Efficacy and safety of anti-CGRP(r) monoclonal antibodies in real clinical practice: preliminary analysis after three months of therapy

Monoclonal antibodies inhibiting calcitonin gene related peptide (CGRP) or its receptor have been widely used for migraine prophylactic therapy for the past three years. Evaluation of their efficacy and safety of therapy in real clinical practice is needed.Objective: to evaluate the efficacy and safety of Erenumab, a monoclonal antibody inhibiting the CGRP receptor during three months of therapy.Patients and methods. Sixty-eight patients (58 women and 10 men, mean age 37±10.4 years) with episodic or chronic migraine who were treated with Erenumab were observed. Patients were assessed with MIDAS, WPAI, and HADS scales; the presence of cutaneous allodynia was evaluated with ASC-12 questionnaire. Patients kept a headache diary and marked adverse events during the whole treatment period.Results and discussion. 47 patients (69%) had chronic migraine and 32 (71.9%) had medication overuse headache. In 48 patients (70%) after 3 injections of Erenumab the number of days with migraine decreased by 50% or more. In 7 patients (10%), the reduction in headache days was more than 75%; 20 (29%) did not experience sufficient effect after three months of therapy. Nineteen adverse events were noted in 15 (22%) patients. Severe constipation led to discontinuation of treatment in two patients (3%).Conclusion. The study showed the efficacy and safety of Erenumab for migraine prophylaxis in both patients with episodic and chronic migraine.

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.

Heart Rate Variability Predicts Treatment Efficacy in Patients with Chronic Migraine: An Exploratory Study

Background : Chronic migraine (CM) is a disabling headache disorder. Autonomic nervous system (ANS) disturbance, as evidenced from heart rate variability (HRV) studies, has been documented in patients with episodic migraine and other pain disorders but not specifically in patients with CM. This study aimed to explore whether the HRV in patients with CM was impaired and whether it could be used to predict treatment outcomes.Methods : Patients with CM were recruited, along with age- and gender-matched healthy controls (CTLs). The time-domain, frequency-domain, and nonlinear metrics of HRV were calculated to evaluate the sympathetic and parasympathetic aspects of ANS function in patients with CM before and after 3-month (12 weeks) treatment with flunarizine as well as in CTLs. The patients were asked to keep a headache diary throughout the study period to determine the treatment efficacy.Results : A total of 81 patients with CM and 58 CTLs completed the study. Most HRV values in patients with CM were significantly lower than those in CTLs, suggesting decreased overall autonomic modulation and parasympathetic hypofunction but not sympathetic dysfunction. By unsupervised clustering analysis, patients with CM were divided into two cluster groups with high and low HRV at baseline. Patients with high baseline HRV, which was comparable to that of CTLs, showed significantly higher absolute and relative reductions in averaged monthly headache days across a 3-month preventive treatment compared with patients with low baseline HRV (-9.1 days vs. -6.4 days or -43.2% vs. -30.1%, both p < 0.05). The HRV increased after preventive treatment in the low-HRV group but not in the high-HRV group.Conclusions : HRV could distinguish patients with CM from CTLs, indicating the involvement of ANS dysfunction. Moreover, patients with CM having a near-normal baseline HRV, indicating a preserved parasympathetic function and overall ANS modulation reservoir, predicted a better outcome to preventive treatment with flunarizine than those with low HRV.Trial registration: Neurologic Signatures of Chronic Pain Disorders, NCT02747940.Registered 22 April 2016, https://clinicaltrials.gov/ct2/show/NCT02747940

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.

Role of educational programs in management of patients with medication-overuse headache

Patients with primary headaches are prone to frequent uncontrolled use of analgesics, leading to medication-overuse headache (MOH). One of the most accessible and effective strategies for its prevention is informing patients about the potential danger of its development. For this, training programs («schools») are conducted.Objective: to evaluate the effectiveness of educational programs in management of patients with MOH and its prevention.Patients and methods. We included 120 patients (12 men and 108 women, mean age: men – 46.3±3.54 years, women – 41.3±9.5 years) with primary headache and MOH. The follow-up period was 12 months. First, patients were divided into two groups depending on the clinical diagnosis: group I (n=44) – patients with chronic primary headaches without MOH, group II (n=76) – patients with chronic primary headaches and MOH. Then, patients in each group were randomized into subgroups depending on the prescribed therapy. All participants underwent repeated clinical examinations and questionnaires assessment at 1-, 3- and 12-months follow-ups. In addition, all patients kept a headache diary. An educational «school» developed for this study was held in those subgroups where educational programs were specified.Results and discussion. We observed a significant decrease in mean Headache-Attributed Lost Time (HALT) and Headache Impact Test (HIT-6) scores (р<0,05) at 12-months follow-up in subgroups where headache educational programs were combined with drug therapy, compared to the subgroups without educational programs. At the end of follow-up, we found a mean 1.75-fold increase in patients' treatment satisfaction (compared to baseline) in the subgroups where the «school» was held. Financial costs during the 12-month follow-up period for patients decreased by seven times because most patients stopped taking medications to relieve headaches.Conclusion. Information and educational programs are an integral part of the management of patients with MOH.

Association between diet and migraine characteristics: The role of Dietary Inflammatory Index

Background: Migraine is a neurologic disorder. Although, based on previous evidence, migraine is related with inflammation and oxidative stress, its relationship with the inflammatory potential of the diet is still unknown. Thus, the aim of this study was to show the correlation between Dietary Inflammatory Index (DII) and severity and duration of migraine headache. Methods: In this cross-sectional study, 266 women who suffered from migraine, were included. Demographic and anthropometric data were collected form all participants. 147-item semiquantitative food frequency questionnaire (FFQ) was collected to assess dietary intake and consequently, DII scores were calculated. Migraine Disability Assessment (MIDAS) questionnaire, Visual Analog Scale (VAS), and a 30-day headache diary were also completed by each participant. Results: The DII score ranged between -4.22 and 5.19 and its median [interquartile range (IQR)] was 0.003 (-1.48-1.55). There was no meaningful association between age, occupation, physical activity (PA), weight, height, Body Mass Index (BMI), waist circumference (WC), hip circumference, waist-to-hip ratio (WHR) and DII score classifications (P > 0.050). Subjects with more than 20 days of headache had higher DII score compared to those with less than 10 days per month [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.12-2.08, P = 0.001]. There was no association between DII and migraine severity (VAS and MIDAS) in the crude and adjusted model of logistic regression. Although there was a significant association between headache duration and DII (P = 0.020), this relationship was not meaningful after adjusting for age, PA, BMI, and job status (OR = 0.53, 95% CI = 0.28-1.00, P = 0.052). Conclusion: The present study showed a direct association between headache frequency and DII. Nevertheless, any relationship was not found between headache duration or migraine severity and DII score. Future large and prospective studies are needed to explore the effect of inflammatory potential of diet in migraine characteristics.

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

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 (<i>P</i>&lt;.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.