Calcitonin gene-related peptide-targeted monoclonal antibodies (CGRP mAbs) are increasingly being used as preventive treatments for migraine. Their effectiveness and safety were established through numerous randomized placebo-controlled trials and real-world studies, yet a significant proportion of patients do not respond to this treatment, and currently, there is a lack of accepted predictors of response to guide expectations, as data from studies so far are lacking and inconsistent. We searched Embase and MEDLINE databases for studies reporting on predictors of response to CGRP and/or CGRP-receptor (CGRP-R) mAbs, defined as a 30% or 50% reduction in monthly headache or migraine days at varying durations of follow-up. Quantitative synthesis was performed where applicable. We found 38 real-world studies that investigated the association between various predictors and response rates. Based on these studies, good response to triptans and unilateral pain with or without unilateral autonomic symptoms are predictors of a good response to CGRP(-R) mAbs. Conversely, obesity, interictal allodynia, the presence of daily headaches, a higher number of non-successful previous prophylactic medications, and psychiatric comorbidities including depression are predictive of a poor response to CGRP(-R) mAbs. Future studies should confirm these results and help to generate more tailored treatment strategies in patients with migraine.

Background and Purpose—The ankle-brachial index (ABI) is a fast, cheap, noninvasive indicator of atherosclerotic burden that may also be a predictor of stroke recurrence. In this systematic review and meta-analysis, we sought to explore ABI’s merit as a marker for stroke recurrence and vascular risk by synthesizing the data currently available in stroke literature. Methods—We searched Embase, MEDLINE, and Pubmed databases for prospective cohort studies that included consecutive patients with stroke and transient ischemic attack, measured ABI at baseline, and performed a follow-up assessment at least 12 months after initial stroke or transient ischemic attack. The following end points were chosen for our analysis: recurrent stroke and combined vascular end point (recurrent vascular event or vascular death). Crude risk ratios and adjusted Cox proportional hazard ratios were combined separately using the random-effects model. Study-level characteristics (eg, percent of cohort with a history of hypertension, average cohort age, level of adjustment, and mean follow-up duration) were included as covariates in a metaregression analysis. Results—We identified 11 studies (5374 patients) that were not significantly heterogeneous. Pooling adjusted hazard ratios showed that low ABI was associated with both an increased hazard of recurrent stroke (hazard ratio, 1.70; 95% confidence interval, 1.10–2.64) and an increased risk of vascular events or vascular death (hazard ratio, 2.22; 95% confidence interval, 1.67–2.97). Conclusion—Our results confirm the positive association between ABI and stroke recurrence. Further studies are needed to see whether inclusion of ABI will help improve the accuracy of prediction models and management of stroke patients.

Background: Monoclonal antibodies (mAbs) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway are safe and effective treatments for migraine prevention. However, the high cost of these novel therapies has led to reimbursement policies requiring patients to try multiple traditional preventives before access. In Germany, a recent change in insurance policy significantly expanded coverage for the CGRP receptor mAb erenumab, enabling migraine patients who failed just one prior prophylactic medication to receive this mAb. Here, we compare the clinical response to treatment with erenumab in migraine patients treated using the old and new coverage policy. Methods: In this retrospective cohort study, we included CGRP-mAb naïve patients with episodic or chronic migraine, who started erenumab at our headache center according to either the old or the new insurance policy and received at least 3 consecutive injections. Headache diaries and electronic documentation were used to evaluate reductions in monthly headache and migraine days (MHD and MMD) and ≥ 50% and ≥ 30% responder rates at month 3 (weeks 9–12) of treatment. Results: We included 146 patients who received erenumab according to the old policy and 63 patients that were treated using the new policy. At weeks 9–12 of treatment, 37.7% of the old policy group had a 50% or greater reduction in MHD, compared to 63.5% of the new policy group (P < 0.001). Mean reduction in MHD was 5.02 days (SD = 5.46) and 6.67 days (SD = 5.32, P = 0.045) in the old and new policy cohort, respectively. After propensity score matching, the marginal effect of the new policy on treatment outcome was 2.29 days (standard error, SE: 0.715, P = 0.001) more reduction in MHD, and 30.1% (SE: 10.6%, P = 0.005) increase in ≥ 50% response rate for MHD. Conclusions: Starting erenumab earlier in the course of migraine progression in a real-world setting may lead to a better response than starting after multiple failed prophylactic attempts. Continually gathering real-world evidence may help policymakers in deciding how readily to cover CGRP-targeted therapies in migraine prevention.

Background: Therapeutic options for migraine prevention in non-responders to monoclonal antibodies (mAbs) targeting Calcitonin Gene-Related Peptide (CGRP) and its receptor are often limited. Real-world data have shown that non-responders to the CGRP-receptor mAb erenumab may benefit from switching to a CGRP ligand mAb. However, it remains unclear whether, vice versa, erenumab is effective in non-responders to CGRP ligand mAbs. In this study, we aim to assess the efficacy of erenumab in patients who have previously failed a CGRP ligand mAb.Methods: This monocentric retrospective cohort study included patients with episodic or chronic migraine in whom a non-response (< 30% reduction of monthly headache days during month 3 of treatment compared to baseline) to the CGRP ligand mAbs galcanezumab or fremanezumab led to a switch to erenumab, and who had received at least 3 administrations of erenumab. Monthly headache days were retrieved from headache diaries to assess the ≥30% responder rates and the absolute reduction of monthly headache days at 3 and 6 months of treatment with erenumab in this cohort.Results: From May 2019 to July 2022, we identified 20 patients who completed 3 months of treatment with erenumab after non-response to a CGRP ligand mAb. Fourteen patients continued treatment for ≥6 months. The ≥30% responder rate was 35% at 3 months, and 45% at 6 months of treatment with erenumab, respectively. Monthly headache days were reduced from 18.6 ± 5.9 during baseline by 4.1 ± 3.1 days during month 3, and by 7.0 ± 4.8 days during month 6 compared to the month before treatment with erenumab (p< 0.001, respectively). Responders and non-responders to erenumab did not differ with respect to demographic or headache characteristics.Conclusion: Switching to erenumab in non-responders to a CGRP ligand mAb might be beneficial in a subgroup of resistant patients, with increasing responder rates after 6 months of treatment. Larger prospective studies should aim to predict which subgroup of patients benefit from a switch.

Introduction: Migraine is a debilitating neurological disease with a multifaceted pathophysiology. Pre‐existing comorbidities may influence the risk of developing migraine. This review and meta‐analysis aim to present a comprehensive overview of the known comorbidities predisposing individuals to new migraine onset, thereby improving our understanding of the respective diseases' interactions.Methods: A systematic search of PubMed and EMBASE identified studies on pre‐existing comorbidities as risk factors for new migraine onset. We performed three‐level meta‐analyses employing restricted maximum likelihood estimation to calculate pooled risk ratios (pRR). Subgroup and sensitivity analyses were conducted to assess the robustness of the data. Risk of bias (RoB) was assessed with the Quality in Prognostic Studies Tool. This review was pre‐registered on Prospero (CRD42024501140).Results: From a total of 17,330 records, we identified 38 studies, encompassing 124 effect sizes from 58 exposures. Most studies (n = 28, 74%) had a low RoB. Heterogeneity was high (>90%), primarily due to within‐study differences (>50%), and was not significantly impacted by moderator tests or the exclusion of outliers. We found significantly increased risks for migraine onset associated with prior atopic conditions [pRR = 1.53 (1.15, 2.03)], psychiatric or psychological disorders [pRR = 2.63 (1.79, 3.85)], sleep disorders [pRR = 1.89 (1.26, 2.85)], and cardiovascular conditions [pRR = 1.72 (1.07, 2.76)].Conclusions: Pre‐existing atopic, psychiatric, sleep, and cardiovascular conditions are significantly associated with new migraine onset, likely due to shared genetic predisposition and mediating factors like stress and inflammation. Future research should focus on these associations to advance targeted prevention and treatment strategies.

Background: Diagnosing headache disorders poses significant challenges, particularly in primary and secondary levels of care (PSLC), potentially leading to misdiagnosis and underdiagnosis. This study evaluates diagnostic agreement for migraine, tension-type headache (TTH), and cluster headache (CH) between PSLC and tertiary care (TLC) and assesses adherence to the International Classification of Headache Disorders 3rd edition (ICHD-3) guidelines. Methods: A retrospective, cross-sectional analysis was conducted at Charité - Universitätsmedizin Berlin’s tertiary headache center. The patients’ self-reported diagnoses from the PSLC were compared with those in TLC and with ICHD-3 criteria. Cohen’s kappa (κ) and R² were used to assess diagnostic agreement. Results: Among 1,468 patients (43.4 ± 14.4 years; 74.5% women), 69.5% reported a diagnosis in PSLC, and 99.5% were diagnosed at their first TLC visit. Overall agreement between PSLC and TLC was 80% (κ = 0.55; R²=30%). Agreement between the PSLC and ICHD-3 was 77% for migraine, 82% for TTH, and 96% for CH (κ = 0.65; R²=41%). TLC diagnoses aligned with ICHD-3 in over 90%. Conclusion: Our findings indicate a significant degree of diagnostic agreement across different levels of care according to the ICHD-3 guidelines. However, there remains insufficient reliability in clinical diagnostics, highlighting the need for continued efforts to improve the early recognition and diagnostic accuracy and consistency of primary headaches to optimize patient care and treatment outcomes in Germany.