Longitudinal determinants of employment status in people with relapsing-remitting multiple sclerosis.

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS). Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status. Results: People with a deteriorated employment status after three years reported more depression (p=0.009), a higher impact of fatigue (p<0.001), more cognitive complaints (p<0.001) and less workplace support (p=0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status. Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status.

Development of an international, multidisciplinary, patient-centered Standard Outcome Set for Multiple Sclerosis: The S.O.S.MS project.

BACKGROUND: Currently, outcomes of Multiple Sclerosis (MS) are not standardized and it is unclear which outcomes matter most to people living with MS. A consensus between patients and healthcare professionals on which outcomes to measure and how, would facilitate a move towards value-based MS care. OBJECTIVE: to develop an internationally accepted, patient-relevant Standard Outcome Set for MS (S.O.S.MS). METHODS: A mixed-method design was used, including a systematic literature review, four patient focus groups (n=30) and a RAND-modified Delphi process with seventeen MS experts of five disciplines from seven countries (the Netherlands, United States of America, Portugal, Ireland, India, New Zealand, Switzerland and Turkey). RESULTS: A standard outcome set for MS was defined, consisting of fourteen outcomes divided in four domains: disease activity (n=3), symptoms (n=4), functional status (n=6), and quality of life (n=1). For each outcome, an outcome measure was selected and the measurement protocol was defined. In addition, seven case-mix variables were selected. CONCLUSION: This standard outcome set provides a guideline for measuring outcomes of MS in clinical practice and research. Using this set to monitor and (inter)nationally benchmark real-world outcomes of MS can support improvement of patient value and ultimately guide the transition towards value-based MS care.

Subjective cognitive impairment is related to work status in people with multiple sclerosis.

Background: Unemployment is common among people with multiple sclerosis (pwMS) and has been associated with subjective cognitive difficulties, specifically in memory, attention, and executive functioning. However, longitudinal research on subjective cognitive difficulties and employment is scarce. Objective: We investigated whether subjective cognitive impairment (SCI), based on the clinical cut-off score of the MS Neuropsychological Screening Questionnaire (MSNQ), was associated with work status and negative work events (NWE) at baseline and after 2 years. Moreover, we investigated whether four MSNQ subdomains were related to work status and NWE. Methods: 287 participants (77.4% female, median age = 42 years) completed questionnaires on subjective cognitive functioning, depression, anxiety, and fatigue, and completed the Symbol Digit Modalities Test (SDMT). After baseline comparisons, logistic regression analyses were performed, with work status and NWE at baseline, and employment change and NWE change within 2 years after baseline as dependent variables. Independent variables included SCI and the MSNQ domains. Covariates anxiety, depression, fatigue, and SDMT were added. Results: SCI, depression and anxiety were associated with work status (Nagelkerke R 2 = .286), but only SCI was associated with employment change (Nagelkerke R 2 = .164). No predictors were associated with NWE at baseline or follow-up. In addition, no MSNQ subdomain was related to work status, employment change or NWE. Conclusion: Unemployed pwMS and pwMS with a deteriorated work status reported more cognitive difficulties after 2 years than employed pwMS or pwMS with a stable work status. In addition, depression, and anxiety were associated with work status.

Self-reported occupational functioning in persons with relapsing-remitting multiple sclerosis: Does personality matter?

BACKGROUND: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS. METHODS: 241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates. RESULTS: Personality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R2 = 0.13) and considering to reduce work hours (R2 = 0.12). A higher impact of fatigue (B = -0.05, p = .008, ß = 0.46, p = .001 and ß = -0.36, p = .001) was associated with absenteeism from work (R2 = 0.15), more presenteeism (R2 = 0.35) and lower work ability (R2 = 0.25). A higher impact of fatigue (ß = 0.46, p = .001) and anxiety (ß = 0.25, p = .001) were associated with more work difficulties (R2 = 0.54). CONCLUSION: Personality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the models was limited, emphasizing the need to additionally examine other (contextual) factors when considering occupational challenges in MS.

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis.

BACKGROUND: Recently, ocrelizumab (Ocrevus®) was approved for the treatment of primary progressive multiple sclerosis (PPMS) based on data from the ORATORIO clinical trial. Real-world data about the clinical effectiveness of ocrelizumab has yet to be gathered. OBJECTIVE: The aim of this study was to provide data about the clinical effectiveness of ocrelizumab for patients diagnosed with PPMS in a real-world setting. METHODS: We conducted a retrospective cohort study of all patients with PPMS who started ocrelizumab treatment (n = 21) in St. Antonius Hospital (Utrecht/Nieuwegein, the Netherlands) between April 2018 and December 31, 2018. Primary outcome was pre- versus post-ocrelizumab disability worsening rate (from 96 weeks prior to first ocrelizumab administration up to 24 weeks post first ocrelizumab administration). RESULTS: Disability worsening rate while on treatment significantly differed (lower) from disability worsening rate in pre-treatment period (Z = -2.81, p ≤ .01). Three out of 17 patients showed a clinically relevant improvement in disability status after treatment start. CONCLUSION: Ocrelizumab can stabilize disability progression in patients with PPMS. Some patients even showed a clinically relevant improvement in disability status. Further research should help to identify which patients benefit most from ocrelizumab.

Empathy in multiple sclerosis--Correlates with cognitive, psychological and occupational functioning.

BACKGROUND: Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning. METHODS: 278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures. RESULTS: Empathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X2(df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=-0.21, p = 0.001), higher extraversion (r = 0.25, p ≤ 0.001), agreeableness (r = 0.55, p ≤ 0.001) and conscientiousness (r = 0.27, p ≤ 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = -0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = -0.34, p ≤ 0.001), less fatigue (r = -0.37, p ≤ 0.001), higher agreeableness (r = 0.59, p ≤ 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = -0.34, p ≤ 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls. CONCLUSION: Empathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition.

A tumefactive demyelinating lesion in a person with MS after five years of fingolimod.

A 38-year-old man with relapsing remitting multiple sclerosis (RRMS) developed a tumefactive demyelinating lesion (TDL) after being clinically and radiologically stable on fingolimod for the last five years. TDLs in MS tend to occur early on in the disease and are uncommon in longstanding MS. Compared to other immune modifying drugs used in MS, there is a relatively high and still increasing number of reports describing the development of TDL under treatment with fingolimod, suggesting a causal relation.

Caregiver strain among life partners of persons with mild disability due to relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS. OBJECTIVE: The current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS. METHODS: We included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain. RESULTS: 24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (ß = 0.16, p = 0.04), more physical disability (ß = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (ß = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (ß = 0.32, p = 0.001) were associated with higher caregiver strain (R2 = 0.49). CONCLUSION: Higher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS.

Cost-minimization analysis of alemtuzumab compared to fingolimod and natalizumab for the treatment of active relapsing-remitting multiple sclerosis in the Netherlands.

AIM: In active relapsing remitting multiple sclerosis (RRMS) patients requiring second-line treatment, the Dutch National Health Care Institute (ZiN) has not stated a preference for either alemtuzumab, fingolimod, or natalizumab. The aim was to give healthcare decision-makers insight into the differences in cost accumulation over time between alemtuzumab-with a unique, non-continuous treatment schedule-and fingolimod and natalizumab for second-line treatment of active RRMS patients in the Netherlands. METHODS: In line with ZiN's assessment, a cost-minimization analysis was performed from a Dutch healthcare perspective over a 5-year time horizon. Resource use was derived from hospital protocols and summaries of product characteristics, and validated by two MS specialists. Unit costs were based on national tariffs and guidelines. Robustness of the base case results was verified with multiple sensitivity and scenario analyses. RESULTS: Alemtuzumab results in cost savings compared to fingolimod and natalizumab from, respectively, 3.3 and 2.8 years since treatment initiation onwards. At 5 years, total discounted costs per patient of alemtuzumab were €79,717, followed by fingolimod with €110,044 and natalizumab with €122,238, resulting in cost savings of €30,327 and €42,522 for alemtuzumab compared to fingolimod and natalizumab, respectively. Key drivers of the model are drug acquisition costs and the proportions of patients that do not require further alemtuzumab treatment after either two, three, or four courses. LIMITATIONS: No treatment discontinuation and associated switching between treatments were incorporated. Consequences of JC virus seropositivity while continuing natalizumab treatment (e.g. additional monitoring) were omitted from the base case. CONCLUSION: The current cost-minimization analysis demonstrates that, from the Dutch healthcare perspective, treating active RRMS patients with alemtuzumab results in cost savings compared to second-line alternatives fingolimod and natalizumab from ∼3 years since treatment initiation onwards. After 5 years, alemtuzumab's cost savings are estimated at €30k compared to fingolimod and €43k compared to natalizumab.

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis.

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing-remitting multiple sclerosis in The Netherlands.

OBJECTIVE: To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS) in The Netherlands. METHODS: A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained. RESULTS: Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of -€2966 (95% CI: -€4209; -€1801), -€6240 (95% CI: -€8800; -€3879), -€15,328 (95% CI: -€21,539; -€9692), and -€28,287 (95% CI: -€39,661; -€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165-364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs-including aseptic preparation of the natalizumab solution-needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years. LIMITATIONS: Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included. CONCLUSION: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.