Anti-CGRP Migraine Drugs Cut Monthly Headache Days by Nearly Half in Catalan Cohort

A five-year analysis of Spain’s largest public health system has found that preventive migraine drugs targeting the CGRP pathway cut monthly migraine days by roughly 45 percent among patients treated in routine practice, while their uptake grew so quickly that cumulative pharmaceutical spending exceeded 18 million euros by the end of 2023. The retrospective population-based cohort study, published in Drugs – Real World Outcomes, drew on mandatory clinical and billing registries covering the entire Catalan Health Service, a publicly funded system serving approximately eight million people, and tracked every reimbursed treatment with erenumab, fremanezumab or galcanezumab between January 2019 and December 2023.

Over the study period, 5438 adult patients received 7270 treatment episodes, and 1437 patients, or 26.4 percent, received two or more of these antibody treatments. The pace of adoption was striking: annual treatment initiations rose from just 72 in 2019 to 2406 in 2023. By the end of follow-up, 4036 treatment episodes were still ongoing and 3234 had been discontinued. Reasons for discontinuation were recorded for only 822 of the discontinued episodes, or 25.4 percent, and among those with available information, lack of effectiveness was the most frequently cited reason, followed by adverse events and patient decision.

The clinical results come from a registry-based response framework rather than a randomised trial. Treating neurologists entered baseline information at treatment initiation and recorded follow-up assessments during routine visits, with effectiveness routinely evaluated approximately three months after starting therapy and again at nine months. Complete response was defined as at least a 50 percent reduction in monthly headache days, or a 30 percent reduction combined with at least a one-category improvement on the Headache Impact Test-6 severity scale among patients whose baseline score exceeded 55, or disease remission. Partial response was defined independently as at least a 30 percent reduction in monthly headache days. Episodes stopped for drug-related reasons before assessment were counted as non-responders, while episodes without an evaluable follow-up and without documented discontinuation were excluded from the corresponding analysis.

Among the 6581 treatment episodes with complete baseline data, 5934, or 90.2 percent, had evaluable follow-up information. Response at three months was available for 4902 episodes, and 2779 remained evaluable at nine months. At three months, 48.0 percent of episodes achieved at least a 50 percent reduction in monthly migraine days, and 57.4 percent met the partial response threshold of at least 30 percent. At nine months, complete response was observed in 58.9 percent of evaluable episodes and partial response in 67.8 percent, indicating maintained benefit among patients who stayed on treatment. The authors note that attrition among non-responders may have led to some overestimation of the longer-term response rates.

Mean monthly migraine days fell from 16.68 at baseline to 10.67 at three months and to 9.09 at nine months, an overall reduction of approximately 45 percent. Because the number of evaluable episodes shrank over follow-up, the researchers also ran a longitudinal analysis restricted to the 2451 episodes with data at all three time points. In that cohort, mean monthly migraine days dropped from 16.39 at baseline to 9.43 at three months and remained essentially stable at 9.08 at nine months, a pattern the authors say supports the consistency of the observed effectiveness findings. Response rates differed by migraine subtype at three months, with complete response in 52.6 percent of patients with episodic migraine versus 43.8 percent of those with chronic migraine, a statistically significant difference, but no significant differences emerged by sex or healthcare level, and the subtype gap was no longer evident at nine months.

The patients themselves carried a heavy disease burden. Among the 5058 patients meeting treatment initiation criteria, most were female with a median age of 48 years, and baseline migraine frequency averaged 16.57 monthly migraine days with elevated HIT-6 scores. A total of 4101 patients, or 81.1 percent, had previously received more than three conventional preventive treatments, with a mean of 3.44 prior therapies. Under Catalan Health Service reimbursement rules, those conventional options included beta-blockers such as propranolol or metoprolol, topiramate, flunarizine, amitriptyline and, for chronic migraine, at least three cycles of onabotulinumtoxinA. Baseline burden in this real-world cohort exceeded that seen in randomised trials: whereas trials reported 16.2 to 19.6 migraine days per month in chronic migraine, this population averaged 22.3 days per month.

Acute medication use also fell substantially. Comparing defined daily doses dispensed in the six months before treatment with the six months after the third treatment month among 2711 patients with dispensing data in both periods, the median number of DDDs of acute migraine medications decreased by 40 percent, from 40 to 24 per six-month period, a difference the researchers report as statistically significant using the Wilcoxon signed-rank test. The most frequently dispensed acute treatments were zolmitriptan, accounting for 40 percent, rizatriptan at 21 percent and eletriptan at 13 percent. The authors suggest that reduced acute medication use may also lower the risk of medication-overuse headache in chronic migraine populations, though dispensing data served only as a proxy for actual consumption.

The economic picture changed as quickly as the clinical one. Total cumulative reimbursed expenditure on the three antibodies between 2019 and 2023 reached 18,435,240 euros, and annual spending climbed from 1.3 million euros in 2020 to 8.3 million euros in 2023. During the same period, the mean annual cost per treated patient rose 33 percent, from 1333 euros in 2020 to 1775 euros in 2023. The expenditure analysis included only reimbursed dispensations of the three antibodies, excluded acute medications and other preventive therapies, and was reported in nominal euros without adjustment for inflation, so the figures describe budget impact rather than a formal economic evaluation.

Drug choice and persistence also shifted over time. Fremanezumab became the most frequently prescribed antibody from 2020 onwards, which the authors attribute possibly to dosing flexibility and evidence in chronic migraine, while erenumab and galcanezumab continued to gain ground, suggesting that prescribing remained influenced by individual patient characteristics and response patterns. Median treatment duration across the cohort was 18.87 months, with longer persistence for fremanezumab at 24.61 months compared with 17.48 months for erenumab and 16.13 months for galcanezumab, corresponding to roughly one and a half years of persistence under routine conditions. Frequent switching and discontinuation, the authors write, highlight heterogeneity in response and the need for personalised strategies and structured follow-up for high-cost therapies.

The study has clear limits. Its retrospective, descriptive design was intended to characterise utilisation, effectiveness and expenditure rather than identify predictors of response or compare treatment strategies, and no comparative effectiveness or cost-effectiveness analysis against oral preventives or gepants was performed. Treatment adherence was not directly assessed, reasons for discontinuation were incompletely recorded, safety outcomes were not analysed, and indirect costs, broader healthcare utilisation and productivity effects were outside the scope of the analysis. Even so, the authors argue that the population-based design, which captured all reimbursed treatments across the Catalan public system, minimises selection bias and offers a comprehensive view of routine practice. They conclude that continuous monitoring of real-world effectiveness, utilisation patterns and pharmaceutical expenditure is needed to keep these high-cost therapies appropriately and sustainably deployed, and they call for future work on longer-term outcomes, adherence, safety and formal cost-effectiveness modelling.

Subject of Research: Real-world effectiveness, utilisation and pharmaceutical expenditure of anti-CGRP monoclonal antibodies for migraine prevention in the Catalan public healthcare system

Article Title: Real-World Effectiveness and Utilisation of Anti-CGRP Monoclonal Antibodies for Migraine Prevention in a Public Healthcare System

Article References: Tarrasó, G., Umbria, M., Paco, N., Vives, R., Gasol, M., & Vallano, A. (2026). Real-World Effectiveness and Utilisation of Anti-CGRP Monoclonal Antibodies for Migraine Prevention in a Public Healthcare System. Drugs – Real World Outcomes. https://doi.org/10.1007/s40801-026-00585-3

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00585-3

Keywords: migraine, CGRP monoclonal antibodies, erenumab, fremanezumab, galcanezumab, real-world evidence, migraine prevention, pharmaceutical expenditure, Catalan Health Service, treatment persistence, acute medication use, observational study