Gender Differences in 3-Month Outcomes of Erenumab Treatment—Study on Efficacy and Safety of Treatment With Erenumab in Men

Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor.Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9–12 of treatment compared with baseline: 0–29%, 30–49%, 50–75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9–12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes.Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9–12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50–74% response, 35 (13.7%) had a 30–49% response, and 86 (33.6%) had a 0–29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes.Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.

Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4–7 migraine days/month, n = 22) and high frequency (8–14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study

Background Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18–45 years and > 45 years) and sex. Methods In the FOCUS study, eligible participants were randomized (1:1:1) to 12 weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18–45 and > 45 years) and sex subgroups. Results The modified intention-to-treat population (received ≥ 1 dose of study drug and had ≥ 10 days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18–45 years, n = 373; > 45 years, n = 464; male, n = 138; female, n = 699). Consistent reductions in monthly average number of migraine days during 12 weeks were observed, regardless of age (18–45 years: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.7 days; placebo, − 0.9 days; P < 0.001; > 45 years: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.7 days; placebo, − 0.3 days; P < 0.001) and sex (male: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.6 days; placebo, − 0.3 days; P < 0.001; female: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.9 days; placebo, − 0.6 days; P < 0.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups. Conclusions These results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex. Trial registration ClinicalTrials.gov Identifier NCT03308968 (FOCUS), registered October 13, 2017.

The burden of medication overuse headache and patterns of switching and discontinuation among triptan users: a systematic literature review

Background A synthesis of real-world discontinuation and switching patterns among triptan users and rates of acute medication use among patients with medication overuse headache (MOH) is needed to better understand the burden among patients with migraine. The study objectives were to: (1) synthesize rates of switching and discontinuation from triptans; (2) characterize acute medication use among patients with MOH; and (3) describe the associated burden. Methods A systematic literature review was conducted, under the Preferred Reporting Items for Systematic Review guidelines, using MEDLINE/EMBASE from database inception to July 2019. The search strategy targeted studies of adults with migraine, and included terms related to migraine and its treatment. Continuous variables were summarized using means, standard deviations, and ranges. Dichotomous and categorical variables were summarized using the number and proportion of individuals. Results Twenty studies were included; seven describing patterns of switching and discontinuation among triptan users, and 13 characterizing triptan overuse among patients with MOH. High rates of switching to non-specific acute medications and low two-year retention rates were reported; among US samples switching to opioids at the first refill (18.2%) or after 1-year (15.5%) was frequent. Compared to persistent use of triptans, switchers experienced greater headache related impact and either no improvement or increased headache-related disability. Rates of medication overuse by agent among patients with MOH varied greatly across the included studies, and only one study described factors associated with the risk of MOH (e.g. duration of medication overuse). Medication agent, increased headache frequency (p = .008), and increased disability (p = .045) were associated with unsuccessful withdrawal; patients overusing triptans were more successful at withdrawal than those overusing opioids or combination analgesics (P < .0001). Conclusions The evidence summarized here highlights that rates of WCS are low and many patients turn to other acute medication at their first refill. Patients may experience no improvement in disability when switching from one triptan agent to another, or experience increasing disability and/or increasing migraine frequency when turning to traditional acute treatment for migraine. Variability in health care settings, patient severity, and study design contributed to heterogeneity across the synthesis.

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.

Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

Background In daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort. Methods This is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment. Results Of 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049). Conclusions In real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.

Analysis of Influencing Factors of Acute Medication Poisoning in Adults in Emergency Department of Our Hospital from 2016 to 2019 and Observation of Curative Effect of Optimizing Emergency Procedures

Objective. This study analyzed the influencing factors of acute medication poisoning in adults in the emergency department of our hospital from January 2016 to December 2019 and observed the curative effect of optimizing emergency procedures on adult acute medication poisoning. Our results showed that, among all acute drug poisoning patients, the most common poisoning drug was sleeping pills (24.22%), followed by painkillers (20.31%) and antipsychotics (16.41%). Education level, drug category, drug source, drug dosage, unknown drug composition, and medication side effect were all influencing factors of acute drug poisoning. High school education level or below, self-purchasing medicine, medication overdose, unknown drug composition, and medication side effect were the risk factors of acute medication poisoning. In addition, after the nursing management of optimizing emergency procedures for this type of patients, the rescue time, observation time, and hospital stay of the patients had been shortened, the incidence of complications was low, the rescue success rate was high, and the clinical application effect was good.

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.

Real-Life Analysis with Erenumab: First Target Therapy in the Episodic and Chronic Migraine’s Prophylaxis

Background: to research retrospectively the efficacy of Erenumab’s treatment, thus allowing to describe a summary more in line with the reality observed every day in clinical practice, relative to a sample of patients widely heterogeneous. The study aims to confirm the efficacy of Erenumab, in terms of reduction of migraine days per month, from baseline to month 12 of treatment. Additional objectives included a reduction in the number of days of symptomatic drug use and change from baseline in the Migraine Disability Assessment Score Questionnaire (MIDAS); Methods: the analysis included all patients treated for 12 months with Erenumab during the year 2019–2020. The population analyzed consists of twenty-six patients from the Neurology outpatient clinic in Fossombrone. Several quantitative and qualitative variables were recorded by reading the medical records of the patients. The MIDAS was administered to patients to assess the disability related to migraine; Results: at the end of treatment, a statistically significant reduction in the mean number of monthly migraine days, acute medication use per month, and MIDAS questionnaire score was observed; Conclusions: as a preventive treatment of episodic and chronic migraine, our analysis data confirm the efficacy of Erenumab for the prevention of the migraine. The success is achieved in 96% of cases.

Comparing Perimenstrual and Nonperimenstrual Migraine Attacks Using an e-Diary

BackgroundEndogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to non-perimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms.ObjectivesTo compare perimenstrual and non-perimenstrual migraine attack characteristics and assess premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache E-diary. Characteristics of perimenstrual attacks and non-perimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in those without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and non-menstrually related migraine (non-MRM), and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of n=500 participants completed the E-diary for at least one month. Perimenstrual migraine attacks (n=998) compared with non-perimenstrual attacks (n=4097) were associated with longer duration (20.0 vs 16.1 hours, 95%CI [0.2-0.4]), higher recurrence risk (OR 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3- -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]) and less aura (OR 0.8 [0.6-1.0]). In total 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs. 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.