The Place of Immune Reconstitution Therapy in the Management of Relapsing Multiple Sclerosis in France: An Expert Consensus.

The treatment strategy in relapsing multiple sclerosis (RMS) is a complex decision requiring individualization of treatment sequences to maximize clinical outcomes. Current local and international guidelines do not provide specific recommendation on the use of immune reconstitution therapy (IRT) as alternative to continuous immunosuppression in the management of RMS. The objective of the program was to provide consensus-based expert opinion on the optimal use of IRT in the management of RMS. A Delphi method was performed from May 2022 to July 2022. Nineteen clinical assertions were developed by a scientific committee and sent to 14 French clinical experts in MS alongside published literature. Two consecutive reproducible anonymous votes were conducted. Consensus on recommendations was achieved when more than 75% of the respondents agreed or disagreed with the clinical assertions. After the second round, consensus was achieved amongst 16 out of 19 propositions: 13 clinical assertions had a 100% consensus, 3 clinical assertions a consensus above 75% and 3 without consensus. Expert-agreed consensus is provided on topics related to the benefit of the early use of IRT from immunological and clinical perspectives, profiles of patients who may benefit most from the IRT strategy (e.g. patients with family planning, patient preference and lifestyle requirements). These French expert consensuses provide up-to-date relevant guidance on the use of IRT in clinical practice. The current program reflects status of knowledge in 2022 and should be updated in timely manner when further clinical data in IRT become available.

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.

Expert opinion: Criteria for second-line treatment failure in patients with multiple sclerosis.

OBJECTIVES: In the management of multiple sclerosis (MS), defining criteria for identification of suboptimal therapy responses and switching treatment is essential to avoid worsening. Despite the lack of a standardised definition, criteria for first-line treatment are well documented in the literature, based on clinical measures or magnetic resonance imaging (MRI) (gadolinium enhancing [Gd+] lesions or new/enlarging T2 lesions) assessed during the first 6-18 months after treatment initiation. However, it is unknown whether the same criteria can be used for second-line treatment failure. METHODS: Five regional boards involving 36 French MS experts were convened to discuss published literature regarding criteria for first- and second-line treatment failure, and to identify differences in local therapeutic practices. A national board of 11 experts was subsequently conducted to identify convergences and differences between regions, and to propose second-line criteria for the definition of therapeutic failure. RESULTS: Published information is lacking regarding second-line treatment failure criteria. In light of this, regional differences in current therapeutic practices are justifiable. Due to the risk-benefit ratio of these treatments and limited options for third-line treatments, the authors recommend a different therapeutic approach when assessing second-line treatment failure. The treatment switch for second-line treatment should be informed by confirmed disease progression, after 6 months, or combined clinical and MRI outcomes, but only after at least 1 year of treatment. CONCLUSIONS: Experts compared therapeutic attitudes and practices regarding second-line treatment failure between French regions. They identified convergences that were used to propose a national agreement on second-line treatment failure criteria, which should be evaluated in real-life prospective cohorts.

Treatment satisfaction and quality of life in patients treated with fingolimod.

BACKGROUND: The development of oral treatments for relapsing-remitting multiple sclerosis (RRMS) may alter patient satisfaction and quality of life (QoL). The aim of this survey was to evaluate treatment satisfaction and QoL in patients treated with fingolimod in everyday clinical practice in France. METHODS: Neurologists treating MS in France were invited to participate in the survey by telephone. Each physician was expected to recruit up to six patients with RRMS currently being treated with fingolimod. Enrolled patients were asked to complete the Treatment Satisfaction Questionnaire for Medication (TSQM), the 3-level 5-dimension EuroQoL instrument, as well as specific questions on change in QoL since starting fingolimod. Factors associated with the TSQM score were evaluated using multiple logistic regression analysis. RESULTS: Two hundred and fourteen patients were recruited by 54 neurologists. The mean age of the patients was 41.6±10.0 years, and 73.4% of them were women. During the hospitalization for initiation of fingolimod treatment, 70.1% of patients had received information on MS, 76.6% had received information on fingolimod, and 20.7% had participated in a therapeutic education program. The two variables with the strongest associations with high TSQM scores (≥75) were a positive perception of initial hospitalization (hazard ratio: 10.27) and receiving information on MS during hospitalization (hazard ratio: 5.70). The mean EQ-visual analog scale score was 71.6±16.8. The mean EQ-visual analog scale score was significantly higher in patients satisfied with their treatment (75.8±15.2) compared to those unsatisfied with treatment (66.6±17.2). The proportion of patients who reported an improvement in their capacity to plan for the future was higher in satisfied (72.6%) than in unsatisfied patients (49.5%). CONCLUSION: The majority of patients treated with fingolimod are satisfied with their treatment. Treatment satisfaction is associated with better self-rated QoL and an improvement of QoL since starting treatment.

Country breakout session highlights.

At the 2016 MS Experts Summit, country-relevant aspects pertaining to the management of symptoms and disability in multiple sclerosis (MS), with emphasis on those associated with spasticity, were explored in interactive country breakout sessions chaired by selected MS experts. Attendees had the opportunity to review and discuss topics in their own native language. After feedback from each session leader, key messages were collated and presented in a Plenary Session by Summit chair, Professor Angelo Ghezzi. Topics at this year's Summit included: gait tracking (Germany/Switzerland); the Care Alliance against MS spasticity (Italy); MS spasticity and associated symptoms (France); improvement in MS symptoms and functionality and patients' independence (Spain); Swedish MS guidelines (Sweden/Rest of World).

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.

Apathy and depression in mild Alzheimer's disease: a cross-sectional study using diagnostic criteria.

Apathy and depression are the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). In a cross-sectional observational study of 734 subjects with probable mild AD, we evaluated the prevalence of apathy and depression. After the use of specific diagnostic criteria, we tested the interaction between the two syndromes and their relation with specific comorbidities, and different functional outcomes. Depression was diagnosed using the diagnostic criteria for depression in AD, and apathy with the diagnostic criteria for apathy in neuropsychiatric disorders. According to the specific diagnostic criteria, depression had a 47.9% prevalence, while apathy prevalence was 41.6%. Apathy and depression were associated in 32.4% of patients (n = 225). 9.4% (n = 65) had only apathy, 15.4% (n = 107) had only depression, and 42.9% had no apathy and no depression (n = 298). The three most frequent depressive symptoms were fatigue or loss of energy (59.4%), decreased positive affect or pleasure in response to social contacts and activities (46.2%), and psychomotor agitation or retardation (36.9%). Concerning apathy, loss of goal-directed cognition was the most frequently altered (63.6%), followed by loss of goal-directed action (60.6%) and loss of goal-directed emotion (43.8%). Patients with both apathy and depression more frequently required a resource allowance for dependency. Neurological comorbidities were more frequent in the "apathy and depression" and "depression alone" groups (p < 0.001). Apathy and depression overlap considerably, and this might be explained by the presence of some non-specific symptoms in both diagnostic criteria. The need for social support is higher when a patient fulfills the two diagnostic criteria.

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter.

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P < 0.0001). Over the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. Although this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.