Prevalence and characteristics of rapid eye movement sleep behaviour disorder in adults with migraine: a cross-sectional screening study.

BACKGROUND AND PURPOSE: Migraine and sleep disorders share a bidirectional relationship, but little is known about the specific association between migraine and rapid eye movement (REM) sleep behaviour disorder (RBD). The aim was to assess the prevalence of RBD and associated clinical characteristics in adults with migraine. METHODS: This analysis is part of a cross-sectional survey study conducted at the Headache Centre of the Charité-Universitätsmedizin Berlin between August 2020 and March 2023. At the end of their regular medical consultation, patients with migraine filled out (1) the validated RBD Screening Questionnaire (RBDSQ), (2) a questionnaire on REM sleep intrusions and (3) the Depression, Anxiety and Stress Scale 21. The primary endpoint was the percentage of patients with a positive RBD screening. A multivariate analysis was performed to identify characteristics independently associated with features of RBD. RESULTS: A total of 751 patients (44.1 ± 13.2 years; 87.4% female) with complete RBDSQ were included in this analysis, of which 443 (58.9%) screened positive for RBD. In multivariate analysis, a positive screening for RBD was associated with younger age (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.8-0.9 per 10-year increase; p = 0.005) and with features suggestive of REM sleep intrusions (OR 4.3, 95% CI 1.8-10.4; p = 0.001). Migraine aura remained in the model without reaching statistical significance (OR 1.3, 95% CI 0.9-1.8; p = 0.079). DISCUSSION: Symptoms of RBD are frequent in adults with migraine. Further studies including polysomnography are required to confirm this association, and to explore potential common pathophysiological mechanisms.

Alice in Wonderland Syndrome (AIWS): prevalence and characteristics in adults with migraine.

OBJECTIVE: Alice in Wonderland Syndrome (AIWS) is a sensory disorder characterized by a distorted somatosensory and/or visual perception. Additionally, distortion of time perception and symptoms of derealization/depersonalization may occur. AIWS is frequently associated with migraine. However, its prevalence, and clinical characteristics remain poorly understood. Here, we investigated the prevalence and features of AIWS in individuals with migraine. We hypothesized AIWS is more frequent in migraine patients with aura than in those without aura. METHODS: This was a prospective cross-sectional cohort study, conducted at a tertiary headache center. Participants with migraine filled out questionnaires, providing details on demographics, headache, AIWS characteristics and the occurrence of transient visual phenomena such as fragmented vision. RESULTS: Of 808 migraine patients, 133 individuals (16.5%, mean age 44.4 ± 13.3 years, 87% women) reported AIWS symptoms throughout their lives. Micro- and/or telopsia (72.9%) were most frequent, followed by micro- and/or macrosomatognosia (49.6%), and macro- and/or pelopsia (38.3%), lasting on average half an hour. AIWS symptoms occurred in association with headache in 65.1% of individuals, and 53.7% had their first AIWS episode at the age of 18 years or earlier. Migraine patients with aura were more likely to report AIWS symptoms than those without aura (19.5% vs. 14.1%, p = 0.04). Participants with AIWS reported a higher incidence of 17 out of the 22 investigated visual phenomena. CONCLUSION: AIWS symptoms appear to be a common lifetime phenomenon in migraine patients. The correlation and clinical parallels between AIWS and migraine aura could indicate shared underlying pathomechanisms.

Triptan non-response in specialized headache care: cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'. METHODS: We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure. RESULTS: A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% (n = 970) had failed ≥ 1 triptan, 13.1% (n = 300) had failed ≥ 2 triptans (meeting the EHF definition of 'triptan resistance'), and 3.9% (n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency (p < 0.001), intensity (p < 0.05), and disability (p < 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan. CONCLUSION: In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Near-death experiences are associated with rapid eye movement (REM) sleep intrusions in migraine patients, independent of migraine aura.

BACKGROUND AND PURPOSE: Migraine aura, near-death experiences (NDEs), and rapid eye movement (REM) sleep intrusions might share common mechanisms. Here, we investigated the prevalence of NDEs and REM sleep intrusions in people with migraine. We hypothesized that NDEs and REM sleep intrusions are more prevalent in migraine patients with aura than in those without. METHODS: We conducted a prospective cross-sectional cohort study at a tertiary headache center, based on a prespecified sample size (n = 808). Migraine patients completed a series of questionnaires, including questions about demographic and headache characteristics, the 16-item Greyson NDE scale, four questions about REM sleep intrusions, and the Depression, Anxiety, and Stress Scale 21 (DASS-21). RESULTS: Of 808 migraine patients (mean age 44.4 ± 13.3 years, 87.0% women), 353 (43.7%) had a current or previous history of migraine aura. Prevalence of NDE was 2.7% and not different in patients with and without aura (2.8% vs. 2.6%; p > 0.999). REM sleep intrusions were reported by 5.4% of participants and in a similar proportion of patients with and without aura (6.3% vs. 4.9%; p = 0.43). However, participants with REM sleep intrusions had had an NDE more often than participants without REM sleep intrusions (n = 5/44, 11.4% vs. n = 17/754, 2.2%; p = 0.005). Higher DASS-21 scores were associated with REM sleep intrusions (p < 0.001). CONCLUSIONS: In this tertiary center cohort study, the prevalence of NDE and REM sleep intrusions was not influenced by migraine aura status. However, we identified an association between NDE and REM sleep intrusions, which corroborates the notion that they might share pathophysiological mechanisms.

Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: a subgroup analysis of the Finesse Study.

BACKGROUND: Monoclonal antibodies targeting the CGRP pathway are effective and safe for prophylactic treatment of episodic (EM) and chronic migraine (CM). In case of treatment failure of a CGRP pathway targeting mAb, physician has to decide whether using another anti-CGRP pathway mAb is useful. This interim analysis of Finesse Study evaluates effectiveness of the anti-CGRP mAb fremanezumab in patients with a history of other prior anti-CGRP pathway mAb treatments (switch patients). METHODS: FINESSE, a non-interventional, prospective, multicentre, two-country (Germany-Austria) study observing migraine patients receiving fremanezumab in clinical routine. This subgroup analysis presents data on documented effectiveness over 3 months after the first dose of fremanezumab in switch patients. Effectiveness was evaluated based on reduction in average number of migraine days per month (MMDs), MIDAS and HIT-6 scores changes as well as in number of monthly days with acute migraine medication use. RESULTS: One hundred fifty-three out of 867 patients with a history of anti-CGRP pathway mAb treatment prior to initiation of fremanezumab were analysed. Switch to fremanezumab led to ≥ 50% MMD reduction in 42.8% of migraine patients, with higher response rate in EM (48.0%) than in CM patients (36.5%). A ≥ 30% MMD reduction was achieved by 58.7% in CM patients. After three months, monthly number of migraine days decreased by 6.4 ± 5.87 (baseline: 13.6 ± 6.5; p < 0.0001) in all patients, 5.2 ± 4.04 in EM and 7.7 ± 7.45 in CM patients. MIDAS scores decreased from 73.3 ± 56.8 (baseline) to 50.3 ± 52.9 (after 3 months; p = 0.0014), HIT-6 scores decreased from 65.9 ± 5.0 to 60.9 ± 7.2 (p < 0.0001). Concomitant use of acute migraine medication had decreased from 9.7 ± 4.98 (baseline) to 4.9 ± 3.66 (3 months) (p < 0.0001). CONCLUSIONS: Our results show that about 42.8% of anti-CGRP pathway mAb-non-responder benefit from switching to fremanezumab. These results suggest that switching to fremanezumab may be a promising option for patients experiencing poor tolerability or inadequate efficacy with prior other anti-CGRP pathway mAb use. TRIAL REGISTRATION: FINESSE Study is registered on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS44606).

Transcranial direct current stimulation to reduce chronic pelvic pain in endometriosis: phase II randomized controlled clinical trial.

BACKGROUND: It is known that various chronic pain conditions lead to maladaptive changes in the central nervous system. Endometriosis is frequently associated with chronic pelvic pain (CPP). Its sufficient treatment remains a clinical challenge. Transcranial direct current stimulation (tDCS) has been shown to be a powerful method to reduce chronic pain. Therefore, this study aimed to investigate pain reduction via anodal tDCS in patients with endometriosis and CPP. METHODS: This clinical phase II, placebo-controlled, randomized, parallel-design study included 36 patients with endometriosis and CPP. All patients had CPP, defined as a score of ≥3/10 on the visual analog scale for ≥3 months in the prior 6 months. Anodal or placebo tDCS (18 patients per arm) was applied over the primary motor cortex for 10 days. The primary outcome measure was the pressure pain threshold (objective pain measure), and secondary outcomes were the numerical rating scale score (subjective pain measure), Von Frey monofilaments, and disease- and pain-related questionnaires. Data were collected at baseline, after the 10-day stimulation, and at a follow-up session, which took place 1 week after the tDCS had ended. Statistical analyses were performed with analyses of variance and t tests. RESULTS: Significant decreased pain perception in both pain measurements (pressure pain threshold and numerical rating scale score) was found for the active tDCS group compared with the placebo group. This proof-of-concept study shows that tDCS is a helpful supporting pain therapy for patients with endometriosis and CPP. Moreover, further analyses revealed that 1 week after the stimulation had ended, pain reduction as indexed by pressure pain threshold remained significantly decreased, which indicates possible long-term analgesic effects. CONCLUSION: The present study provides evidence that tDCS is an effective therapy for pain reduction in endometriosis-associated CPP. The results support the notion that CPP is developed and maintained in the central nervous system, making a multimodal pain therapy necessary. TRIAL REGISTRATION: www.ClinicalTrials.gov ID: NCT05231239.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

Study Design and Protocol of a Randomized Controlled Trial of the Efficacy of a Smartphone-Based Therapy of Migraine (SMARTGEM).

Background: Digitalization and electronic health (eHealth) offer new treatment approaches for patients with migraine. Current smartphone applications (apps) for migraine patients include a wide spectrum of functions ranging from digital headache diaries to app-based headache treatment by, among others, analysis of the possible triggers, behavioral therapy approaches and prophylactic non-drug treatment methods with relaxation therapy or endurance sport. Additional possibilities arise through the use of modern, location-independent communication methods, such as online consultations. However, there is currently insufficient evidence regarding the benefits and/or risks of these electronic tools for patients. To date, only few randomized controlled trials have assessed eHealth applications. Methods: SMARTGEM is a randomized controlled trial assessing whether the provision of a new digital integrated form of care consisting of the migraine app M-sense in combination with a communication platform (with online consultations and medically moderated patient forum) leads to a reduction in headache frequency in migraine patients, improving quality of life, reducing medical costs and work absenteeism (DRKS-ID: DRKS00016328). Discussion: SMARTGEM constitutes a new integrated approach for migraine treatment, which aims to offer an effective, location-independent, time-saving and cost-saving treatment. The design of the study is an example of how to gather high quality evidence in eHealth. Results are expected to provide insightful information on the efficacy of the use of electronic health technology in improving the quality of life in patients suffering from migraine and reducing resource consumption.

Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience.

BACKGROUND: Migraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption. METHODS: Patients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13-16 of the drug holiday; 4) in weeks 9-12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period. RESULTS: This study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life. CONCLUSIONS: Reinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.

Functional Brain Changes Due to Chronic Abdominal Pain in Inflammatory Bowel Disease: A Case-Control Magnetic Resonance Imaging Study.

INTRODUCTION: Various chronic pain conditions go along with functional and structural brain changes. This study aimed to investigate functional and structural brain changes by magnetic resonance imaging (MRI) in inflammatory bowel disease (IBD) patients with chronic abdominal pain. METHODS: Sixty-four subjects were included in the final analysis (32 IBD patients with chronic abdominal pain; 32 age-matched and sex-matched controls). All patients suffered from chronic abdominal pain, defined as a score of ≥3/10 on the visual analog scale for at least 3 months in the past 6 months. Besides structural MRI, resting state functional MRI was used to compare functional connectivity of 10 networks between groups. RESULTS: Patients with IBD showed no structural brain alterations but a significantly increased resting state functional connectivity of the secondary somatosensory cortex within the salience network. DISCUSSION: Because the secondary somatosensory cortex saves sensory stimuli and compares novel information with latter experiences, these functions may be maladaptive in IBD patients with abdominal pain.

Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study.

BACKGROUND: National and international guidelines recommend stopping migraine prophylaxis with CGRP(-receptor) monoclonal antibodies after 6-12 months of successful therapy. In this study, we aimed to analyze the course of migraine for four months after the cessation of CGRP(-receptor) antibodies use. METHODS: This longitudinal cohort study included patients with migraine who received a CGRP-(receptor) antibody for ≥8 months before treatment cessation. We analyzed headache data in the four-week period prior to mAb treatment initiation (baseline), in the month before the last mAb injection, in weeks 5-8 and 13-16 after last treatment. Primary endpoint of the study was the change of monthly migraine days from the month before last treatment to weeks 13-16. Secondary endpoints were changes in monthly headache days and monthly days with acute medication use. RESULTS: A total of 62 patients equally distributed between prophylaxis with the CGRP-receptor antibody erenumab and the CGRP antibodies galcanezumab or fremanezumab participated in the study. Patients reported 8.2 ± 6.6 monthly migraine days in the month before last treatment. Monthly migraine days gradually increased to 10.3 ± 6.8 in weeks 5-8 (p = 0.001) and to 12.5 ± 6.6 in weeks 13-16 (p < 0.001) after drug cessation. Monthly migraine days in weeks 13-16 were not different from baseline values (-0.8 ± 5.4; p > 0.999). Monthly headache days and monthly days with acute medication use showed a similar pattern. CONCLUSIONS: The cessation of CGRP(-receptor) antibodies migraine prophylaxis was associated with a significant increase of migraine frequency and acute medication intake over time.

HIT-6 and EQ-5D-5L in patients with migraine: assessment of common latent constructs and development of a mapping algorithm.

OBJECTIVE: The aims of this study were to assess whether there is a conceptual overlap between the questionnaires HIT-6 and EQ-5D and to develop a mapping algorithm allowing the conversion of HIT-6 to EQ-5D utility scores for Germany. METHODS: This study used data from an ongoing randomised controlled trial for patients suffering from migraine. We assessed the conceptual overlap between the two instruments with correlation matrices and exploratory factor analysis. Linear regression, tobit, mixture, and two-part models were used for mapping, accounting for repeated measurements, tenfold cross-validation was conducted to validate the models. RESULTS: We included 1010 observations from 410 patients. The EQ-5D showed a substantial ceiling effect (47.3% had the highest score) but no floor effect, while the HIT-6 showed a very small ceiling effect (0.5%). The correlation between the instruments' total scores was moderate (- 0.30), and low to moderate among each domain (0.021-0.227). The exploratory factor analysis showed insufficient conceptual overlap between the instruments, as they load on different factors. Thus, there is reason to believe that the instruments' domains do not capture the same latent constructs. To facilitate future mapping, we provide coefficients and a variance-covariance matrix for the preferred model, a two-part model with the total HIT-6 score as the explanatory variable. CONCLUSION: This study showed that the German EQ-5D and the HIT-6 lack the conceptual overlap needed for appropriate mapping. Thus, the estimated mapping algorithms should only be used as a last resort for estimating utilities to be employed in economic evaluations.

Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study.

BACKGROUND: Switching between antibody classes might be a treatment option in migraine patients who have not responded to one class of a CGRP-(receptor) monoclonal antibody (mAb), but there are no efficacy data so far. In this real-world analysis, we assessed the treatment response to a CGRP-mAb in patients that have previously failed the CGRP-receptor-mAb erenumab. METHODS: We analyzed retrospective headache diary data of 78 patients with migraine who switched between CGRP-mAbs classes at four German headache centers either due to lack of efficacy or intolerable side effects. Among these, we identified 25 patients who did not respond to erenumab after three treatment cycles (defined as <30% reduction of monthly headache days) and had complete headache documentation at least one month before and during both treatments. We assessed the ≥30% responder rate at month three after switching from erenumab to a CGRP-mAb (galcanezumab or fremanezumab) (primary endpoint). Secondary endpoints included ≥50% responder rate, monthly headache days, and monthly days with acute medication use. In an exploratory subgroup analysis patients were stratified for daily and non-daily headache. RESULTS: The switch from erenumab to a CGRP-mAb led to a ≥30% response in one-third (32%) of the patients after three treatment cycles. A ≥50% response was achieved in 12% of the patients. Monthly headache days were reduced in month three compared to baseline (20.8 ± 7.1 to 17.8 ± 9.1; p = 0.009). Stratified analysis revealed that no patient with daily headache (n = 9) responded to the treatment switch, while a 30% response was achieved by 50% of patients with non-daily headache (n = 16). CONCLUSION: Our findings demonstrate that a relevant proportion of erenumab non-responders might benefit from a treatment switch to a CGRP-mAb. Switching seems to be a promising treatment option especially in migraine patients with non-daily headache.

Patients' and Health Care Workers' Perception of Migraine Images on the Internet: Cross-sectional Survey Study.

BACKGROUND: The representation of migraine in the media is stereotypical. Standard images of migraine attacks display stylish young women holding their head in a pain pose. This representation may contribute to the social stigmatization of patients with migraine. OBJECTIVE: We aimed to analyze how patients with migraine and health care workers perceive online images of migraine. METHODS: The study consisted of an anonymous web-based survey of patients with migraine at the Headache Center of Charité - Universitätsmedizin Berlin (migraine group) and employees and students at our university (health care group). A total of 10 frequently used Adobe Stock photos of migraine attacks were presented to the participants. Each photo was rated on a scale of 0% to 100% based on how closely it resembled a realistic migraine attack (realism score). Patients with migraine also indicated how much each photo corresponded to their own experience of migraine as a percentage (representation score). We calculated the mean realism and representation scores for all photos and conducted further analyses using the categories male or female models, younger or older models, and unilateral or bilateral pain pose. RESULTS: A total of 367 patients with migraine and 331 health care employees and students completed the survey. In both groups, the mean realism score was <50% (migraine group: 47.8%, SD 18.3%; health care group: 46.0%, SD 16.2%). Patients with migraine identified their own migraine experience in these photos to a lesser degree (mean representation score 44.4%, SD 19.8%; P<.001 when compared to the realism score). Patients and health care workers considered photos with male models to be more realistic than photos with females (P<.001) and photos with older models to be more realistic than those with younger people (P<.001). In the health care group only, a bilateral pain posture was deemed more realistic than a unilateral pose (P<.001). CONCLUSIONS: Standard images of migraine attacks are considered only slightly or moderately realistic by patients and health care workers. Some characteristics perceived as more realistic such as male sex or older age are in contrast with migraine epidemiology. A more accurate representation of migraine in the media could help to raise awareness for migraine and reduce the associated stigma.

Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis.

BACKGROUND: Head-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) pathway have not been published to date. OBJECTIVES: This study aimed to indirectly compare the clinical efficacy and safety of mAbs against CGRP or its receptor (CGRPR) and topiramate in episodic migraine prophylaxis using meta-analysis. METHODS: We included controlled trials testing efficacy and safety of erenumab, galcanezumab, fremanezumab, eptinezumab, and topiramate in adults diagnosed with episodic migraine. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from January 2000 to November 2020. We used the Risk of Bias 2 (RoB2) tool to assess the risk of bias and report pooled mean effects (mean difference and risk ratio) as estimated in a random effect model. For efficacy analysis, we determined the reduction of monthly migraine days (MMDs), reduction of days with acute medication (AMDs), and 50% responder rates (50% RR). For safety, we determined adverse events (AEs) occurring in ≥ 2% of study participants and the number of patients who discontinue treatment due to AEs (DAEs). The number needed to treat (NNT) and to harm (NNH) were estimated as well as the likelihood to help or harm (LLH). RESULTS: We included 13 trials involving 7557 patients: three trials with erenumab, two trials with galcanezumab, two trials with fremanezumab, one trial with eptinezumab, and five trials with topiramate, for the prophylaxis of episodic migraine in adults. The placebo-subtracted reduction (pooled mean difference) of MMDs were - 1.55 (95% CI - 1.86 to - 1.24; active drug n = 3326 vs placebo n = 2219, 8 studies) for the CGRP(R) mAb and - 1.11 (95% CI - 1.62 to - 0.59; active drug n = 1032 vs placebo n = 543, 4 studies) for topiramate (p for subgroup difference = 0.15). 'Cognitive' and 'sensory & pain'-related adverse events occurred more often in patients treated with topiramate compared with those treated with a CGRP(R) mAb (p for subgroup difference 0.03 and < 0.001, respectively). Based on the 50% RR and DAE, the NNT, NNH, and LHH for the CGRP(R) mAbs were 6, 130, and 24.3:1, respectively. For topiramate, these values were 7, 9, and 1.8:1, respectively. CONCLUSION: The efficacy of CGRP(R) mAbs to reduce migraine days does not differ from topiramate. However, the safety profile is in favor of the CGRP(R) mAbs, with a higher likelihood to help than to harm compared with topiramate. The diversity of endpoint determination and the heterogeneity between studies for some endpoints cause some limitations for this study.

Determining the Evolution of Headache Among Regular Users of a Daily Electronic Diary via a Smartphone App: Observational Study.

BACKGROUND: Smartphone-based apps represent a major development in health care management. Specifically in headache care, the use of electronic headache diaries via apps has become increasingly popular. In contrast to the soaring volume of available data, scientific use of these data resources is sparse. OBJECTIVE: In this analysis, we aimed to assess changes in headache and migraine frequency, headache and migraine intensity, and use of acute medication among people who showed daily use of the headache diary as implemented in the freely available basic version of the German commercial app, M-sense. METHODS: The basic version of M-sense comprises an electronic headache diary, documentation of lifestyle factors with a possible impact on headaches, and evaluation of headache patterns. This analysis included all M-sense users who had entered data into the app on a daily basis for at least 7 months. RESULTS: We analyzed data from 1545 users. Mean MHD decreased from 9.42 (SD 5.81) at baseline to 6.39 (SD 5.09) after 6 months (P<.001; 95% CI 2.80-3.25). MMD, AMD, and migraine intensity were also significantly reduced. Similar results were found in 985 users with episodic migraine and in 126 users with chronic migraine. CONCLUSIONS: Among regular users of an electronic headache diary, headache and migraine frequency, in addition to other headache characteristics, improved over time. The use of an electronic headache diary may support standard headache care.

Primary headaches during the COVID-19 lockdown in Germany: analysis of data from 2325 patients using an electronic headache diary.

BACKGROUND: Lockdown measures due to the COVID-19 pandemic have led to lifestyle changes, which in turn may have an impact on the course of headache disorders. We aimed to assess changes in primary headache characteristics and lifestyle factors during the COVID-19 lockdown in Germany using digital documentation in the mobile application (app) M-sense. MAIN BODY: We analyzed data of smartphone users, who entered daily data in the app in the 28-day period before lockdown (baseline) and in the first 28 days of lockdown (observation period). This analysis included the change of monthly headache days (MHD) in the observation period compared to baseline. We also assessed changes in monthly migraine days (MMD), the use of acute medication, and pain intensity. In addition, we looked into the changes in sleep duration, sleep quality, energy level, mood, stress, and activity level. Outcomes were compared using paired t-tests. The analysis included data from 2325 app users. They reported 7.01 ± SD 5.64 MHD during baseline and 6.89 ± 5.47 MHD during lockdown without significant changes (p > 0.999). MMD, headache and migraine intensity neither showed any significant changes. Days with acute medication use were reduced from 4.50 ± 3.88 in the baseline to 4.27 ± 3.81 in the observation period (p < 0.001). The app users reported reduced stress levels, longer sleep duration, reduced activity levels, along with a better mood, and an improved energy level during the first lockdown month (p ≤ 0.001). In an extension analysis of users who continued to use M-sense every day for 3 months after initiation of lockdown, we compared the baseline and the subsequent months using repeated-measures ANOVA. In these 539 users, headache frequency did not change significantly neither (6.11 ± 5.10 MHD before lockdown vs. 6.07 ± 5.17 MHD in the third lockdown month, p = 0.688 in the ANOVA). Migraine frequency, headache and migraine intensity, and acute medication use were also not different during the entire observation period. CONCLUSION: Despite slight changes in factors that contribute to the generation of headache, COVID-19-related lockdown measures did not seem to be associated with primary headache frequency and intensity over the course of 3 months.