Background. Central sensitization (CS) is the mechanism underlying chronic migraine and other conditions combined into a group of central sensitivity syndromes. The most reliable method for assessing the severity of CS is Central Sensitization Inventory (CSI).Aim. The aim of our study is the evaluation of anti-CGRP monoclonal antibodies (erenumab, fremanezumab) effect on the central sensitization level in migraine patients.Material and methods. We recruited 90 patients over 18 years old diagnosed with episodic migraine (EM) and chronic migraine (CM) according to the International Classification of Headache Disorders, 3rd edition. All patients were from November 2020 to March 2022. Demographic data, history of migraine and previous migraine treatment were collected for each patient. All patients filled out CSI. Dynamics was followed up monthly with headache diaries.Results. After six months of treatment the level of CS in the CM group significantly decreased from the initial level of 41 (32.0, 50.5) to 36 (25.0, 39.0), which corresponds to the absence of clinically significant CS, p = 0.02*. The analysis of points of the CSI after 3 months of treatment shows a significant decrease in the prevalence of pain syndromes, cognitive impairment, asthenic disorders, hypersensitivity and affective disorders.Conclusions. The use of erenumab and fremanezumab is advisable in patients with migraine and comorbid conditions based on the CS mechanism.

Migraine is a chronic neurological disorder that is associated with considerable disadaptive effect on patients. Despite the development of pharmacotherapy strategies for migraine, only one third of patients are satisfied with their overall treatment. Many migraine patients turn to complementary and alternative medicine (CAM), which is not usually considered a part of conventional medicine and is not always evidence-based. In practise, however, they are often used to improve the effectiveness of standard therapy or to provide alternative treatment. In addition, in CAM methods, the patient is actively involved in the choice of treatment strategies, and they have good adherence. The basic principles and approaches of CAM are increasingly being introduced into clinical practise. This review discusses the principles of CAM in the treatment of migraine as a holistic approach using lifestyle strategies and selected non-pharmacological treatments that have been shown to be effective and rational.

Background. Migraine is the second most incapacitating disease and is accompanied by multiple comorbidities, especially in chronic migraines. Migraine treatment and improvement of the patients’ quality of life are an important clinical issue. The calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are the first target therapy for migraine. To date, there are no published data on the duration of effect after using mAbs. Aim. To determine the effect duration after cessation of erenumab treatment in patients with migraine. Methods. The study included 64 patients with migraine, who received at least three doses of erenumab; treatment was stopped when reduction of the headache frequency by at least 30% was achieved. The frequency of headache and migraine were assessed 1, 3 and 6 months after the end of treatment. Results. There was a significant increase in the frequency of headache compared to the values reported at the end of treatment, however, the rates were still significantly lower compared to the baseline values. In some patients, no increase in headache frequency following discontinuation of treatment was observed.

Triptans are a targeted therapy for acute migraine attacks. They are recommended for the treatment of severe attacks when non-specific analgesics are not effective. Four of the seven known triptans with different efficacy and individual tolerability are registered in the Russian Federation. Objective: to determine in an open-label non-comparative single center study efficacy and safety of the new Russian generic tableted rizatriptan 10 mg (Relonova) in real-life clinical practice. Material and methods. Thirty individuals with migraine took part in the study. Patients took rizatriptan to relieve 4 migraine attacks and filled out self-observation diaries and HIT-6 questionnaire before and after therapy. Results. The study involved 30 patients (26 women and 4 men) with mean age of 38.7 ± 9.3 years. Duration of migraine was 19.6 ± 11.4 years, mean number of days with migraine per month was 9.5 [5.25; 16.75]. Most patients (67 %) suffered from episodic migraine and 33 % from chronic migraine; 6 patients (20 %) had migraine attacks with aura; 20 individuals (67 %) received preventive therapy. After taking Relonova medication, pain relief was observed in 86 % of attacks, and in 45 % of cases pain disappeared completely; after 24 hours, pain relief was observed in 87 % of cases, and in 68 % – absence of attacks. A significant decrease in headache intensity was observed within 30 minutes after taking the first dose; in 34 % of attacks the headache returned. Additional analgesic treatment was required in 39 % of cases. Adverse events were observed in 25 % of attacks and were mild. The majority (63 %) of the participants were able to successfully terminate 3 attacks and were responders. Conclusion. Relonova is an effective and safe medication for the relief of migraine attacks.

Aim: to assess the efficacy and safety of the new Russian generic rizatriptan 10 mg tablet in alleviating migraine episodes in a real clinical practice. Patients and Methods: an open-label comparative study was conducted involving 30 patients diagnosed with migraine. Each participant was instructed to treat four migraine episodes (totaling 120 seizures) using rizatriptan 10 mg, administered at the onset of a headache, and to maintain self-monitoring diaries. If the headache recurred after initial relief, but not sooner than two hours after the first dose, a second tablet was advised. In cases where rizatriptan provided insufficient analgesic effect, the use of common analgesics was permitted. The study focused on evaluating both the drug's efficacy and safety profiles. Results: a total of 102 migraine episodes were successfully treated, while some patients opted out due to perceived insufficient efficacy. Pain relief or reduction was reported in 86% of episodes two hours post-dose, and in 87% after 24 hours. Complete pain absence was noted in 45% of episodes two hours after drug administration, and in 68% after 24 hours. A response rate was observed in 63% of participants. Non-responders, identified as those showing no improvement in at least three episodes, exhibited more severe associated symptoms such as photophobia and phonophobia, and a marked increase in headache intensity following physical activity. Mild adverse events were reported in 25% of the episodes, resolving spontaneously without the need for additional therapy. Conclusion: the Russian generic rizatriptan 10 mg tablet was demonstrated to be an effective and safe treatment option for mitigating migraine episodes. KEYWORDS: headache, migraine, triptans, relief of migraine episode, rizatriptan, real clinical practice. FOR CITATION: Filatova E.G., Latysheva N.V., Kadymova N.B., Berdnikova A.V. Relonova in the relief of migraine episodes. Russian Medical Inquiry. 2024;8(10):560–567 (in Russ.). DOI: 10.32364/2587-6821-2024-8-10-3

Small molecule calcitonin gene-related peptide (CGRP) receptor antagonists are commonly referred to as gepants. The first generation of gepants provided the first line of evidence of CGRP-mediated antimigraine medication in 2004-2011. However, further development was halted due to either lack of oral availability or concerns of hepatotoxicity. More than 15 years later, the first second generation of gepants, ubrogepant and rimegepant, are now approved for the acute treatment of migraine with or without aura. Furthermore, a novel and promising third-generation gepant, zavegepant, has recently been approved as well. In this chapter, we review the evidence supporting the effectiveness, safety, and tolerability of gepants for the acute treatment of migraine. Furthermore, we discuss the potential limitations and future directions of this class of migraine-specific medication.

Background. Headache and orofacial pain (OFP) are widespread at specialized pain centers. However, reliable data on their prevalence and co-occurrence are lacking, and prevalence of OFP in headache patients seems to be underestimated. The aim of this study was to evaluate the types of headache in patients with OFP and types of OFP in patients with headache. Methods. We enrolled patients presenting with headache and/or OFP. Patients were examined by an experienced headache and pain specialist who questioned the patients about the presence of OFP. Depression was assessed with the Beck Depression Inventory (BDI-II), anxiety – with the Beck Anxiety Inventory (BAI). Bruxism was evaluated based on subject self-report. Results. We recruited 310 patients: 177 (57%) patients with headache, 28 (9%) patients with OFP and 105 (34%) patients presenting with both types of pain. The prevalence of OFP in headache patients was 37.2%. Migraine was the most prevalent type of headache, while painful temporomandibular disorder (TMD) – the most prevalent form of OFP. Patients with PFP presented with a high prevalence of sleep and awake bruxism. Conclusion. Migraine and pain-related TMD are the most prevalent diagnoses in a specialized pain center. OKI and OKI ACT are soluble forms of ketoprofen and reach peak concentration in 15 minutes. This enables faster onset of action compared to conventional NSAIDs and better tolerability. OKI and OKI ACT are recommended in the acute treatment of migraine with comorbid painful TMD.

OBJECTIVE:To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO).MATERIAL AND METHODS:In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures.RESULTS:Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050).CONCLUSION:The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

On December 24, 2022, in Moscow an interdisciplinary Council of Headache Experts, held under the auspice of the interregional public organization “Russian Society for the Study of Headache”, discussed the key problems of effective treatment of a migraine attack and the possibilities of a specific drug Kaporiza® (rizatriptan). Despite the development of strategies for the relief of migraine attacks and the effectiveness of triptans as first-line therapy, the choice of a specific drug in accordance with the individual clinical profile of the patient is difficult due to the existence of drugs in various forms (standard tablets, oral dispersible forms, injections, nasal sprays, rectal suppositories). Rizatriptan in the form of an orally dispersible tablet (ODT) has a number of advantages: high bioavailability, fast onset of action, and ease of use. Therefore, Kaporiza® (rizatriptan ODT) may be recommended as a priority therapy for all migraine patients who prefer the dispersible tablet form and who experience symptoms of nausea and vomiting, as well as for patients who have experience of poor efficacy and/or poor tolerability of other triptans. The Expert Council recommends to include rizatriptan ODT in the next edition of the clinical guidelines for the diagnosis and treatment of migraine as a first-line agent with Level A evidence.

Background. Menstrual related migraine (MRM) occurs in 60% of women with migraine. These attacks are characterized by high intensity and poor response to abortive and prophylactic treatment. Hormonal therapy is one of the main treatment methods, but it has a large number of limitations. Increase in the CGRP level triggered by a decrease of estrogen levels is one of the basic mechanisms of MRM. It is of interest therefore to study the impact of anti-CGRP monoclonal antibodies (mAbs) in MRM. In addition, many patients have severe pelvic pain in the perimenstrual period (algodysmenorrhea). Algodysmenorrhea is associated with other chronic pain syndromes including migraine. Therefore, it is interesting to study the impact of anti-CGRP monoclonal antibodies on algodysmenorrhea. Material and methods. We recruited 64 women with migraine (episodic and chronic) over 18 years of age with regular menstrual cycle. 21 patients were diagnosed with MRM according to the International Classification of Headache Disorders, 3rd edition. Demographic data, migraine history, menstrual cycle characteristics and algodysmenorrhea symptoms were collected. Patients were treated with erenumab or fremanezumab for 3 months and followed up monthly with headache diaries. Results. After 3 months of treatment, the intensity of menstrual migraine attacks and algodysmenorrhea decreased by 50% or more (p=0,03* and p=0,045*, accordingly). There was a significant decrease in the total amount of headache days in MRM patients.

OBJECTIVE:To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM).MATERIAL AND METHODS:The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score.RESULTS:Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified.CONCLUSION:The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

This consensus reviewed the main current issues of clinical application and integration into everyday practice of a new targeted preventive therapy for migraine using monoclonal antibodies (mAbs) to the calcitonin gene related peptide (CGRP) ligand or receptor. These recommendations are based on current scientific and clinical studies and an analysis of the results of several years of clinical use. The main purpose of the consensus is to assist practitioners in prescribing effective prophylactic treatment of migraine using anti-CGRP mAbs and to improve care for patients with various forms of the disease.

The identification of patients who can benefit the most from the available preventive treatments is important in chronic migraine. We explored the rate of excellent responders to onabotulinumtoxinA in a multicenter European study and explored the predictors of such response, according to different definitions. A pooled analysis on chronic migraineurs treated with onabotulinumtoxinA and followed-up for, at least, 9 months was performed. Excellent responders were defined either as patients with a ≥75% decrease in monthly headache days (percent-based excellent responders) or as patients with <4 monthly headache days (frequency-based excellent responders). The characteristics of excellent responders at the baseline were compared with the ones of patients with a <30% decrease in monthly headache days. Percent-based excellent responders represented about 10% of the sample, whilst frequency-based excellent responders were about 5% of the sample. Compared with non-responders, percent-based excellent responders had a higher prevalence of medication overuse and a higher excellent response rate even after the 1st and the 2nd injection. Females were less like to be frequency-based excellent responders. Chronic migraine sufferers without medication overuse and of female sex may find fewer benefits with onabotulinumtoxinA. Additionally, the excellent response status is identifiable after the first cycle.

Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1–3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

ЦЕЛЬ ИССЛЕДОВАНИЯ Валидизация опросника для оценки центральной сенситизации (ОЦС) при неспецифической боли в шее, сочетающейся с головными болями, — мигренью, головной болью напряжения и цервикогенной головной болью. МАТЕРИАЛ И МЕТОДЫ С участием 37 пациентов с неспецифической болью в шее и 167 пациентов с болью в шее, сочетающейся с эпизодическими и хроническими головными болями, — мигренью и головной болью напряжения, проведена оценка психометрических свойств русскоязычной версии ОЦС, таких как конструктная валидность, конвергентная валидность, надежность «тест — ретест». Проведен факторный анализ ОЦС. РЕЗУЛЬТАТЫ Валидизированная версия обладает хорошей внутренней согласованностью (α Кронбаха = 0,88) и надежностью «тест — ретест» (коэффициент внутриклассовой корреляции ICC2,1 для абсолютного согласия = 0,91). Коэффициент корреляции r Спирмена при оценке корреляции ОЦС с Госпитальной шкалой тревоги и депрессии: для субшкалы «Тревога» r=0,57, для субшкалы «Депрессия» rS=0,56 при p<0,05. Факторный анализ выявил однофакторную структуру опросника. «Эффектов пола и потолка» выявлено не было. Разница между группами «боль в шее» (32 балла) и «боль в шее, сопровождающаяся хроническими головными болями» (45 баллов) составила по ОЦС 13 баллов. Минимальные клинически значимые изменения составили 10 баллов. ВЫВОД В группе пациентов с неспецифической болью в шее, сочетающейся с эпизодическими и хроническими головными болями, валидизированная русскоязычная версия ОЦС обладает хорошими психометрическими свойствами. Необходимы дальнейшие исследования для оценки других психометрических свойств опросника.

The Russian experts’ guidelines on evaluation and treatment of medication-overuse headache are based on evidence-based medicine, the latest revision of the International Classification of Headache Disorders. Basic information about epidemiology, risk factors, pathophysiological mechanisms, evaluation, and the most effective pharmacological drug and non-pharmacological approaches to managing patients with medication-overuse headache are presented.

Background Monoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab. Methods ESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women. Results Out of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs. Conclusions The present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.

Anti-CGRP monoclonal antibodies and particularly Erenumab become the first migraine-specific treatment and have demonstrated high efficacy and safety in the randomized clinical trials.Aim. The aim of this study is the prospective evaluation of the efficacy and safety of Erenumab in patients with episodic migraine (EM) and chronic migraine (CM).Material and мethods. We recruited patients aged 18–85 diagnosed with EM and CM according to the International Classification of Headache Disorders, 3rd edition. All patients were from November 2020 to December 2021. Demographic data, history of migraine and previous migraine treatment were collected for each patient. All patients filled out scales and questionnaires, headache frequency dynamics was followed up monthly with headache diaries.Results. After three months of treatment reduction marked reduction of headache frequency was observed, and 53.5% of patients became ≥ 50% responders. After six months of treatment a further increase in the effect was observed: 57% of patients had at least a two-fold reduction in headache frequency, 74% of patients became ≥ 30% responders. Constipation was observed in 3.8% of patients.Conclusion. Erenumab is safe and effective in the treatment of moderate- and high-frequency EM, CM and medication-overuse headache.