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.

Anxiety and Coping Strategy Changes in Multiple Sclerosis Patients Initiating Fingolimod: The GRACE Prospective Study.

The objective of this prospective study was to assess the changes in anxiety levels, and their relationship with coping strategies over the first four months of fingolimod treatment in patients with relapsing remitting multiple sclerosis (RRMS). Data were collected at the inclusion visit (Visit 1) and 4 months later (Visit 2). We used the Hospital Anxiety and Depression Scale (HADS) to assess the level of anxiety and the Coping Inventory for Stressful Situations scale to assess the coping strategies used when engaged with stressful situations. The HADS anxiety scores were compared between Visits 1 and 2, according to the preferred coping strategy. At Visit 1, half of the 198 patients included were considered to be anxious (doubtful or in a certain way). The same proportion preferentially used an avoidance-oriented strategy and one-third preferentially used an emotion-oriented strategy. The mean HADS anxiety score decreased significantly (p = 0.001) at Visit 2 (8.1 ± 4.0) compared to Visit 1 (8.8 ± 4.3), particularly in the group of patients who used an emotion-oriented strategy (p = 0.002). In conclusion, the initiation of fingolimod in patients with RRMS is followed by a decrease of anxiety levels which vary according to the coping strategy used.

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.

Reasons for switching to fingolimod in patients relapsing-remitting multiple sclerosis in France: the ESGILE study.

BACKGROUND: Timely treatment switching is an important strategy in optimising management of patients with relapsing remitting multiple sclerosis (RRMS). Patient preferences, as well as clinical benefit, may contribute to the switch decision. Information on reasons determining switching choices and on outcome according to the reason for switching is scarce. Study objectives were to describe the consequences of switching to fingolimod in terms of clinical improvement according to the reasons underlying the switch and to evaluate treatment acceptability from the patient's perspective. METHODS: This prospective observational study was conducted by 71 neurologists in France and included patients with RRMS switching to fingolimod following ≥6 months treatment with a first-line disease modifying treatment (DMT). Reasons for switching were documented. Patients were evaluated at inclusion and 12 months after initiating fingolimod. Physicians documented clinical status by relapse activity, disability (EDSS) at each visit and improvement with the Clinical Global Impression - Change (CGI-C) at Month 12. Patients rated improvement at Month 12 with the Patient Global Impression - Change (PGI-C) and treatment acceptability with the ACCEPT® questionnaire. Adverse events reported during fingolimod treatment were documented. RESULTS: Overall 232 patients were recruited of whom 190 could be analysed. Multiple reasons for switching were frequently given; 113 patients (59.4%) switched from a first-line injectable DMT. Switching was motivated by disease worsening in 161 patients (84.7%), tolerability in 35 (18.4%) and patient preference in 58 (30.5%). During the follow-up period, 38 patients (20.0%) experienced at least one exacerbation. The mean EDSS score was stable (2.0 ± 1.3 at inclusion; 2.0 ± 1.5 at M12). With the CGI-C, 67 patients (38.7%) were considered improved and 23 (13.3%) worsened. Although no obvious differences in CGI-C ratings were observed as a function of the reason for switching, when patient preferences entered into the decision, the proportion of patients considered minimally improved was somewhat higher (37.7%) and the proportion considered unchanged somewhat lower (41.5%). With the PGI-C, more patients rated themselves improved than were rated as improved by the physician: of 64 patients rated as 'no change' on the CGI-C, 21 (32.8%) rated themselves as 'improved' and 10 (15.6%) as 'worsened'. The overall level of agreement between the two measures was moderate (κ = 0.48 [95% CI: 0.35 - 0.60]). The mean general treatment acceptability score on the ACCEPT® questionnaire was 42.7 [95%CI: 34.5 - 50.9] at inclusion (reflecting acceptability of the previous DMT) and 64.6 [95%CI: 57.6 - 71.6] at M12 (reflecting acceptability of fingolimod). Mean dimension scores ranged from 36.7 for effectiveness to 72.2 for medication inconvenience at inclusion and from 63.4 for effectiveness to 96.8 for medication inconvenience at M12. The frequency and nature of reported adverse events was consistent with the well-characterised safety profile of fingolimod. CONCLUSION: Most patients switching from a first DMT to fingolimod do so due to persistent disease activity during the initial treatment, although patient preferences are also important. Switching is followed by a reduction in disease activity, perceived improvement in the clinical state of the patient and improved acceptability of treatment.