Optimizing Migraine Prevention (OptMig project)

The aim of the project is to reduce the public health problem of migraines by giving more people access to good preventive migraine treatment. According to the Global Burden of Disease study, migraine is the most disabling disease in people under 50 years of age. Patients have a lot of pain and suffering, and many also a significant absence from work and school. Attack medication helps only partially, and frequent use can lead to more headaches (medication overdose headache). Many more people should therefore use preventive migraine medications, but unfortunetaly many of the medications that are available today are not ideal, owing to side effects and because they should be avoided in common conditions such as asthma, diabetes, obesity and depression. The OptMig project consists of 3 work packages to promote good preventive migraine treatment in Norway. The OptMig study as a whole seeks not only to help individual patients, but to help reduce the public health problem of migraines. Work package 1: The blood pressure medicine candesartan has been tested in our research group as preventive migraine medicine in 2 smaller pilot studies in Norway, and has shown good effect. It has few side effects and few restrictions in use. For the medicine to be accepted as a first choice, however, a large trial is needed. The CandMig3 study is a clinical trial assessing if candesartan can prevent attacks in people with frequent migraine. Patients from all over Norway and one hospital in Estonia can participate in the study. We collaborate with 9 hospitals in Norway (Tromsø, Bodø, Trondheim, Molde, Bergen, Akershus, Rikshospitalet, Ullevål, and Kristiansand) and 1 hospital in Tartu, Estonia. The last participant in the CandMig3 study was included in November 2023, and the results will be analyzed and published by the end of 2024. Work package 2: A sub-goal of the Opt-Mig project is to get more migraine patients to use preventive treatment. During the project period, we will monitor the proportion of migraine patients who use preventive treatment. We will take as our starting point the so-called NorMig study, conducted by researchers at the University of Bergen, who through the prescription register have mapped the use of such medicines in the period 2010-2020. Registry-based data shows that the use of migraine preventive medicines have been increasing during this period, but that it is still much lower than what is recommended. It is interesting that candesartan seems to come out best in terms of effect and how many people choose to continue with the medicine after 3 months and one year. A recently published paper from the research group ion Bergen showed that some established and cheaper medicines can have a similar treatment effect as the more expensive migraine preventive medicines (Bjørk MH, Comparative retention and effectiveness of migraine preventive treatments: A nationwide registry-based cohort study. Eur J Neurol. 2023 Sep 27). This may be of great significance both for the patient group and Norwegian health care. New clinical trials are being planned based on these results. Work package 3: If a migraine preventive effect of candesartan is confirmed, we will work for the state to reimburse the costs of the medicine so that candesartan becomes available to many more. Through a health economic analysis, we will investigate whether society's expenses for the medicine will be offset by the use of less attack medicines, and that hospital admissions and absenteeism will decrease.The study will also be used for an information campaign aimed at the patient group and the general public about the importance of preventive migraine treatment. We collaborate with the two user representatives in the study, who also represent the patient organization Hodepine Norge.

The Project is divided into three work packages (WPs). WP 1 is a large randomized, controlled, blinded, parallell study (RCT) on candesartan to prove efficacy, monitor side effects and find the optimal dose. Approximately 460 patients with frequent migraine attacks will be randomized to either candesartan 8mg, 16 mg, 24 mg or placebo for 12 weeks after a 4 week baseline period. The main efficacy variable is days with migraine per 4 weeks. Reduction in use of acute medication and in loss of working capacity is also measured. The study builds on two previous smaller studies showing effect. WP 2 is a prescription database study of the coverage of migraine prophylactics in Norway in the years 2017 to 2023. It will build on a previous study of the years 2009-2016. It will also measure change in use of prescribed acute medication (triptans and opioids) following institution of prophylactic medicine in patients. WP 3 is a health economic analysis of candesartan as migraine prophylactic, based on the three RCTs (present and two earlier) and the register database study, including data on change in acute medication use and in work absence and efficiency. This will be coupled with patient-driven information campaigns and policymaking to achieve that more patients use prophylactics and that the state will reimburse the cost of candesartan for migraine.