Severe migraine and its control: A proposal for definitions and consequences for care.

Currently many patients with severe migraine do not receive appropriate treatment and are never referred to specialist headache centres. On the other hand, specialist headache centres are frequently attended by patients whose migraines could be managed adequately in the community. One reason for this may be the absence of standardised definitions of migraine severity and control and of a treatment algorithm for orientating difficult-to-treat patients to specialist headache centres. Based on a review of the relevant literature and consensus meetings, proposals have been made for these items. We propose that migraine should be considered severe if headache frequency is at least eight migraine days per month or, if headaches are less frequent, the HIT-6 score is ≥60 or ≥50% of headaches require complete interruption of activity. The proposed definition of migraine control is defined on the basis of appropriate response to acute headache therapy and to preventative therapy. A treatment algorithm is proposed to assess migraine control regularly and to adapt therapy accordingly. These proposals may contribute to developing and testing strategies for management of severe disease with appropriate and effective preventive treatment strategies. With the anticipated introduction of new possibilities for migraine prevention in the near future, the time is ripe for a holistic approach to migraine management.

An instrument to assess patient satisfaction with epilepsy treatment.

AIMS: Patient satisfaction with antiepileptic drugs is an important component in the management of epilepsy. This study aimed to develop a visual analog scale (VAS) to evaluate patient satisfaction with the effectiveness and tolerability of the current antiepileptic treatment and to identify the most appropriate threshold scores of patient dissatisfaction predictive of a decision to change the antiepileptic drugs. METHODS: This observational study was conducted among patients with epilepsy consulting a neurologist in France. Two anonymous questionnaires were used, one for patients and one for neurologists. The patients' questionnaire assessed satisfaction using a four-point Likert scale and a 10-centimeter VAS. The neurologists' questionnaire evaluated whether the neurologist decided to change the current treatment or not. The determination of the threshold scores predictive of patient dissatisfaction correlated with a change of the medication was performed using analyses of receiver operating characteristic curves. Visual analogue scale scores collected from the patient questionnaire were tested against the responses collected from the neurologist questionnaire. RESULTS: Five hundred eighteen patient questionnaires and five hundred seven neurologist questionnaires were completed. For the satisfaction with effectiveness and tolerability, the mean VAS scores were 6.7±2.8 and 7.0±2.8, respectively and were, respectively, 6.9±1.7 and 7.0±1.6 for patients who declared to be satisfied with their current antiepileptic drugs and were, respectively, 3.4±1.7 and 3.3±1.9 for those who declared to be dissatisfied. The neurologist decided to change the current antiepileptic drugs in 41.1% (n=208) of the cases principally because of inadequate effectiveness. With respect to the receiver operating characteristic curves, a VAS threshold of 6 would correctly predict the decision to change the current antiepileptic drugs with sensitivity and specificity values over 73% for both effectiveness and tolerability. CONCLUSIONS: The VAS developed in this study can help patients to evaluate their antiepileptic drugs and to facilitate timely treatment modification when the current treatment is unsatisfactory.

Management and monitoring of patients treated with zonisamide: the OZONE study.

AIM: To characterise patients treated with zonisamide in everyday practice and describe the effectiveness and tolerability of treatment. METHODS: This was an observational, longitudinal, naturalistic study, conducted by neurologists in France. Patients who had started zonisamide treatment at least three months prior to inclusion were eligible. Data were collected at routine consultations at inclusion (Visit 1) and three to six months later (Visit 2). At Visit 1, investigators documented epilepsy-related variables based on patient records before initiation of zonisamide and at inclusion. At Visit 2, the investigators re-evaluated seizure activity and rated effectiveness. Adverse events were also documented. RESULTS: A total of 428 patients were included in the study based on evaluation by 132 neurologists. Zonisamide was initiated at a daily dose of 50 mg and 25 mg in 61% and 31.8% of patients, respectively. The median maintenance dose was 300 mg/day. Prior to initiation of zonisamide, the mean seizure frequency was 16.0 seizures/month. This was reduced to 8.7 seizures/month at Visit 1 and to 7.1 seizures/month at Visit 2. The response rate and proportion of seizure-free patients was 61.9 and 31.1% at Visit 1 and 65.9 and 25.6% at Visit 2, respectively. The frequency of seizures at Visit 2 decreased significantly (p<0.05) for all seizure type subgroups, except for simple partial seizures. Responder rates were >60% for all analysed subgroups. The proportion of seizure-free patients was significantly higher in patients receiving bitherapy, compared to the others (p=0.007). The most frequently reported adverse event was somnolence (5.1%); three serious adverse events were reported. CONCLUSION: In everyday practice, zonisamide is principally used in association with other antiepileptic drugs for the treatment of focal epilepsy in adults. It is effective in improving seizure control and quality of life, and is generally well-tolerated.

Stability, responsiveness, and reproducibility of a visual analog scale for treatment satisfaction in migraine.

OBJECTIVES: To evaluate the stability, responsiveness, and reproducibility of a simple visual analog scale (VAS). BACKGROUND: In order to help physicians in the management of migraine in everyday general practice and assess whether the treatments that they are currently prescribing are actually effective, a VAS of treatment satisfaction with acute migraine treatments has been developed. METHODS: The study used an open-label, multicenter, prospective design. Adult patients fulfilling diagnostic criteria for migraine and who consulted a participating hospital or community neurology clinic were eligible. At inclusion, patients rated their satisfaction with their current treatment on the VAS. Those scoring 7-10 (satisfied) on the VAS were allocated to the VASCO cohort, and those scoring 0-4 (dissatisfied) were switched to almotriptan and allocated to the ALMO cohort. Patients scoring between 4 and 7 were assigned to 1 or other cohort at the physician's discretion. The VAS was re-administered at home the next day and also after the treatment of 3 further headaches, both at home and at a follow-up visit. RESULTS: Ninety-eight patients in the VASCO cohort and 102 in the ALMO cohort were analyzed. Stability was evaluated in the VASCO cohort: 55/98 patients initially satisfied with treatment remained so at study end, whereas 7/98 became dissatisfied. Responsiveness of the VAS to a change in treatment was evaluated in the ALMO cohort: 64/102 patients moved to a higher treatment satisfaction category, whereas 6/102 moved to a lower one. Reproducibility of the VAS was determined in 4 settings (both at the inclusion visit and at study closure in both cohorts). In each setting, VAS scores were compared between consultation and at-home ratings. In 3 of the 4 settings (both measures in the ALMO cohort and at study closure in the VASCO cohort), good agreement was observed between the 2 ratings (κ = 0.62-0.69). At inclusion in the VASCO cohort, agreement was only fair (κ = 0.33). CONCLUSIONS: The VAS scale described here is a responsive and easy-to-use tool for evaluating treatment satisfaction and for monitoring changes to treatment if these are required.

Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study.

INTRODUCTION: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS. METHODS: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion. RESULTS: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9). CONCLUSIONS: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis.

Use of antimigraine treatments by general practitioners.

OBJECTIVES: To assess headache treatment patterns in 2 groups: general practitioners (GPs) who suffered from migraine themselves (GP-M) and GPs having a close family member with migraine (GP-CFM). The secondary objective was to assess the impact of migraine on activities of daily living in these 2 groups. BACKGROUND: Personal experience of migraine may influence prescribing practices of physicians treating patients with migraine. Little data are available on perceptions of migraine by GPs. METHODS: This was an observational, cross-sectional, pharmacoepidemiological survey conducted in primary care in France. Most GPs completed 1 of 2 questionnaires, and GPs belonging to both groups could complete both. Data were collected on headache treatments used (GP-M) or prescribed (GP-CFM), and on self-reported (GP-M) or described (GP-CFM) migraine features and impact on daily activities. RESULTS: The most frequently reported acute headache treatments in both groups were triptans and non-steroidal anti-inflammatory drugs (>75% of GPs); >81% of GPs in both groups were satisfied with acute headache treatments. Only 6.9% of the GP-M group used and 17.2% of the GP-CFM group prescribed a prophylactic treatment, which was considered satisfactory by 46.2% and 56.1%, respectively. In the preceding 3 months, 79.4% of the GP-M group reported handicap in daily activities due to migraine, 23.6% interruption of extraprofessional activities and 7.6% interruption of work. In the GP-CFM group, 32.6% described interruption of extraprofessional activities and 57.3% interference with daily activities or work. CONCLUSIONS: Acute headache treatment prescribed by French GPs for their own migraines or those of their relatives respect practice guidelines and is considered as effective and satisfactory. Use of prophylactic medication is low and its effectiveness perceived as limited. Better use of prophylactic treatments may attenuate the impact of migraine on daily activities.

An instrument to assess patient perceptions of satisfaction with acute migraine treatment (EXPERT Study).

OBJECTIVE: The objective of the nationwide EXPERT survey carried out in France in 2005 was to compare satisfaction with treatment with treatment effectiveness in migraine patients consulting general practitioners (GPs) for migraine, and to establish an instrument to easily evaluate the adequacy of acute treatment of migraine. BACKGROUND: Many migraine patients feel satisfied with their current acute treatment of migraine whereas objective evaluation reveals poor treatment effectiveness. METHODS: A total of 2108 GPs included 11,274 migraine patients. Satisfaction with treatment was evaluated using a 4-point verbal scale and a 10-cm visual analog scale (VAS). Treatment effectiveness was assessed by the 4-item questionnaire designed by the French Medico-Economic Evaluation Service (ANAES) and the French Society for the Study of Migraine Headache (SFEMC). RESULTS: In total, 5224 patients (49.8%) stated that they were satisfied with their treatment. Mean VAS score was 5.1. Only 17% of patients (1789/10,539) gave positive responses at the 4 questions of the ANAES/SFEMC questionnaire. VAS score was high for patients satisfied with their treatment and with good treatment effectiveness. Two VAS thresholds were determined using receiver operating characteristic curves that allowed easy identification, with high sensitivity and specificity, of patients satisfied/dissatisfied with their current treatment and with good/poor treatment effectiveness. Based on EXPERT data, this instrument showed that only 16% of patients using triptans (597/3719) were dissatisfied and reported poor treatment effectiveness, whereas treatment was inadequate for 63% of those using aspirin or nonsteroidal anti-inflammatory drugs (1882/2992), 74% of those using paracetamol or other analgesics (2229/2998), and 53% of those using ergotamine (253/474). CONCLUSIONS: The new instrument should allow easy identification in general practice of the patients receiving an effective or ineffective acute treatment of migraine and thus facilitate the implementation of treatment guidelines for migraine.

Migraine and migraines of specialists: perceptions and management.

OBJECTIVES: To describe the perception of migraine by neurologists in France, to compare perceptions between neurologists who did and did not suffer from migraines and to describe treatments used for their own migraines. BACKGROUND: Patients with migraine are usually undertreated, as treatment guidelines are frequently not followed and, therefore, resulting treatment satisfaction is low. One reason for this may be inappropriate perceptions of physicians concerning the seriousness of the pathology and the need to treat. However, available information on physician perceptions of migraine is limited. METHODS: This was an observational, epidemiological survey conducted both in hospital- and community-based neurologists in France. Participating neurologists completed an anonymous questionnaire which collected data on demographics, migraine status, and perceptions of migraine. Neurologists who considered themselves migraineurs also provided data on migraine impact, treatment and on treatment satisfaction. Distributions of responses to questions on migraine perceptions were compared between migraineur and nonmigraineur neurologists. RESULTS: The study included 368 neurologists, of whom 179 (48.6%) were migraineurs themselves. Some 92.3% of participants claimed to be very or quite interested in migraine. Migraine was considered a real illness by 96.5% of neurologists and to be very or quite disabling by 96.6%. Around half perceived migraine as a challenging condition to manage with respect to unrealistic patient expectations (46.2%), time-consuming treatment (48.9%), and complications because of anxious or depressive comorbidity (59.9%) or medical nomadism (consulting multiple physicians for the same condition; 47.0%). No significant differences in any perception items were observed between migraineur and nonmigraineur neurologists. In total, 83.1% of neurologists were satisfied with acute headache treatments and 60.4% with prophylactic headache treatments. The most frequently reported treatments for neurologist's own migraines were nonsteroidal anti-inflammatory drugs (used by 57.0%) and triptans (50.3%). CONCLUSIONS: French neurologists are interested and concerned about migraine but find it challenging to treat. Migraine perceptions do not differ between neurologists who do and do not suffer from migraines themselves. Neurology training needs to prepare medical students adequately for the challenges of migraine treatment in terms of patient communication and psychiatric issues.

Implementation of guidelines for allergic rhinitis in specialist practices. A randomized pragmatic controlled trial.

BACKGROUND: Guidelines for allergic rhinitis are more effective than free-treatment choice in the control of seasonal allergic rhinitis. OBJECTIVE: To validate the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines in the treatment of intermittent and persistent allergic rhinitis induced by pollens. DESIGN: A multicenter, open-label, parallel, pragmatic randomized study compared two therapeutic strategies during a 2-week treatment course. In the first strategy ('guidelines group'), 417 patients were treated according to ARIA with ebastine as oral antihistamine. In the second strategy ('free-choice treatment group'), investigators had a free choice for the treatment of 422 patients. MAIN OUTCOME MEASURES: Quality of life measured using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), work productivity and daily symptom medication scores. RESULTS: 94.2% patients returned the baseline visit questionnaires and 88.6% returned the posttreatment period questionnaires. RQLQ scores were similar in the two groups at baseline. After treatment, there were improvements in the overall score and in all domains in both treatment groups. According to pragmatic methodology, the improvements show that the guidelines group (-1.70 +/- 1.20) is more effective than the free-choice treatment group (-1.52 +/- 1.22) with a gamma risk of 2%. Individual RQLQ scores, work productivity, and daily symptom scores were significantly improved in the guidelines group by comparison to the free-choice treatment group. CONCLUSION: A treatment based on ARIA guidelines offers patients a significant improvement in comparison to the use of a nonstandardized treatment regimen.

Use and overuse of antimigraine drugs by pharmacy personnel in France: COTA survey.

BACKGROUND: Pharmacy personnel are supposed to be well informed of recommendations for proper migraine management, but their easy access to medicines may favor self-medication and promote medication overuse for those with frequent migraine attacks. OBJECTIVE: The main objective of the COTA survey was to investigate migraine management by pharmacy personnel who considered themselves as migraineurs. METHODS: Out of 22,000 pharmacies currently open in France, a questionnaire was proposed to a random sample of approximately 4000 pharmacies with at least 1 self-considered migraineur in the pharmacy staff who accepted to complete and return the questionnaire. The reality of migraine was assessed by the study questionnaire according to the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria. In addition, the study questionnaire inquired about subjects' demographics, headache characteristics, consumption of medications for headaches, subjects' satisfaction with the usual treatment of headaches and treatment effectiveness. Medication overuse was defined in terms of treatment days per month during the previous 3 months according to the ICHD-II criteria for medication overuse headache. RESULTS: Some 74% of the 3326 participating pharmacies with a self-considered migraine subject among their staff actually returned the survey questionnaire. Using the ICHD-II criteria, migraine was confirmed in 85% of participating subjects, of whom 38% were under medical supervision and had asked for a prescription, and 27% used recommended medications. The treatment used was truly effective for only 31% of migraineurs. Medication overuse was observed in 21% of all participating subjects, mostly migraineurs. Most migraineurs with medication overuse (81%) used nonrecommended treatments. CONCLUSIONS: Considering their pivotal role in advising migraine patients who seek their help with self-management, migraine education of pharmacy personnel about proper migraine management should be reinforced.

Migraine burden and costs in France: a nationwide claims database analysis of triptan users.

Objectives: To estimate the burden of migraine in the population of French patients identified as specific migraine acute treatment users compared to a control group. Methods: A cross-sectional retrospective analysis was performed on the Echantillon Généraliste des Bénéficiaires claims database, a 1/97 random sample of the French public insurance database. A representative sample of all adults with at least one delivery of triptans, ergot derivatives or acetylsalicylic acid/metoclopramide (all drugs with a specific label in migraine acute treatment - SMAT) in 2014 was selected with a control group matched on age, gender and geographic region. Among triptan users, a sub-group of over-users was defined according to their level of triptan uptake expressed in defined daily doses (DDD - a standard daily dose of treatment of acute migraine) per month over 3 months and more, was also compared with controls. The cost analysis was performed in a societal perspective for direct costs. Sick leave indirect costs were estimated using the human capital approach. Results: In total 8639 SMAT users (mean age: 44.6 years; 78.7% women) were selected representing a crude prevalence rate of 1.7%. The annual per capita total healthcare expenditures were higher by €280 in this group compared to controls (€2463 vs. €2183). Triptans contributed 47.8% to this extra cost. They used significantly (p < .0001) more frequently than controls antidepressants (20.8% vs. 11.0%), anxiolytics (29.4% vs. 18.8%) and analgesics (53.8% vs. 35.8%). The per capita annual productivity loss associated with sick leave was higher by €295 (€1712 vs. €1417). Among triptan users, there were 2.9% over-users. This last group was characterized by substantially higher per capita annual extra direct (+ €1805) and indirect costs (productivity loss +€706) compared to controls. Conclusions: Due to its high prevalence, migraine costs generate a significant societal burden. The group of over-users concentrates high per capita direct and indirect costs.

Evaluation of French-language internet sites dealing with multiple sclerosis.

BACKGROUND: Information available on the internet has changed patient-neurologist relationships. Its evaluation for multiple sclerosis is only partial, regardless of the language used. OBJECTIVE: We aim to evaluate the content quality and ranking indexes of French-language sites dealing with multiple sclerosis. METHODS: Two French terms and three search engines were used to identify the sites whose ranking indexes were calculated according to their positions on each page designated by the search engines. Three evaluators used the DISCERN questionnaire to assess the content quality of the 25 selected sites. The sites were classified according to the mean of the evaluators' grades. Grading agreement between evaluators was calculated. Ranking indexes were computed as a rank/100. RESULTS: Content level was deemed mediocre, with poor referencing of the information provided. The naïve and two expert evaluators' grades differed. Content quality disparity was found within the different website categories, except for institutional sites. No correlation was found between content quality and ranking index. CONCLUSION: The information available was heterogeneous. Physicians should guide patients in their internet searches for information so that they can benefit from good-quality input which is potentially able to improve their management.

Evaluation of efficacy, tolerability, and treatment satisfaction with almotriptan in 3 consecutive migraine attacks. The migraine--satisfaction with treatment: reality with Almogran study.

The objective of the open-label, multicenter Migraine--Satisfaction with Treatment: Reality with Almogran study was to assess efficacy, tolerability, and satisfaction with almotriptan 12.5 mg among migraineurs who were not achieving adequate results with their current acute therapy. Data from 434 patients (342 evaluable), were obtained for 929 attacks by 154 neurologists in France. Using a questionnaire developed by the National Agency for Accreditation and Evaluation in Health (ANAES), almotriptan was associated with an increased proportion of patients experiencing significant relief at 2 h (69.3 vs. 26.6%), tolerating the medication well (91.2 vs. 76.0%), able to resume activities (70.5 vs. 24.9%), and taking only 1 dose (59.4 vs. 28.1%) compared with previous therapies. At 2 h, headache pain had disappeared in 33.4% of attacks and was mild in 26.9%. Recurrence rate was 28.4% and rescue analgesics were used in 20.9% of attacks. The rate of adverse event-related discontinuations was 2.6%. The proportion of patients who were very satisfied/satisfied overall with almotriptan treatment was 69%. Almotriptan 12.5 mg was effective, well-tolerated and associated with a high rate of treatment satisfaction in patients whose previous acute migraine therapy was inadequate according to the ANAES recommendations.

Severity and impairment of allergic rhinitis in patients consulting in primary care.

BACKGROUND: Allergic rhinitis is a disease impairing quality of life, sleep, and work. A new classification for allergic rhinitis, Allergic Rhinitis and its Impact on Asthma (ARIA), has recently been proposed. OBJECTIVE: To study the effect of allergic rhinitis using ARIA definitions to determine severity and duration. METHODS: A total of 3052 patients consulting general practitioners for allergic rhinitis were studied. Patients were classified according to the 4 classes of ARIA. In all patients, quality of life (Rhinoconjunctivitis Quality-of-Life Questionnaire), sleep (Jenkins questionnaire), and work performance (Allergy-Specific Work Productivity and Activity Impairment questionnaire) were assessed. RESULTS: Mild intermittent rhinitis was diagnosed in 11% of the patients, mild persistent rhinitis in 8%, moderate/severe intermittent rhinitis in 35%, and moderate/severe persistent rhinitis in 46%. The severity of rhinitis has more of an effect on quality of life, sleep, daily activities, and work performance than the duration of rhinitis. In moderate/severe rhinitis, more than 80% of patients report impaired activities, as opposed to only 40% with mild rhinitis. CONCLUSION: It seems that the term moderate/severe should be replaced by severe. A study in the general population is necessary, however, to assess the prevalence of the 4 ARIA classes of allergic rhinitis, especially in patients who are not consulting physicians for their symptoms.