Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Evaluation of the concomitant use of prophylactic treatments in patients with migraine under anti-calcitonin gene-related peptide therapies: The PREVENAC study.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.

RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.