.3% vs. 18.0%, std diff = 0.11), and chronic pain (14.1% vs. 10.6%, std diff = 0.11; Table 1). Furthermore, unmatched patients in the galcanezumab cohort had higher baseline use of any preventive migraine medication (59.2% vs. 50.2%, std diff = 0.31) and any acute migraine medication (97.3% vs. 89.5%, std diff = 0.76) than those in the rimegepant cohort. During the baseline period, unmatched galcanezumab initiators had higher all-cause total costs ($23,042 vs. $15,087, std diff = 0.29) and migraine-related total costs ($3414 vs. $2,765, std diff = 0.14) than unmatched rimegepant initiators (Table 1).
Fig. 2.
Patient flowchart. For rimegepant, only claims with a quantity of ≥ 15 were counted, as rimegepant is recommended for administration every other day for preventive use. CGRP mAbs calcitonin gene-related peptide monoclonal antibodies, HCPCS Healthcare Common Procedure Coding System, NDC National Drug Code
After 1:1 propensity score matching, the matched galcanezumab and rimegepant samples comprised 602 patients each and were well balanced across the 34 variables (Supplementary Fig. 1). Patients in the matched cohorts had a mean age of approximately 43.4–43.8 years and comprised mostly females (88.2–89.5%; Table 1). Nearly half of the patients resided in the south (50.2–50.8%) of the US. The top 2 comorbid medical conditions were anxiety and back pain. In both matched cohorts, the majority (~ 96%) used an acute migraine medication, and over half of the patients (54.8–57.0%) used a preventive migraine medication (Table 1). The most commonly used acute medications were triptans, NSAIDs, and antiemetics, while the most commonly used preventive medications were anti-epileptics, followed by beta-blockers and tricyclic antidepressants (Table 1).
All-Cause HCRU and Costs of the Matched Cohorts Over the 12-month Follow-up Period
During the 12-month follow-up period, the galcanezumab cohort had a statistically significant increase in the mean number of all-cause outpatient office visits [baseline vs. follow-up: 44.5 (55.3) vs. 52.2 (77.6), p = 0.0026], other outpatient services [58.7 (61.6) vs. 64.5 (72.2), p = 0.0131], and pharmacy fills [45.0 (31.5) vs. 53.4 (36.4), p < 0.0001], while the rimegepant cohort had a significant increase from baseline to follow-up in pharmacy fills [40.3 (34.9) vs. 46.5 (34.3), p < 0.0001; Table 2]. The mean change in all-cause outpatient visits was significantly higher for the galcanezumab cohort than for the rimegepant cohort (7.7 vs. – 1.7, p = 0.0036).
Table 2.
All-cause HCRU in matched patients initiating galcanezumab versus rimegepant over 12 months
| Galcanezumab | Rimegepant | Galcanezumab vs. Rimegepant p value (mean change from baseline to follow-up) |
|||||
|---|---|---|---|---|---|---|---|
| Baseline (n = 602) |
Follow-up (n = 602) |
p value (baseline vs. follow-up) | Baseline (n = 602) |
Follow-up (n = 602) |
p value (baseline vs. follow-up) | ||
| Inpatient admissions | |||||||
| Mean (SD) | 2.5 (16.2) | 2.0 (10.0) | 0.5169 | 2.2 (12.6) | 2.3 (19.1) | 0.8685 | 0.5922 |
| Median (IQR) | 0 (0–0) | 0 (0–0) | – | 0 (0–0) | 0 (0–0) | – | – |
| ER visits | |||||||
| Mean (SD) | 1.8 (4.5) | 1.9 (4.6) | 0.7726 | 2.4 (6.2) | 2.1 (6.3) | 0.3188 | 0.3517 |
| Median (IQR) | 0 (0–1.8) | 0 (0–1) | – | 0 (0–3.0) | 0 (0–0) | – | – |
| Outpatient office visits | |||||||
| Mean (SD) | 44.5 (55.3) | 52.2* (77.6) | 0.0026 | 46.1 (63.9) | 44.4* (53.6) | 0.3892 | 0.0036 |
| Median (IQR) | 26.0 (13.0–58.0) | 29.0 (15.0–61.0) | – | 27.0 (12.3–50.8) | 26.0 (13.0–53.0) | – | – |
| Other outpatient servicesa | |||||||
| Mean (SD) | 58.7 (61.6) | 64.5* (72.2) | 0.0131 | 53.8 (54.8) | 55.4* (45.2) | 0.2488 | 0.1229 |
| Median (IQR) | 42.0 (27.0–70.0) | 48.0 (32.0–79.8) | – | 35.0 (22.3–67.0) | 42.0 (27.0–72.0) | – | – |
| Pharmacy fills | |||||||
| Mean (SD) | 45.0** (31.5) | 53.4** (36.4) | < 0.0001 |
40.3** (34.9) |
46.5* (34.3) | < 0.0001 | 0.0515 |
| Median (IQR) | 37.0 (23.0–59.0) | 44.0 (28.3–67.0) | – | 30.0 (18.0–51.8) | 36.5 (24.0–60.8) | – | – |
Mean number of each HCRU is captured among those with ≥ 1 corresponding utilization category
ER emergency room, HCRU healthcare resource utilization, IQR interquartile range, SD standard deviation
aOther outpatient HCRU includes home health care, pharmacy administration and outpatient services, skilled nursing facility, telehealth, and surgical center location
p values in bold indicate statistical significance
*p value < 0.05 in the follow-up utilization between galcanezumab and rimegepant
**p value < 0.05 in the baseline utilization between galcanezumab and rimegepant
All-cause total (medical + pharmacy) costs increased over the 12-month follow-up period in both the galcanezumab and rimegepant cohorts (Fig. 3). The galcanezumab cohort had increase in mean and median total medical cost (mean difference: $2371; median change from $4765 to $5016) while the rimegepant cohort had a decrease in mean total medical costs and an increase in median total medical costs (mean difference: – $281; median change from $4466 to $4610). Compared to the rimegepant cohort, the galcanezumab cohort had a 21% lower mean change in all-cause total medical + pharmacy costs ($8378 vs. $10,641, p < 0.0001).
Fig. 3.
All-cause cost changes for matched patients initiating galcanezumab versus rimegepant over 12 months. (a) All-cause total medical cost change for matched patients initiating galcanezumab versus rimegepant over 12 months. (b) All-cause total medical and pharmacy cost change for matched patients initiating galcanezumab versus rimegepant over 12 months
Migraine-related HCRU and Costs in the Matched Cohorts Over the 12-month Follow-up Period
During the 12-month follow-up period, there was a statistically significant increase in the mean number of migraine-related pharmacy fills in both cohorts [baseline vs. follow-up: galcanezumab, 12.2 (10.8) vs. 13.5 (11.6), p < 0.0001; rimegepant, 12.4 (11.0) vs. 16.2 (12.3), p < 0.0001; Table 3]. The mean change in the number of migraine-related pharmacy fills was significantly lower for the galcanezumab cohort than for the rimegepant cohort (1.3 vs. 3.8, p < 0.0001).
Table 3.
Migraine-related HCRU in matched patients initiating galcanezumab versus rimegepant over 12 months
| Galcanezumab | Rimegepant | Galcanezumab vs. Rimegepant p value (mean change from baseline to follow-up) |
|||||
|---|---|---|---|---|---|---|---|
| Baseline (n = 602) |
Follow-up (n = 602) |
p value (baseline vs. follow-up) | Baseline (n = 602) |
Follow-up (n = 602) |
p value (baseline vs. follow-up) | ||
| Inpatient admissions | |||||||
| Mean (SD) | 0.0 (0.6) | 0.1 (1.5) | 0.4117 | 0.0 (1.0) | 0 (0) | 0.3177 | 0.2206 |
| Median (IQR) | 0 (0–0) | 0 (0–0) | – | 0 (0–0) | 0 (0–0) | – | – |
| ER visits | |||||||
| Mean (SD) | 0.3 (1.4) | 0.2 (1.2) | 0.4804 | 0.3 (1.3) | 0.3 (2.0) | 0.8087 | 0.7868 |
| Median (IQR) | 0 (0–0) | 0 (0–0) | – | 0 (0–0) | 0 (0–0) | – | – |
| Outpatient office visits | |||||||
| Mean (SD) | 5.8 (13.0) | 6.0 (12.8) | 0.8833 | 5.0 (9.8) | 4.8 (12.0) | 0.7134 | 0.7275 |
| Median (IQR) | 2.0 (1.0–5.0) | 3.0 (1.0–5) | – | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | – | – |
| Other outpatient servicesa | |||||||
| Mean (SD) | 0.5* (1.9) | 0.4 (1.3) | 0.2787 | 0.3* (0.8) | 0.3 (1.2) | 0.8172 | 0.3116 |
| Median (IQR) | 0 (0–0) | 0 (0–0) | – | 0 (0–0) | 0 (0–0) | – | – |
| Migraine-related pharmacy fills | |||||||
| Mean (SD) | 12.2 (10.8) | 13.5** (11.6) | < 0.0001 | 12.4 (11.0) | 16.2** (12.3) | < 0.0001 | < 0.0001 |
| Median (IQR) | 9.0 (5.0–17.0) | 11.0 (5.0–18.0) | – | 9.5 (5.0–16.0) | 14.0 (8.0–21.0) | – | – |
The mean number of each HCRU is captured among those with ≥ 1 corresponding utilization category
HCRU healthcare resource utilization, IQR interquartile range, SD standard deviation
aOther outpatient HCRU includes home health care, pharmacy administration and outpatient services, skilled nursing facility, telehealth, and surgical center locations
p values in bold indicate statistical significance
*p value < 0.05 in the baseline utilization between galcanezumab and rimegepant
**p value < 0.05 in the follow-up utilization between galcanezumab and rimegepant
Migraine-related total (medical + pharmacy) costs increased over the 12-month follow-up period in both the galcanezumab and rimegepant cohorts (Fig. 4A). The galcanezumab cohort had a decrease in both mean and median total medical costs (mean difference: $-36; median change from $395 to $374), while the rimegepant cohort had an increase in mean total medical costs and a decrease in median total medical costs (mean difference: $33; median change from $360 to $276). The galcanezumab cohort had a 76% lower mean increase in the migraine-related total (medical + pharmacy) cost during the follow-up when compared to the rimegepant cohort ($2172 vs. $9041, p = 0.88) (Fig. 4B).
Fig. 4.
Migraine-related costs for matched patients initiating galcanezumab versus rimegepant over 12 months. (a) Migraine-related costs for matched patients initiating galcanezumab versus rimegepant over 12 months. (b) Migraine-related total medical and pharmacy cost change for matched patients initiating galcanezumab versus rimegepant over 12 months
Treatment Discontinuation in the Matched Cohorts Over the 12-month Follow-up Period
A significantly smaller proportion of patients discontinued treatment in the galcanezumab cohort than in the rimegepant cohort (49.4% vs. 69.1%, p < 0.0001). Mean (SD) time to discontinuation (60-day gap) was significantly longer in the galcanezumab cohort than in the rimegepant cohort [244.6 (135.3) vs. 178.1 (141.1) days, p < 0.0001] (Fig. 5).
Fig. 5.
Time to discontinuation (for a 60-day gap) of matched patients initiating galcanezumab and rimegepant
Treatment discontinuation results based on a 30-day gap were consistent with those based on a 60-day gap (Supplementary Fig. 2).
Discussion
This real-world, observational, claims-based study followed patients with episodic migraine for 12 months and demonstrated that total HCRU and costs increased in both galcanezumab and rimegepant cohorts. Patients initiating galcanezumab had a 21% lower mean increase in all-cause total costs and a 76% lower mean increase in migraine-related total costs compared to those initiating rimegepant. The lower cost increase with galcanezumab versus rimegepant was mainly due to significantly lower pharmacy costs in the galcanezumab cohort. Additionally, galcanezumab initiators had a significantly lower discontinuation rate than the rimegepant initiators.
The majority of patients in this study were women and had anxiety and back pain as the top 2 comorbidities. Most patients had used anti-epileptics, beta-blockers, or tricyclic antidepressants as preventive medication and triptans or NSAIDs as acute medication for migraine. These results were consistent with findings in prior real-world, treatment pattern studies in patients with migraine [21, 23–26].
There is currently a lack of studies describing HCRU in patients initiating rimegepant for migraine prevention. Our study found that the mean change in the number of migraine-related pharmacy fills, which included both acute and preventive medication (Table 3), was significantly higher for the rimegepant cohort than for the galcanezumab cohort. This may explain some of the increased costs in the rimegepant cohort. While the migraine-related outpatient office visits did not change in any of the cohorts, the all-cause outpatient office visits increased significantly more with the galcanezumab cohort than the rimegepant cohort (Table 2). Though the study analyses balanced 34 covariates in the more severe galcanezumab cohort (Table 1), it is possible an unbalanced non-migraine condition is behind this finding.
A real-world study based on data from 2018–2019 showed an increase in the mean annual all-cause total costs of $8,398 and mean annual migraine-related total costs of $4,334 in patients who initiated galcanezumab, which are consistent with cost increases observed in the current study [21]. A recent cost-effectiveness analysis from the Health Outcome Division at the University of Texas, using available literature data, reported that rimegepant cost (acquisition cost of $22,399) accounted for 79% of all-cause total healthcare costs [27].
Previous studies have demonstrated that the persistence rate for preventive migraine medication was 25% at 6 months and 14–26.2% at 12 months [28, 29]. A previous real-world study showed a discontinuation rate of 43.2% at 12 months follow-up in patients with migraine treated with galcanezumab, which is consistent with that in our study (49.4%) [24]. No other studies have shown real-world treatment patterns, including discontinuation rates, for rimegepant in the migraine prevention landscape. Despite advances in treatment efficacies, high discontinuation rates persist for migraine preventive treatment. The Spanish PERSEC study assessed electronic medical records over 1 year and identified persistent oral migraine prevention treatment translated into lower HCRU and cost [30]. Common reasons for treatment discontinuation in migraine include lack of treatment effectiveness, low tolerability, and high costs for both traditional preventive migraine treatment and newer CGRP antagonists [31–35].
Strengths and Limitations
This is the first study to compare galcanezumab and rimegepant in healthcare resource utilization, costs, and treatment discontinuation and hence address critical gaps in the literature regarding the use of these medications in the real-world setting. Discontinuation rates for galcanezumab consistent with those in previous studies add credibility to the study findings.
The study findings should be interpreted in the context of the following limitations. First, these study findings are not generalizable to those with no insurance or with insurance other than commercial health or private Medicare supplemental insurance (e.g., Medicaid). Second, despite using propensity score matching to balance baseline characteristics, there may be residual confounding due to unmeasured variables, including but not limited to clinical severity and patient preferences for treatment, which could influence outcomes and exacerbate treatment selection bias [36]. In this study, the exclusion criterion related to the use of other migraine treatments exclusively affected the galcanezumab cohort, suggesting that these patients may have unmeasured characteristics (e.g., clinical severity or time since first migraine diagnosis) that differ from those in the rimegepant cohort and not accounted for by propensity score matching. Third, the sample size was reduced during the propensity score matching due to the lack of suitable matches, which restricts the analysis to a sub-population that is not explicitly defined. Fourth, administrative claims data are subject to data coding or data entry errors by healthcare providers and claims processors that may lead to misclassification of migraines, comorbidities, or medication use. And fifth, clinical data on disease severity, progression, and patient experiences were not available for inclusion in the current study. In addition, data on co-pay and sampling of medications were not available to be considered. The cost data did not account for rebates as they were not captured in the database. Furthermore, these two drugs with different routes of administration entered the US market at different time points. Finally, treatment utilization was estimated based on the assumption that medication fills were equivalent to consumption/usage. Moreover, over-the-counter medications were not available in the database to be considered.
Conclusion
In this study of commercial and Medicare beneficiary matched samples in the US, both the galcanezumab and rimegepant cohorts showed an increase in all-cause and migraine-related total costs over 12 months, with a lower mean cost increase in patients initiating galcanezumab compared to those initiating rimegepant. Treatment discontinuation rates over 12 months were also lower in the galcanezumab cohort than in the rimegepant cohort. These findings add to the growing real-world evidence comparing the preventive treatments for migraine and provide insight regarding appropriately addressing non-compliance to preventive treatments observed in the migraine preventive treatment landscape. Future studies should consider the efficacy, safety, patient preference for the route of administration, HCRU over a longer period, and inclusion of patients with a history of CGRP to better understand factors for the difference in all-cause and migraine-related HCRU and costs among individual CGRP antagonists, and between injectable and oral CGRP-based migraine preventive treatments.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgments
Medical Writing and Editorial Assistance
We thank Keerthana Muthiah, an employee of Eli Lilly Services India Pvt. Ltd., for her medical writing and editorial support. This support was funded by Eli Lilly and Company.
Author Contributions
Gilwan Kim and Lars Viktrup contributed to the conception of the work. Gilwan Kim, Margaret Hoyt, and Lars Viktrup contributed to the design of the work. Margaret Hoyt, Armen Zakharyan, and Jennifer Durica contributed to the acquisition of data. Margaret Hoyt, Armen Zakharyan and Jennifer Durica contributed to the analysis of data. Gilwan Kim, Margaret Hoyt, Armen Zakharyan, Alexandra Wallem, and Lars Viktrup contributed to the interpretation of data. Gilwan Kim, Margaret Hoyt, Armen Zakharyan, Alexandra Wallem and Lars Viktrup contributed to the drafting of work. Gilwan Kim, Margaret Hoyt, Armen Zakharyan, Alexandra Wallem and Lars Viktrup contributed to the critical reviewing of the work for important intellectual content.
Funding
This study was funded by Eli Lilly and Company (Indianapolis, IN, USA). Eli Lilly and Company also funded the journal’s Rapid Service and Open Access Fees.
Data Availability
Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.
Declarations
Conflict of Interest
Gilwan Kim, Margaret Hoyt, Jennifer Durica, Alexandra Wallem, and Lars Viktrup are employees and minor stockholders of Eli Lilly and Company. Armen Zakharyan is an employee of TechData Service Company, LLC.
Ethical Approval
Institutional review board approval to conduct this study was not required, as the study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data provided at www.vivli.org.
References
- 1.Ruschel map, jesus od. Migraine headache [updated 2023 Aug 23]. Treasure Island (fl): Statpearls publishing; available from: https://www.ncbi.nlm.nih.gov/books/nbk560787/ (Statpearls [internet]). Accessed Jan 2024.
- 2.Puledda F, Silva EM, Suwanlaong K, Goadsby PJ. Migraine: from pathophysiology to treatment. J Neurol. 2023;270(7):3654–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Steiner TJ, Stovner LJ. Global epidemiology of migraine and its implications for public health and health policy. Nat Rev Neurol. 2023;19(2):109–17. [DOI] [PubMed] [Google Scholar]
- 4.Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: Updated statistics from government health surveillance studies. Headache. 2015;55(1):21–34. [DOI] [PubMed] [Google Scholar]
- 5.Law HZ, Chung MH, Nissan G, et al. Hospital burden of migraine in United States adults: A 15-year national inpatient sample analysis. Plast Reconstr Surg Glob Open. 2020;8(4): e2790. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343–9. [DOI] [PubMed] [Google Scholar]
- 7.Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53(3):427–36. [DOI] [PubMed] [Google Scholar]
- 8.de Begasse DO, Sakai F. Migraine in the workplace. eNeurolSci. 2022;27: 100408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bonafede M, Sapra S, Shah N, et al. Direct and indirect healthcare resource utilization and costs among migraine patients in the United States. Headache. 2018;58(5):700–14. [DOI] [PubMed] [Google Scholar]
- 10.Yucel A, Thach A, Kumar S, et al. Estimating the economic burden of migraine on us employers. Am J Manag Care. 2020;26(12):e403–8. [DOI] [PubMed] [Google Scholar]
- 11.Mrf migraine research foundation. Migraine fact sheet New York, NY: Migraine research foundation; 2016 [cited 2024]. Available from: https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed Jan 2024.
- 12.Buse DC, Sakai F, Matharu M, et al. Characterizing gaps in the preventive pharmacologic treatment of migraine: multi-country results from the CaMEO-I study. Headache. 2024;64(5):469–81. [DOI] [PubMed] [Google Scholar]
- 13.Tzankova V, Becker WJ, Chan TLH. Pharmacologic prevention of migraine. CMAJ. 2023;195(5):E187–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Charles AC, Digre KB, Goadsby PJ, et al. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American headache society position statement update. Headache. 2024;64(4):333–41. [DOI] [PubMed] [Google Scholar]
- 15.U.S. Food and Drug Administration. Emgality® (galcanezumab-gnlm) injection, for subcutaneous use. Initial U.S. Approval: 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761063s006lbl.pdf. Accessed Jul 2024.
- 16.U.S. Food and Drug Administration. Nurtec® ODT (rimegepant) orally disintegrating tablets, for sublingual or oral use. Initial U.S. Approval: 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212728s009lbl.Pdf. Accessed Jul 2024.
- 17.Haghdoost F, Puledda F, Garcia-Azorin D, et al. Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: a systematic review and network meta-analysis of phase 3 randomised controlled trials. Cephalalgia. 2023;43(4):3331024231159366. [DOI] [PubMed] [Google Scholar]
- 18.Schwedt TJ, Myers Oakes TM, Martinez JM, et al. Comparing the efficacy and safety of galcanezumab versus rimegepant for prevention of episodic migraine: results from a randomized, controlled clinical trial. Neurol Ther. 2024;13(1):85–105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Martin V, Samaan KH, Aurora S, et al. Efficacy and safety of galcanezumab for the preventive treatment of migraine: a narrative review. Adv Ther. 2020;37(5):2034–49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Varnado OJ, Gulati T, Wheeler A, Hoyt M. 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. Patient Prefer Adherence. 2023;17:3449–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Varnado OJ, Manjelievskaia J, Ye W, et al. Health care resource utilization and costs associated with treatment among patients initiating calcitonin gene-related peptide inhibitors vs. other preventive migraine treatments in the United States. J Manag Care Spec Pharm. 2022;28(8):818–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Normand ST, Landrum MB, Guadagnoli E, et al. Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores. J Clin Epidemiol. 2001;54(4):387–98. [DOI] [PubMed] [Google Scholar]
- 23.Ahmed Z, Honomichl R, Thompson SF, et al. Clinical characteristics and patient-reported outcomes of chronic and episodic migraine patients at a US tertiary headache center: a retrospective observational study. Headache. 2023;63(7):908–16. [DOI] [PubMed] [Google Scholar]
- 24.Varnado OJ, Manjelievskaia J, Ye W, et al. Treatment patterns for calcitonin gene-related peptide monoclonal antibodies including galcanezumab versus conventional preventive treatments for migraine: a retrospective US claims study. Patient Prefer Adherence. 2022;16:821–39. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Vivekanantham A, Edwin C, Pincus T, et al. The association between headache and low back pain: a systematic review. J Headache Pain. 2019;20(1):82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Zhou Z, Urman R, Gill K, et al. Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. J Headache Pain. 2023;24(1):153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Thaliffdeen R, Yu A, Rascati K. Cost-effectiveness evaluation of oral CGRP antagonists, atogepant and rimegepant, for the preventative treatment of episodic migraine: results from a us societal perspective model. Clin Drug Investig. 2024;44(3):209–17. [DOI] [PubMed] [Google Scholar]
- 28.Hepp Z, Dodick DW, Varon SF, et al. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalalgia. 2017;37(5):470–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Orlando V, Mucherino S, Monetti VM, et al. Treatment patterns and medication adherence among newly diagnosed patients with migraine: a drug utilisation study. BMJ Open. 2020;10(11): e038972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Irimia P, Garcia-Azorin D, Nunez M, et al. Persistence, use of resources and costs in patients under migraine preventive treatment: The PERSEC study. J Headache Pain. 2022;23(1):78. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Blumenfeld AM, Bloudek LM, Becker WJ, et al. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II). Headache. 2013;53(4):644–55. [DOI] [PubMed] [Google Scholar]
- 32.Mechtler L, Saikali N, McVige J, et al. 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. Front Neurol. 2021;12: 788159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Hubig LT, Smith T, Chua GN, et al. A stated preference survey to explore patient preferences for novel preventive migraine treatments. Headache. 2022;62(9):1187–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Nissan GR, Kim R, Cohen JM, et al. Reducing the burden of migraine: safety and efficacy of CGRP pathway-targeted preventive treatments. J Clin Med. 2022;11:15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Al-Hassany L, Lyons HS, Boucherie DM, et al. The sense of stopping migraine prophylaxis. J Headache Pain. 2023;24(1):9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Brooks JM, Ohsfeldt RL. Squeezing the balloon: propensity scores and unmeasured covariate balance. Health Serv Res. 2013;48(4):1487–507. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.