Our study found a 48.9% increase in the migraine population during the measured four-year period. As other studies have found, patients treated for migraine attacks skew younger and the population averaged younger as the years progressed.

Despite the fact that the mainstays of migraine therapy show some improvement in migraine outcomes, it is reported that only 25% of patients remain on their medications at six months, and at 12 months, only 14% of patients continue to take preventative medications [30]. Medication persistence is associated with decreased migraine attacks; thus, it is imperative that patients adhere to their medication regimen. The availability of CGRP mABs makes effective preventative medication therapy a realistic option. Our data reflects this reality, showing a statistically significant increase during the four-year period.

Although the newer medications (CGRP mABs, ditans, and gepants) increased during the study period, they still represented only 17.8% of migraine prescriptions in 2020. However, because of their significantly greater cost, they accounted for 39.7% of overall costs in 2020. Due to their recent entry into the market, data are limited on comparative effectiveness of the CGRP mABs and older preventative therapies, but some conclude that CGRP mABs have similar effectiveness for migraine prophylaxis [31]. The PCORI evidence review map on migraine prophylaxis concluded similar efficacy between older preventative therapies and the CGRP mABs, but noted that evidence for older agents was compromised by higher risk of bias, due to poor randomization, unclear blinding procedures, and high attrition rates [25]. They also concluded that the CGRP mABs offered significantly greater tolerability. Thus, the popularity of the mABs likely reflects a combination of pharmaceutical marketing, favorable side effect profile compared to some of the older agents, clinical efficacy, and the convenience of monthly administration. Likewise, the newer acute migraine medications (gepants and ditans) are similar in efficacy to the triptans, but for some patients offer an alternative where the triptans are ineffective, not tolerated, or contraindicated.

Even with a slight decline in utilization over time, triptans were the most popular migraine treatment, reflecting their wide availability of products and formulations and proven track record for effectiveness. This likely reflects favorable insurance formulary practices, as most oral triptans have a generic equivalent with average wholesale prices from $9-$600 for a 30-day supply, and an average cost of $31.92 for our population in 2020 [32]. In addition, our study documents significant uptake of CGRP mABs during this period, with three CGRP mABs approved by the Federal and Drug Administration for treatment starting in 2018 [33]. The fact that utilization of other older, prophylactic medications also increased suggests the possibility that some patients were required to take these medications (and fail) prior to getting a CGRP through a prior authorization process [34] or these patients had comorbidities that warranted the continued use of these medications.

Other trends merit some discussion. Opioids are not recommended for treatment of migraine, although they are commonly used for this indication [35]. Because our data do not include indication for opioid, we cannot be certain that the opioids were used for migraine treatment. This is consistent with most studies, as indications for medications are rarely documented. Regardless, it is encouraging that use of opioids declined over the study period. It is not clear whether this reflects benefits of newer preventative therapies such as the CGRP mABs, or national trends to decrease use of opioids for all indications.

Our analysis expands upon previous research that has been conducted on migraine related costs in US based health systems, which have found the newer pharmacotherapy options are more cost-effective for a subset of patients (i.e., those who have chronic migraine attacks), especially when adding in indirect costs [36]. Prior to the approval of CGRP mABs, even with existing treatment options, it was evident that migraine attacks have high direct and indirect costs [37]. While there aren’t clear data on clinical superiority, based on the higher utilization and increased cost in our sample, it appears that some patients and physicians prefer CGRP mABs for prophylaxis. CGRP mABs, while more costly, may offer a more suitable alternative for patients unable to tolerate older prophylactic medications or due to lack of effectiveness of these agents; furthermore, many are taken once a month or once every three months, which could improve adherence [27]. These increased costs must be considered against the huge negative impact of migraines on quality of life, healthcare resource utilization [38, 39] and work outcomes [10]. Even if effectiveness of CGRP mABs is similar to older preventative therapies, the fact that they are more tolerable would be expected to have a significant impact on overall total costs of care. A recent study provides support for this contention. Irimia and colleagues found that older preventative migraine treatments were poorly tolerated with low persistence; in those patients who discontinue treatment, there were higher healthcare costs, more primary care visits, and more sick leave [40].

The study has caveats and limitations inherent with analyzing claims data. The study population mainly included commercially insured patients versus those with Medicaid and Medicare, which limits generalizability as it does not reflect national breakdowns of health insurance coverage in the US [41]. Because we did not have migraine diagnosis, we used a surrogate of migraine specific drugs to identify patients with migraine (triptans, ergotamines, isometheptene, CGRP mABs, gepants or ditans). Thus, we might miss migraine patients who only take older migraine prophylactic medications such as antidepressants. We believe that few patients would fit that scenario. Likewise, we do not know the indications for medications with multiple indications. Thus, it is possible that some of the medications attributed to migraine prophylaxis were used for another indication. Importantly, opioids may have been used for other indications. In addition, without access to patient reported data, it is difficult to examine increased and decreased utilization among certain populations, i.e., migraine prophylactic use among Medicaid enrollees. Finally, the most recent additions to acute migraine medications (gepants and ditans) have just recently entered the market and thus their presence will likely alter trends in the future.

Our study adds to the current literature as it captures the shift of utilization and cost of when CGRP mABs entered the market. These changes in utilization and cost trends allow payers and patients to have a better understanding of treatment costs, especially as clinical guidelines and practices are updated to address this expensive burden and public health problem. Future studies are needed to evaluate the impact of newer migraine medications relative to older medications on healthcare utilization, improved quality-of-life, and work outcomes for patients with migraine.