Patient Sample
A total of 74,533 patients met the study eligibility criteria. Of these patients, 29,919 had no evidence of PMM use in the baseline period and were classified as PMM naïve. The remaining 44,614 patients were classified as PMM experienced, as they had PMM prescription claims and a migraine diagnosis within 90 days of the first fill in the baseline period. Among the PMM experienced patients, 26,279 (58.9%) used only one class of PMM during the baseline period, and 18,335 (41.1%) used two or more PMM classes.
The sample was primarily composed of females of middle age with commercial insurance. PMM experienced patients were slightly older and more likely to be female compared to PMM naïve patients (p <0.001; Table 1). Patients in the PMM experienced cohort also had a higher comorbidity burden than PMM naïve patients as (evidenced by a higher mean Deyo Charlson Comorbidity Index (DCI)); a significantly increased proportion of PMM experienced patients exhibited diagnoses for multiple comorbidities including anxiety and depression compared to the PMM naïve cohort (Table 1). Further, the PMM experienced cohort was significantly more likely than the PMM naïve cohort to evidence a migraine or chronic migraine diagnosis during the baseline period (p <0.001, Table 1). Among PMM experienced patients, those with two PMM classes during baseline were slightly older (p <0.001) and had a significantly higher comorbid burden than those with one PMM class.
Treatment Patterns
PMM Utilization
During the baseline period, among PMM experienced patients, 58.9% used only one PMM class, 30.0% used two PMM classes, and 11.1% used three or more classes of PMM (Table 2). Anticonvulsants were the most commonly used class of PMM at index in both the naïve and experienced cohorts; other commonly used classes included beta-blockers, tricyclics, and SNRIs. The same pattern of results was observed whether experienced patients used one or more than one PMM class during the baseline period. A significantly larger proportion of the PMM experienced cohort used each of the PMM medication classes at index compared to the PMM naïve cohort, except for anticonvulsants, which were utilized by a significantly larger proportion of the PMM naïve cohort (p <0.001, Table 2). PMM experienced patients were also more likely to exhibit use of multiple PMMs at index (poly-therapy) compared to PMM naïve patients (12% v. 2%).
Overall adherence to index PMMs was low, with a mean ± SD PDC of 0.43 ± 0.34; further, only 24% of the population was adherent (PDC ≥80%) to the index PMM over the 12-month follow up period (data not shown in Table). Consistent with the low rates of adherence, rates of discontinuation were high. The majority (71.4%) of the sample discontinued their PMM; mean ± SD time to discontinuation was 162.0 ± 142.2 days (Table 2). Discontinuation occurred rapidly, with approximately 40% of the sample discontinuing their PMM by one month post-index; a subsequent steady decline in persistence was also observed over the remainder of the follow up period (Figure 1). Rates of adherence and discontinuation were similar between the PMM experienced and naïve cohorts. Adherence and persistence rates were also similar among experienced patients with one or more than one PMM class during the baseline period.
Patterns of PMM use over the post-period were examined in the populations of experienced and naïve patients. The majority (74.4%) of the PMM naïve population used a single PMM, the index medication, during follow up (Figure 2a). Most of these naïve patients would go on to discontinue the index PMM before the end of the 12-month post period. A small proportion of patients who discontinued later re-initiated the index PMM during the follow up period (Figure 2a). Treatment patterns among patients using a single PMM over follow up were similar between the PMM naïve and experienced samples. Conversely, PMM experienced patients were significantly more likely than PMM naïve patients to use multiple PMMs over the follow up period (76.0% vs. 25.6%; Figure 2a). The majority of experienced patients who utilized multiple PMMs over follow up discontinued their index PMM and switched to a new PMM; discontinuation rates did not differ by the number of PMMs used during the baseline period. A small proportion of patients who discontinued their index PMM re-initiated treatment later in the follow up period. Approximately 30% of PMM experienced patients augmented therapy with a second PMM (poly-therapy) while continuing to take their index PMM (Figure 2). Additionally, experienced patients with two or more PMMs during the baseline period were more likely than those with only one PMM during baseline to add a new PMM class after the index date (86.4% vs. 68.8%). Rates of poly-therapy use were significantly lower in the PMM naïve subgroup who used more than one PMM, with only about 20% of naïve patients switching to a poly-therapy regimen. The remaining 80% of patients switched to a new PMM during the follow up period (Figure 2a).
Among the PMM experienced patients, the majority added at least one additional PMM during the follow-up period, and a significantly higher proportion of those already using two or more PMMs versus those using only one PMM during baseline added another PMM during follow-up (86.4% vs. 68.8%, p<0.001; Figure 2b). Regardless of the addition of a new PMM post-index, approximately 70% of PMM experienced patients discontinued the index PMM, and discontinuation rates were similar among those with one baseline PMM and those with two or more baseline PMMs. Rates of re-initiation of the index PMM were low (under 25%) and were similar among those with one versus two or more baseline PMMs.
Acute Migraine Medication Use
Utilization of acute migraine medications was common over the follow up period (Table 2). Triptans were the most commonly used acute agents within both the experienced (66.7%) and naïve (71.0%) cohorts, although among experienced patients with two or more PMMs during the baseline period, opioids were the most commonly used acute medication (66.9%). Overall, other commonly used agents included opioids (naïve: 45.6%, experienced: 59.8%), NSAIDs (naïve: 27.3%, experienced: 33.0%), and muscle relaxants (naïve: 22.8%, experienced: 34.5%). A significantly larger proportion of PMM experienced patients used all classes of acute migraine medications, with the exception of triptans, which were used by a significantly larger proportion of the PMM naïve population; the same pattern of results was observed when comparing experienced patients with more than two PMMs to those with only one PMM during baseline (Table 2). Acute migraine medication use temporarily decreased over the 30 days following index PMM discontinuation for all acute medication classes in both the experienced and naïve cohorts. The greatest declines were observed in triptans, barbiturates, opioids, and other analgesic medications. Rates of acute migraine medication use returned to baseline levels in the 90 days following index PMM discontinuation, potentially indicating a non-abatement or resurgence in migraine symptoms following PMM discontinuation.
Healthcare Costs and Service Utilization
Trends observed for all-cause and migraine-specific service use were similar (Table 3a, 3b). The PMM experienced cohort had a greater proportion of patients with inpatient (12.7% versus 7.5%) or emergency room visits (36.6% versus 29.2%) compared to the PMM naïve cohort, and among PMM experienced patients, those with two or more PMMs during baseline had a higher rate of hospitalization (16.3%) than did those with only one PMM (10.2%) during baseline (Table 3a, 3b). A similar pattern of results was observed for emergency room visits. Although the proportions of the PMM naïve and experienced cohorts with a physician office visit were similar, the PMM experienced patients had a greater number of mean physician office visits (11.8 versus 8.9), indicating increased utilization. The PMM experienced patients were also more likely to see a neurologist compared to PMM naïve patients (47.2% versus 35.9%). Utilization of brain imaging procedures was similar between the cohorts (experienced: 20.5%, naïve: 17.9%) (Table 3a, 3b).
Patients in the PMM experienced cohort had higher all-cause and migraine-specific healthcare costs and service utilization during the follow up period compared to PMM naïve patients; costs were higher for patients with two or more PMMs during the baseline period as compared to those with one PMM during baseline (Table 3a, 3b). Total all-cause healthcare costs were approximately 1.5-fold higher for the PMM experienced cohort ($19,093 versus $12,044). Within the PMM experienced cohort, costs were also 1.5 times higher for those with 2 or more PMMs ($23,702) versus those with only one PMM ($15,877) during baseline. Despite PMM experienced patients evidencing increased healthcare costs, proportional trends in costs were similar between experienced and naïve patients. Pharmacy costs accounted for approximately one-quarter of total healthcare costs, while medical costs accounted for the remaining three-quarters of total healthcare costs. Outpatient services had the greatest contribution to all-cause medical costs, accounting for more than one-half of all medical costs. Emergency room costs had the smallest contribution to medical costs.
There was also an approximate 1.6-fold difference in migraine-specific healthcare costs between the PMM experienced and naïve cohorts, with the PMM experienced patients having higher costs over the follow up period. Among the experienced cohort, migraine-specific costs were 2.3 times higher in patients with two or more PMMs ($3,992) compared to those of patients with only one PMM ($2,766) during the baseline period (Table 3b). Again, proportional trends costs were largely similar between the naïve and experienced cohorts for migraine specific costs. Outpatient services again accounted for the majority of migraine-specific medical costs. Inpatient costs had the smallest contribution to migraine specific medical costs, although, PMM experienced members had increased inpatient costs compared to PMM naïve members.
Average costs for individual healthcare encounters were also described in the full sample of both experienced and naïve patients. Although the mean ± SD costs associated with an inpatient admission ($12,050 ± $10,133) or emergency room visit ($1,003 ± $1,028) far exceeded that of office ($124 ± $68) and neurologist visits ($135 ± $76), these latter services were more often utilized, leading to them accounting for a larger proportion of all-cause and migraine-specific healthcare costs.