Adding eptinezumab to brief patient education to treat chronic migraine and medication-overuse headache: Protocol for RESOLUTION-A phase 4, multinational, randomized, double-blind, placebo-controlled study.

Introduction: Migraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised. Brief Educational Intervention (BEI) has been shown to be an effective tool with promising results for MOH. Here, we report the design of a clinical trial that aims to evaluate the efficacy of eptinezumab, an anti-calcitonin gene-related peptide preventive migraine treatment, as an add-on to BEI for treatment of MOH in those with chronic migraine. Methods and analysis: RESOLUTION will be a phase 4, multi-national, randomized, double-blind, placebo-controlled study. This study will enroll approximately 570 participants with dual diagnoses of chronic migraine and MOH. Eligible patients will be randomly allocated to one of two treatment groups, BEI and eptinezumab (100 mg; n = 285) or BEI and placebo (n = 285), in a 1:1 ratio. The primary endpoint is the change from baseline in monthly migraine days over weeks 1-4. Secondary and exploratory endpoints will assess monthly migraine days over weeks 1-12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population. Ethics and dissemination: This study will be conducted in accordance with good clinical practice. All patients will be fully informed about the study, including the risks and benefits of participation, and all participants will provide informed consent for participation in the trial and dissemination of results.

[Non-pharmacological treatment of migraine and tension-type headache].

Migraine and tension-type headache are among the most frequent diseases of the world. As pharmacological treatment often is associated with distinct side effects, there is an increasing need for non-pharmacological treatment options. However, there has been a striking lack of evidence with regards to the efficacy of the huge variety of non-pharmacological interventions. In this review, we present the available evidence for the most common non-pharmacological treatment options with focus on the national clinical guideline for non-pharmacological treatment of headache disorders published in 2021.

Manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education in migraine treatment. A systematic review and meta-analysis.

BACKGROUND: Many people suffering from migraine combine pharmacological and non-pharmacological treatments. The purpose of this systematic review is to provide an updated guideline for some widely used non-pharmacological treatment options for migraine. METHODS: We conducted a systematic literature review of randomized studies of adults with migraine treated with manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education. The main outcomes measured were days with headache and quality of life. Recommendations were formulated based on the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) approach including patient preferences based on expert opinion and questionnaire data. RESULTS: The overall level of certainty of the evidence was low to very low. Manual therapy techniques and psychological treatment did not change the studied outcomes. Supervised physical activity might have a positive impact on quality of life, acupuncture on headache frequency, intensity, quality of life and the use of attack-medicine. Patient education might improve self-rated health and quality of life and increase the number of well-informed patients. CONCLUSION: Based on observed effects, the lack of serious adverse events, and patients' preferences, we make weak recommendations for considering the investigated interventions as a supplement to standard treatment.Protocol registration: Prospero CRD42020220132.

Treatment of medication overuse headache: Effect and predictors after 1 year-A randomized controlled trial.

BACKGROUND: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking. OBJECTIVE: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year. METHODS: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year. RESULTS: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported. CONCLUSIONS: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.

Dependence-like behaviour in patients treated for medication overuse headache: A prospective open-label randomized controlled trial.

BACKGROUND: Dependence-like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence-like behaviour is unknown. OBJECTIVES: To compare patient-reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to 6 months. METHODS: Patients with MOH were randomized to (1) withdrawal combined with preventive medication from start (W+P), (2) preventive medication without withdrawal (P), or (3) withdrawal with optional preventive medication 2 months after withdrawal (W). At baseline, 2, and 6 months, patients filled out SDS (used for measurements of dependence-like behaviour and treatment feasibility), Headache Under-Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires. RESULTS: Out of 120 patients with MOH, 100 completed the 6-month follow-up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After 6 months, the SDS score was reduced by 3.69 (95% CI 3.23-4.49) in the W+P arm, by 3.19 (95% CI 2.43-3.96) in the W arm, and by 1.65 (95% CI 0.96-2.33) in the P arm (p = 0.04). At baseline and after 2 months, the P arm was considered the most feasible treatment, but at 6-month follow-up, there was no difference in feasibility score, change in HURT score, or quality of life. CONCLUSIONS: Dependence-like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH. SIGNIFICANCE: Withdrawal combined with preventive medication from start is the treatment strategy that reduces dependence-like behaviour the most in MOH patients. Patients initially considered preventive treatment without withdrawal as the most feasible treatment. However, no difference in feasibility between the three arms was found at 6-month follow-up. Withdrawal combined with preventive medication is recommended for treatment of MOH.