Validity and reliability of Arabic version of pediatric migraine disability assessment scale (Child Self-Report versus Parent Proxy-Report): a multi-center study.

BACKGROUND: Pediatric Migraine Disability Assessment (PedMIDAS) is one of the most frequently used questionnaires to assess disability from migraine in pediatric patients. This work aimed to evaluate the validity and test-retest reliability of the Arabic version of the child self-report versus the parent proxy report PedMIDAS. We also aimed to test the agreement between children's and parents' reports of the scale. METHODS: PedMIDAS was subjected to translation and back-translation, then applied to 112 pediatric patients fulfilling the migraine diagnostic criteria. This cross-sectional study was conducted on two visits, one week apart. At visit 1, the following data were obtained from the included pediatric patients: disease duration, migraine type, current treatment regimen, monthly migraine days (MMD) during the last month preceding the enrollment, and migraine intensity using the visual analogue scale. Then, each child and his parent were independently asked to fill out PedMIDAS and Child Self-Report of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) to test the convergent validity of PedMIDAS. At visit 2, each child was requested to complete PedMIDAS again, and so was the parent to evaluate test-retest reliability. RESULTS: Cronbach's alpha was estimated to be 0.94 for each instrument. For the child-self report PedMIDAS, the average measure intraclass correlation coefficient (ICC) value was 0.992 (95%CI = 0.989-0.995), while it was estimated to be 0.990 for the parent-proxy report with 95%CI = 0.985-0.993, indicating excellent test-retest reliability for both instruments. The child-self report and the parent-proxy report PedMIDAS scores were significantly correlated with MMD, VAS, and all domains of the corresponding PedsQL, supporting convergent validity for both instruments. Agreement between parent and child on disability grading categories of PedMIDAS was substantial (κ = 0.644). CONCLUSION: The Arabic version of PedMIDAS was a valid and reliable instrument to assess disability from migraine in Arabic-speaking pediatric patients with migraine. Parent reports can be valuable as a complement to child reports for a comprehensive assessment of migraine.

Real-world experience with monthly and quarterly dosing of fremanezumab for the treatment of patients with migraine in Japan.

Background: The effectiveness of fremanezumab in treating migraine has been demonstrated in randomized controlled trials. However, real-world study results are still limited. Methods: We conducted a single-center, observational study that included patients with episodic migraine (EM) and chronic migraine (CM) who received fremanezumab monthly or quarterly over 6-month periods. The primary outcome of this study was to evaluate changes in monthly migraine days (MMD) and responder achievement after treatment with fremanezumab. The secondary aim was to characterize the predictors of responder at 6 months. We also evaluated the effectiveness of fremanezumab in the patients who switched from other calcitonin gene-related peptide (CGRP) monoclonal antibodies, and compared the effectiveness of fremanezumab between the monthly and quarterly dosing groups. One hundred twenty-seven patients with migraine (age, 45.2 ± 12.6 years; 96 women) who received at least one dose of fremanezumab with ≥3 months of follow-up were included. The number of MMD was assessed by headache diary. Results: The changes in MMD from baseline at 1, 3, and 6 months were -6.1 ± 4.7, -7.7 ± 4.4, and - 8.5 ± 4.5 days in the total cohort, respectively (p < 0.001). The ≥50%, ≥ 75 and 100% responder rates at 6 months were 67.6, 22.5, and 5.4% in the total cohort, 90.4, 36.5, and 9.6% in the EM group, and 52.2, 14.9, and 1.5% in the CM group, respectively. Fremanezumab was also effective in 35 patients who switched from other CGRP monoclonal antibodies. Quarterly and monthly fremanezumab doses were equally effective in MMD reduction in the EM and CM groups. In the CM group, 65.1% experienced remission to EM after 6 months. Adverse reactions were mild and occurred in 9.5% of total patients. An at least ≥50% reduction in MMD from months 1 to 3 better predicted a ≥ 50% reduction in MMD at 6 months with 90.5% sensitivity and 80.6% specificity (p < 0.001). Conclusion: In our real-world study, quarterly and monthly fremanezumab dosing showed both favorable effectiveness and tolerability in patients with migraine.

Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study.

BACKGROUND: In real-world studies, it is unclear whether galcanezumab has a significant effect in the first week after administration. METHODS: We retrospectively assessed 55 high-frequency episodic migraine (HFEM) and chronic migraine patients who received three galcanezumab doses. Mean changes in the numbers of weekly migraine days (WMDs) during month 1 and migraine days per month (MMDs) after 1-3 months of treatment were obtained. Clinical factors related to a ≥ 50% response rate (RR) at month 3 were analyzed. The prediction of ≥ 50% responders at month 3 using different weekly RRs at week 1 (W1) was evaluated. The RR at W1 was calculated with the following formula: RR (%) = 100 - [(WMDs at W1/baseline WMD) × 100]. RESULTS: The number of MMDs significantly improved from baseline to 1, 2 and 3 months. The ≥ 50% RR was 50.9% at 3 months. The number of WMDs decreased significantly from baseline to week 1 (- 1.6 ± 1.7 days), week 2 (- 1.2 ± 1.6 days), week 3 (- 1.0 ± 1.3 days), and week 4 (- 1.1 ± 1.6 days) during month 1. The RR at W1 was largest (44.6 ± 42.2%). The ≥ 30%, ≥ 50% and ≥ 75% RRs at W1 were significantly predictive of a ≥ 50% RR at 3 months. Logistic regression analysis predicting a ≥ 50% RR at month 3 showed that the RR at W1 was the sole contributing factor. CONCLUSION: In our study, galcanezumab showed a significant effect in the first week after administration, and the RR at W1 could predict the RR at 3 months.

Effectiveness of three calcitonin gene-related peptide monoclonal antibodies for migraine: A 12-month, single-center, observational real-world study in Japan.

BACKGROUND: Real-world data on the effectiveness of calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in migraine patients are needed. METHODS: We performed a single-center, real-world study with an observation period of up to 12 months (mean 7.5 ± 3.4 months) after CGRP mAb administration. A total of 228 Japanese patients with episodic or chronic migraine (age, 45.9 ± 13.2 years; 184F; 45 erenumab; 60 galcanezumab; 123 fremanezumab) who were treated with CGRP mAbs for at least three months were ultimately included in this study. RESULTS: In the total cohort, after CGRP mAb treatment, mean monthly migraine days decreased by 7.2 ± 4.8, 8.3 ± 4.7, and 9.5 ± 5.0 at three, six and 12 months, respectively. The ≥50% monthly migraine day reduction rates at three, six and 12 months were 48.2%, 61.0% and 73.7%, respectively. In the logistic regression analysis, the presence of osmophobia and fewer baseline monthly migraine days contributed to ≥50% responders at three, six and 12 months. The ≥50% responders at three or six months were useful in predicting ≥50% responders at 12 months. In subgroups of patients with difficult-to-treat migraine (those with medication overuse headache or psychiatric comorbidities) and previous CGRP mAb users, monthly migraine days were substantially reduced over 12 months. There was no difference in monthly migraine day reduction over 12 months among three different CGRP mAbs. Adverse reactions were observed in 28 (12.3%) patients, with injection site reactions being the most common (n = 22) though generally mild in severity. CONCLUSION: This real-world study confirmed the efficacy and safety of three different CGRP mAbs for prophylactic treatment of patients with migraine.

Defining migraine days, based on longitudinal E-diary data.

BACKGROUND: There is a need for standardization of the definition of a migraine day for clinical and research purposes. METHODS: We prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of ≥4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. RESULTS: Of all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to ≥30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. CONCLUSION: We propose to define a migraine day as follows: 1) (a) headache duration ≥30 minutes; (b) matching ≥2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache ≥1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect.

Efectividad de anticuerpos monoclonales anti-PRGC en el tratamiento preventivo de la migraña: estudio prospectivo de 63 pacientes / Effectiveness of anti-CGRP monoclonal antibodies in the preventive treatment of migraine: A prospective study of 63 patients

Introducción: El péptido relacionado con el gen de la calcitonina (PRGC) ha supuesto una revolución en el conocimiento de la fisiopatología de la migraña y ha llevado al desarrollo de nuevos fármacos específicos contra esta nueva diana.MétodosPresentamos un estudio prospectivo de 63 pacientes con migraña episódica (ME) y crónica (MC) tratados con anticuerpos monoclonales anti-PRGC y describimos su eficacia, seguridad y recaídas tras su suspensión. Se analizan predictores de respuesta que puedan ayudar a planificar mejor los tratamientos.ResultadosLa edad media fue de 48,3 ± 11,81 años, siendo 84,1% mujeres. La media de días de migraña al mes (DMM) fue de 15,59 días; 63,5% tenían MC. En todos se comenzó con erenumab 70 mg subcutáneo. Se aumentó la dosis a 140 mg en 47,6% de los pacientes. Se obtuvo una reducción entre 49,85 y 59,53% de DMM entre los tres primeros meses y el año de tratamiento; 17,5% presentó estreñimiento y 4,8% reacción en el lugar de la inyección. En cinco pacientes (17,9%) se cambió el tratamiento a galcanezumab. Tras suspender el tratamiento 23 pacientes sufrieron recaídas, con buena respuesta al reintroducirlo. No hemos podido establecer predictores de respuesta, pero sí observamos de forma estadísticamente significativa mayor número de días de mejora cuantos más DMM hubiera al inicio (p = 0,002).ConclusionesLos anticuerpos monoclonales anti-PRGC son fármacos eficaces, seguros y bien tolerados. Observamos que su interrupción, en algunos casos, puede conllevar recaídas frecuentes y precoces, por lo que recomendamos prolongar el tratamiento en aquellos pacientes con mayor DMM. (AU)

Introduction: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease.MethodsWe present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan.ResultsAverage age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002).ConclusionsAnti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM. (AU)

[Effectiveness of anti-CGRP monoclonal antibodies in the preventive treatment of migraine: A prospective study of 63 patients]. / Efectividad de anticuerpos monoclonales anti-PRGC en el tratamiento preventivo de la migraña: estudio prospectivo de 63 pacientes.

INTRODUCTION: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease. METHODS: We present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan. RESULTS: Average age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002). CONCLUSIONS: Anti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM.

Health State Utility Mapping of Rimegepant for the Preventive Treatment of Migraine: Double-Blind Treatment Phase and Open Label Extension (BHV3000-305).

INTRODUCTION: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values. METHODS: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. RESULTS: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. CONCLUSION: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. TRIAL REGISTRATION: NCT03732638.

Oral Cannabinoid Preparations for the Treatment of Chronic Migraine: A Retrospective Study.

OBJECTIVE: To explore the effectiveness and safety of three oral cannabinoid preparations (FM2®, Istituto farmaceutico militare, Firenze, Italy; Bedrocan®, Bedrocan International, Vandaam, Netherlands; and Bediol®, Bedrocan International, Vandaam, Netherlands) in the treatment of chronic migraine. DESIGN: Retrospective, cohort study. SUBJECTS: Patients with chronic migraine who received FM2, Bedrocan, or Bediol daily for the off-label treatment of their headache, for up to 6 months. METHODS: The number of migraine days per month, pain intensity, the number of acute medications taken per month, the number of days per month on which the patient took at least one acute medication, and adverse events were recorded at baseline and at 3 months and 6 months after the start of treatment with oral cannabinoid preparations. RESULTS: The number of migraine days did not change significantly after the third month or the sixth month when compared with baseline (P = 0.1182). The pain intensity (P = 0.0004), the acute medication consumption (P = 0.0006), and the number of days per month in which patients took at least one acute medication significantly decreased when compared with baseline (P = 0.0004). No significant differences were found between patients who were still taking a preventive treatment for chronic migraine and those who were not (all P > 0.05). Different oral cannabinoid preparations displayed similar levels of effectiveness (all P > 0.05). The adverse events were mostly mild and occurred in 43.75% of patients. CONCLUSIONS: Oral cannabinoid preparations may have a role in reducing pain intensity and acute medication intake in patients with chronic migraine, but the magnitude of the effect seems modest; further studies are needed.

Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation.

INTRODUCTION: Episodic migraine is a debilitating condition associated with vast impairments of health, daily living, and life quality. Several prophylactic treatments exist, having a moderate ratio of action related to side effects and therapy costs. Repetitive transcranial magnetic stimulation (rTMS) is an evidence based therapy in several neuropsychiatric conditions, showing robust efficacy in alleviating specific symptoms. However, its efficacy in migraine disorders is unequivocal and might be tightly linked to the applied rTMS protocol. We hypothesized that multifocal rTMS paradigm could improve clinical outcomes in patients with episodic migraine by reducing the number of migraine days, frequency and intensity of migraine attacks, and improve the quality of life. METHODS: We conducted an experimental, double-blind, randomized controlled study by applying a multifocal rTMS paradigm. Patients with episodic migraine with or without aura were enrolled in two centers from August 2018, to December 2019, and randomized to receive either real (n = 37) or sham (sham coil stimulation, n = 28) multifocal rTMS for six sessions over two weeks. Patients, physicians, and raters were blinded to the applied protocol. The experimental multifocal rTMS protocol included two components; first, swipe stimulation of 13 trains of 140 pulses/train, 67 Hz, 60% of RMT, and 2s intertrain interval and second, spot burst stimulation of 33 trains of 15 pulses/train, 67 Hz, 85% of RMT, and 8s intertrain interval. Reduction >50% from the baseline in migraine days (as primary outcome) and frequency and intensity of migraine attacks (as key secondary outcomes) over a 12-week period were assessed. To balance the baseline variables between the treatment arms, we applied the propensity score matching through the logistic regression. RESULTS: Among 65 randomized patients, sixty (age 39.7 ± 11.6; 52 females; real rTMS n = 33 and sham rTMS n = 27) completed the trial and five patients dropped out. Over 12 weeks, the responder's rate in the number of migraine days was significantly higher in the real rTMS compared to the sham group (42% vs. 26%, p < 0.05). The mean migraine days per month decreased from 7.6 to 4.3 days in the real rTMS group and from 6.2 to 4.3 days in the sham rTMS group, resulting in a difference with real vs. sham rTMS of -3.2 days (p < 0.05). Similarly, over the 12-week period, the responder's rate in the reduction of migraine attacks frequency was higher in the real rTMS compared to the sham group (42% vs 33%, p < 0.05). No serious adverse events were observed. CONCLUSION: Our pilot study shows compelling evidence in a double placebo-controlled trial that multifocal rTMS is an effective and well-tolerated preventive treatment in patients with episodic migraine.

Matching-adjusted indirect comparisons of oral rimegepant versus placebo, erenumab, and galcanezumab examining monthly migraine days and health-related quality of life in the treatment of migraine.

OBJECTIVE: Rimegepant is an orally administered small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, with demonstrated efficacy in the acute treatment of migraine. Recent estimates from a single-arm trial (BHV3000-201) have also shown evidence of long-term preventive effects in monthly migraine days (MMDs) and health-related quality of life (HRQoL). This study aimed to compare MMDs and HRQoL data for oral rimegepant to those obtained in placebo-controlled trials for injectable anti-CGRP monoclonal antibodies (mAbs) galcanezumab and erenumab. METHODS: Matching-adjusted indirect comparisons (MAICs) were conducted using rimegepant subject-level data and published aggregate-level results from mAb trials. Rimegepant baseline characteristics were matched to the pooled subject characteristics from EVOLVE-I/II (galcanezumab vs. placebo; n = 1773) and STRIVE (ereumab vs. placebo; n = 955) by reweighting the rimegepant subjects to more closely match the distributions observed in these trials. To align with inclusion criteria of the mAb trials, only the subset of rimegepant subjects with a history of 4-14 MMDs were included (n = 257). Weighted mean differences were used to calculate adjusted change in MMDs, Migraine Disability Assessment Test (MIDAS) score, and Migraine-Specific Quality of Life Questionnaire version 2 (MSQv2) scores from baseline to week 12. RESULTS: When matched to the EVOLVE trials, rimegepant was superior to placebo with a mean difference in MMD change from baseline [95% confidence interval] of -1.16 [-1.80, -0.52] and was not statistically significantly different from galcanezumab 0.59 [-0.13, 1.32]. When matched to the STRIVE trial, rimegepant was superior to placebo -1.59 [-2.15, -1.03] and was not statistically significantly different from erenumab -0.06 [-0.61, 0.50]. Rimegepant showed superior MIDAS and MSQv2 results compared with placebo in both EVOLVE trials and in the STRIVE trial, no statistically significant differences from galcanezumab and erenumab regarding MIDAS, and favorable results compared with erenumab across all MSQv2 domains, while being generally similar to galcanezumab across all MSQv2 domains. CONCLUSIONS: When adjustments were made to reflect baseline characteristics in published literature, supporting data from BHV3000-201 suggest that rimegepant every other day is an effective therapy in reducing disability and MMDs and enhancing migraine-specific HRQoL. These data support the preventive benefit observed in randomized trials of rimegepant and further validate its efficacy for both acute and preventive treatment of migraine.

Erenumab prevents the occurrence of migraine attacks and not just migraine days: Post-hoc analyses of a phase III study.

BACKGROUND: This post-hoc analysis was conducted to evaluate the effect of erenumab on monthly migraine days, monthly migraine attacks, and attack duration in patients with episodic migraine to investigate whether erenumab actually prevents the occurrence of migraine attacks and/or shortens them. METHODS: We conducted a post-hoc analysis of the data from the STRIVE study, in 955 patients with episodic migraine. Relative changes from baseline to mean over months 4, 5 and 6 of the double-blind treatment phase in monthly migraine days, monthly migraine attacks and mean migraine attack duration were assessed. RESULTS: Erenumab reduced monthly migraine days and monthly migraine attacks compared with placebo in a similar way. Erenumab had only a minor impact on shortening the duration of migraine attacks. CONCLUSION: These post-hoc analyses demonstrate that the decrease in monthly migraine days by erenumab is mainly driven by a reduction in the frequency of monthly migraine attacks and to a much lesser extent by shortening the duration of migraine attacks.Trial registration: This study is registered at ClinicalTrials.gov (NCT02456740).

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial.

BACKGROUND: Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. OBJECTIVE: To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. MATERIALS AND METHODS: The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. RESULTS: Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups. CONCLUSIONS: This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Problematic presentation and use of efficacy measures in current trials of CGRP monoclonal antibodies for episodic migraine prevention: A mini-review.

BACKGROUND: In trials of monoclonal antibodies against calcitonin gene-related peptide or its receptor for prevention of episodic migraine, we observed two problematic aspects: a) The graphic presentations; b) the methods of calculating "response rates" (≥50% decrease of monthly migraine days from baseline). OBSERVATIONS: Decrease in monthly migraine days is presented, over time, in figures on a downward (negative) scale from zero at baseline, with the ordinate stopped just beyond the maximum effect of the active drugs. In one trial, decreases in monthly migraine days were -1.8 after placebo, -3.2 after erenumab 70 mg and -3.7 after erenumab 140 mg, with the ordinate stopped at -4.5. The reader can perceive only a relative 2-fold benefit of erenumab versus placebo. If, however, treatment periods are compared with baseline in bar charts, MMDs persisting after treatment in the same trial can be illustrated as follows, creating a different perception: 78% for placebo, 61% for erenumab 70 mg, and 55% for erenumab 140 mg. In the nine trials, "response rates" defined as above were calculated in five different ways, taking different numbers of treatment months into account in comparisons with the one-month baseline. This makes comparisons impossible. SUGGESTIONS FOR IMPROVEMENTS: Mean monthly migraine days before and after treatment should be presented in a bar chart. Such figures, presenting persisting MMDs, are more clinically relevant and less misleading than decreases from baseline. The definition and methods of calculating and presenting "50% response rates" should be standardized by the Drug Trial Committee of the International Headache Society.

The spectrum of response to erenumab in patients with chronic migraine and subgroup analysis of patients achieving ≥50%, ≥75%, and 100% response.

OBJECTIVE: To assess the efficacy of erenumab across the spectrum of response thresholds (≥50%, ≥75%, 100%) based on monthly migraine days (MMD) reduction in patients with chronic migraine from a 12-week, randomized study (NCT02066415). METHODS: Patients (n = 667) received (3:2:2) placebo or erenumab 70/140 mg once-monthly. The proportion of patients achieving a given response threshold was assessed. A post-hoc analysis was conducted to contextualize the actual treatment benefit in subgroups of patients achieving (or not) specified response thresholds. Outcome measures included MMD, acute migraine-specific medication treatment days (MSMD) and disability. RESULTS: The proportion of patients responding to erenumab exceeded that of placebo at the ≥50% and ≥75% response thresholds. At month 3, 39.9% and 41.2% of patients on erenumab 70 and 140 mg, respectively, achieved ≥50% response versus placebo (23.5%). Similarly, at month 3, 17.0% and 20.9% of patients on erenumab 70 and 140 mg, respectively, achieved ≥75% response versus placebo (7.8%). Compared with the overall erenumab-treated population (change in MMD: -6.6 [both 70 and 140 mg]), ≥50% responders showed MMD reductions of -12.2/-12.5 for 70 mg/140 mg versus -2.6/-2.2 for those not achieving ≥50% response. ≥75% responders showed MMD reductions of -13.9/-14.8 for 70 mg/140 mg versus -5.0/-4.3 for those not achieving ≥75% response. Relative improvements in MSMD and disability were observed in responders versus overall erenumab-treated population. CONCLUSION: For erenumab-treated patients achieving ≥50% response, the actual reduction in MMD was almost twice that of the overall population. These findings provide context for setting realistic expectations regarding actual treatment benefit experienced by patients responding to treatment.

Real-world insights on the management of migraine patients: an Italian nationwide study.

Objectives: Understanding migraine management using data from a sample of patients representative of the Italian general adult population.Methods: Retrospective analysis on IQVIA Italian Longitudinal Patient Database. Two cohorts were created. (a) The triptan user cohort included patients with triptan prescriptions between November 2015 and October 2016. Migraine days were estimated counting triptan and indometacin/caffeine/prochlorperazine (ICP) pills prescribed during the 6 months following first triptan prescription. Patients were categorized as having episodic (EM) or chronic (CM) migraine based on the number of migraine days following International Classification of Headache Disorders criteria. (b) The migraine preventive treatment (MPT) user cohort included patients with MPT prescriptions during the period June 2016-May 2017. MPTs considered included beta-blockers, calcium-channel blockers, antiepileptics, antidepressants and antiserotoninergics. Migraine days experienced by MPTs users were estimated counting triptan and ICP pills prescribed during the 6 months following the most recent MPT prescription, while the number of MPT switches was estimated based on MPT prescriptions during the previous two years.Results: There were 9461 patients with triptan prescriptions to treat migraine acute attacks, which accounted yearly for 0.8% of general adult population. CM patients accounted for 3% of triptan users. There were 2004 patients prescribed with MPTs, which accounted for 0.16% of general adult population. Overall, among MPT users, 291 (15%) were still experiencing at least four migraine days/month, with this proportion increasing with the increase in the number of MPT switches.Conclusions: Results from this study suggest an unmet need in the management of migraine: too many patients did not receive MPTs, with this potentially due to several reasons requiring further investigations. Furthermore, even among patients receiving MPTs, disease control level with now available drugs seems to be sub-optimal.