Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting.

BACKGROUND: Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting. METHODS: A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios. CONCLUSIONS: MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.

The association of comorbidities with sleep quality among Australians with multiple sclerosis: Insights from the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND: Comorbidities and poor sleep quality are prevalent among individuals with multiple sclerosis (MS). Our understanding of the effects of comorbidities on sleep quality in MS remains limited. OBJECTIVES: The objectives were to investigate whether the number and presence of specific comorbidities have associations with sleep quality and to assess the relative contribution of comorbidity groups to sleep quality. METHODS: We collected data on sleep quality (using Pittsburgh Sleep Quality Index (PSQI)) and presence of comorbidities in people with MS (n = 1597). Associations between comorbidities and sleep quality were examined using linear regression and dominance analysis. RESULTS: Having more comorbidities was associated with poorer sleep quality (p for trend < 0.001). All 13 groups of comorbidities explained 12.9% of the variance in PSQI from which half of the variance was contributed by mental health disorders. In total, 16 of the 28 comorbidities were associated with significantly worse sleep quality, with the strongest associations seen for 'other autoimmune diseases' (ß = 1.98), depression (ß = 1.76), anxiety (ß = 1.72) and rheumatoid arthritis (ß = 1.62). CONCLUSIONS: Many individual comorbidities are associated with poorer sleep quality, with mental health disorders making the largest relative contribution. Optimal management of comorbidities that make the greatest contributions could have the largest benefit for improving sleep in MS.

Introducing a core dataset for real-world data in multiple sclerosis registries and cohorts: Recommendations from a global task force.

BACKGROUND: As of September 2022, there was no globally recommended set of core data elements for use in multiple sclerosis (MS) healthcare and research. As a result, data harmonisation across observational data sources and scientific collaboration is limited. OBJECTIVES: To define and agree upon a core dataset for real-world data (RWD) in MS from observational registries and cohorts. METHODS: A three-phase process approach was conducted combining a landscaping exercise with dedicated discussions within a global multi-stakeholder task force consisting of 20 experts in the field of MS and its RWD to define the Core Dataset. RESULTS: A core dataset for MS consisting of 44 variables in eight categories was translated into a data dictionary that has been published and disseminated for emerging and existing registries and cohorts to use. Categories include variables on demographics and comorbidities (patient-specific data), disease history, disease status, relapses, magnetic resonance imaging (MRI) and treatment data (disease-specific data). CONCLUSION: The MS Data Alliance Core Dataset guides emerging registries in their dataset definitions and speeds up and supports harmonisation across registries and initiatives. The straight-forward, time-efficient process using a dedicated global multi-stakeholder task force has proven to be effective to define a concise core dataset.

Changes in employment status over time in multiple sclerosis following a first episode of central nervous system demyelination, a Markov multistate model study.

BACKGROUND AND PURPOSE: Understanding predictors of changes in employment status among people living with multiple sclerosis (MS) can assist health care providers to develop appropriate work retention/rehabilitation programs. We aimed to model longitudinal transitions of employment status in MS and estimate the probabilities of retaining employment status or losing or gaining employment over time in individuals with a first clinical diagnosis of central nervous system demyelination (FCD). METHODS: This prospective cohort study comprised adults (aged 18-59 years) diagnosed with FCD (n = 237) who were followed for more than 11 years. At each review, participants were assigned to one of three states: unemployed, part-time, or full-time employed. A Markov multistate model was used to examine the rate of state-to-state transitions. RESULTS: At the time of FCD, participants with full-time employment had an 89% chance of being in the same state over a 1-year period, but this decreased to 42% over the 10-year follow-up period. For unemployed participants, there was a 92% likelihood of remaining unemployed after 1 year, but this probability decreased to 53% over 10 years. Females, those who progressed to clinically definite MS, those with a higher relapse count, and those with a greater level of disability were at increased risk of transitioning to a deteriorated employment state. In addition, those who experienced clinically significant fatigue over the follow-up period were less likely to gain employment after being unemployed. CONCLUSIONS: In our FCD cohort, we found a considerable rate of employment transition during the early years post-diagnosis. Over more than a decade of follow-up post-FCD, we found that females and individuals with a greater disability and a higher relapse count are at higher risk of losing employment.

The quality of life impact of the COVID-19 pandemic and lockdowns for people living with multiple sclerosis (MS): evidence from the Australian MS Longitudinal Study.

PURPOSE: People living with multiple sclerosis (PwMS) in metropolitan Victoria, Australia, experienced a 112-day, COVID-19-related lockdown in mid-2020. Contemporaneously, Australian PwMS elsewhere experienced minimal restrictions, resulting in a natural experiment. This study investigated the relationships between lockdowns, COVID-19-related adversity, and health-related quality of life (HRQoL). It also generated health state utilities (HSU) representative of changes in HRQoL. METHODS: Data were extracted from Australian MS Longitudinal Study surveys, which included the Assessment of Quality of Life-Eight Dimensions (AQoL-8D) instrument and a COVID-19 questionnaire. This COVID-19 questionnaire required participants to rank their COVID-19-related adversity across seven health dimensions. Ordered probits were used to identify variables contributing to adversity. Linear and logit regressions were applied to determine the impact of adversity on HRQoL, defined using AQoL-8D HSUs. Qualitative data were examined thematically. RESULTS: N = 1666 PwMS (average age 58.5; 79.8% female; consistent with the clinical presentation of MS) entered the study, with n = 367 (22.0%) exposed to the 112-day lockdown. Lockdown exposure and disability severity were strongly associated with higher adversity rankings (p < 0.01). Higher adversity rankings were associated with lower HSUs. Participants reporting major adversity, across measured health dimensions, had a mean HSU 0.161 (p < 0.01) lower than participants reporting no adversity and were more likely (OR: 2.716, p < 0.01) to report a clinically significant HSU reduction. Themes in qualitative data supported quantitative findings. CONCLUSIONS: We found that COVID-19-related adversity reduced the HRQoL of PwMS. Our HSU estimates can be used in health economic models to evaluate lockdown cost-effectiveness for people with complex and chronic (mainly neurological) diseases.

Self-reported behaviour change among multiple sclerosis community members and interested laypeople 6 months following participation in a free online course about multiple sclerosis.

ISSUE ADDRESSED: Evaluated the impact of the Understanding Multiple Sclerosis (MS) massive open online course, which was intended to increase understanding and awareness about MS, on self-reported health behaviour change 6 months after course completion. METHODS: Observational cohort study evaluating precourse(baseline) and postcourse (immediately postcourse and six-month follow-up) survey data. The main study outcomes were self-reported health behaviour change; change type; and measurable improvement. We also collected participant characteristic data (eg, age, physical activity). We compared participants who reported health behaviour change at follow-up to those who did not and compared those who improved to those who did not using χ2 and t tests. Participant characteristics, change types and change improvement were described descriptively. Consistency between changes reported immediately postcourse and at the 6-month follow-up was assessed using χ2 tests and textual analysis. RESULTS: N = 303 course completers were included in this study. The study cohort included MS community members (eg, people with MS, healthcare providers) and nonmembers. N = 127 (41.9%) reported behaviour change in ≥1 area at follow-up. Of these, 90 (70.9%) reported a measured change, and of these, 57 (63.3%) showed improvement. The most reported change types were knowledge, exercise/physical activity and diet. N = 81 (63.8% of those reporting a change) reported a change in both immediately and 6 months after course completion, with 72.0% of those that described both changes giving similar responses each time. CONCLUSION: Understanding MS encourages health behaviour change among course completers up to 6 months after course completion. SO WHAT?: An online education intervention can effectively encourage health behaviour change over a 6-month follow-up period, suggesting a transition from acute change to maintenance. The primary mechanisms underpinning this effect are information provision, including both scientific evidence and lived experience, and goal-setting activities and discussions.

Genetically determined serum serine level has a novel causal effect on multiple sclerosis risk and predicts disability progression.

BACKGROUND: There are currently no specific biomarkers for multiple sclerosis (MS). Identifying robust biomarkers for MS is crucial to improve disease diagnosis and management. METHODS: This study first used six Mendelian randomisation methods to assess causal relationship of 174 metabolites with MS, incorporating data from European-ancestry metabolomics (n=8569-86 507) and MS (n=14 802 MS cases, 26 703 controls) genomewide association studies. Genetic scores for identified causal metabolite(s) were then computed to predict MS disability progression in an independent longitudinal cohort (AusLong study) of 203 MS cases with up to 15-year follow-up. RESULTS: We found a novel genetic causal effect of serine on MS onset (OR=1.67, 95% CI 1.51 to 1.84, p=1.73×10-20), such that individuals whose serine level is 1 SD above the population mean will have 1.67 times the risk of developing MS. This is robust across all sensitivity methods (OR ranges from 1.49 to 1.67). In an independent longitudinal MS cohort, we then constructed time-dynamic and time-fixed genetic scores based on serine genetic instrument single-nucleotide polymorphisms, where higher scores for raised serum serine level were associated with increased risk of disability worsening, especially in the time-dynamic model (RR=1.25, 95% CI 1.10 to 1.42, p=7.52×10-4). CONCLUSIONS: These findings support investigating serine as an important candidate biomarker for MS onset and disability progression.

Using qualitative free-text data to investigate the lived experience of the COVID-19 pandemic for a large cohort of Australians with different multiple sclerosis related disability levels.

BACKGROUND: No large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work. METHODS: This was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes. RESULTS: N=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word 'working' was important for PwMS with no disability, and 'support' and 'isolation' for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation. CONCLUSIONS: We found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance.

A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study.

BACKGROUND: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. OBJECTIVE: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. METHODS: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. RESULTS: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = -1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (ß = 0.38, 95% CI = 0.04, 0.72, p = 0.03). CONCLUSION: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.

Estimating the disutility of relapse in relapsing-remitting and secondary progressive multiple sclerosis using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-psychosocial, and SF-6D: implications for health economic evaluation models.

BACKGROUND AND AIMS: Relapses are an important clinical feature of multiple sclerosis (MS) that result in temporary negative changes in quality of life (QoL), measured by health state utilities (HSUs) (disutilities). We aimed to quantify disutilities of relapse in relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and relapse onset MS [ROMS (including both RRMS and SPMS)] and examine these values by disability severity using four multi-attribute utility instruments (MAUIs). METHODS: We estimated (crude and adjusted and stratified by disability severity) disutilities (representing the mean difference in HSUs of 'relapse' and 'no relapse' groups as well as 'unsure' and 'no relapse' groups) in RRMS (n = 1056), SPMS (n = 239), and ROMS (n = 1295) cohorts from the Australian MS Longitudinal Study's 2020 QoL survey, using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-Psychosocial, and SF-6D MAUIs. RESULTS: Adjusted mean overall disutilities of relapse in RMSS/SPMS/ROMS were - 0.101/- 0.149/- 0.129 (EQ-5D-5L), - 0.092/- 0.167/- 0.113 (AQoL-8D), - 0.080/- 0.139/- 0.097 (EQ-5D-5L-Psychosocial), and - 0.116/- 0.161/- 0.130 (SF-6D), approximately 1.5 times higher in SPMS than in RRMS, in all MAUI. All estimates were statistically significant and/or clinically meaningful. Adjusted disutilities of RRMS and ROMS demonstrated a U-shaped relationship between relapse disutilities and disability severity. Relapse disutilities were higher in 'severe' disability than 'mild' and 'moderate' in the SPMS cohort. CONCLUSION: MS-related relapses are associated with substantial utility decrements. As the type and severity of MS influence disutility of relapse, the use of disability severity and MS-type-specific disutility inputs is recommended in future health economic evaluations of MS. Our study supports relapse management and prevention as major mechanisms to improve QoL in people with MS.

Validation of the EQ-5D-5L and psychosocial bolt-ons in a large cohort of people living with multiple sclerosis in Australia.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the central nervous system which results in disability over time and reduced quality of life. To increase the sensitivity of the EQ-5D-5L for psychosocial health, four bolt-on items from the AQoL-8D were used to create the nine-item EQ-5D-5L-Psychosocial. We aimed to externally validate the EQ-5D-5L-Psychosocial in a large cohort of people with MS (pwMS) and explore the discriminatory power of the new instrument with EQ-5D-5L/AQoL-8D. METHODS: A large representative sample from the Australian MS Longitudinal Study completed the AQoL-8D and EQ-5D-5L (including EQ VAS) and both instruments health state utilities (HSUs) were scored using Australian tariffs. Sociodemographic/clinical data were also collected. External validity of EQ-5D-5L-Psychosocial scoring algorithm was assessed with mean absolute errors (MAE) and Spearman's correlation coefficient. Discriminatory sensitivity was assessed with an examination of ceiling/floor effects, and disability severity classifications. RESULTS: Among 1683 participants (mean age: 58.6 years; 80% female), over half (55%) had moderate or severe disability. MAE (0.063) and the distribution of the prediction error were similar to the original development study. Mean (± standard deviation) HSUs were EQ-5D-5L: 0.58 ± 0.32, EQ-5D-5L-Psychosocial 0.62 ± 0.29, and AQoL-8D: 0.63 ± 0.20. N = 157 (10%) scored perfect health (i.e. HSU = 1.0) on the EQ-5D-5L, but reported a mean HSU of 0.90 on the alternative instruments. The Sleep bolt-on dimension was particularly important for pwMS. CONCLUSIONS: The EQ-5D-5L-Psychosocial is more sensitive than the EQ-5D-5L in pwMS whose HSUs approach those reflecting full health. When respondent burden is taken into account, the EQ-5D-5L-Psychosocial is preferential to the AQoL-8D. We suggest a larger confirmatory study comparing all prevalent multi-attribute utility instruments for pwMS.

Superior effects of natalizumab versus other DMTs on patient-reported outcomes in people with multiple sclerosis.

BACKGROUND: Little is known about the comparative effectiveness of multiple sclerosis (MS) disease-modifying therapies (DMTs) on patient-reported outcomes in MS. We compared the effects of natalizumab to other DMTs in relation to MS symptom severity, quality of life, disability, disease progression and employment outcomes using real-world data. METHODS: We included 2817 observations in 2015, 2016 and 2017 from 1382 participants in the Australian MS Longitudinal Study. Information on treatment, health and employment outcomes was prospectively collected by questionnaires. Marginal structural models with interaction terms for DMT×time were used to compare natalizumab and other comparator treatment groups. RESULTS: Natalizumab was associated with improvements over time, or general trends of improvement, in the severity of many symptoms and work productivity loss. Compared with any other DMTs, natalizumab was associated with superior effects over time for 8 of 23 patient-reported outcomes, with similar directions of effect observed for another 6, demonstrating consistency. There were no differences in effect for spasticity, fatigue, pain, feelings of depression, disability, European quality of life five dimension index, presenteeism and work status. Natalizumab did not perform significantly worse over time compared with any other DMTs for any of the outcomes. CONCLUSIONS: Natalizumab was associated with superior outcomes over time for many patient-reported health and employment outcomes when compared with other DMTs in this large prospective cohort study. These findings may influence treatment selection in clinical practice and future treatment cost-effectiveness analyses.

Increasing incidence and prevalence of multiple sclerosis in the Greater Hobart cohort of Tasmania, Australia.

BACKGROUND: The Greater Hobart region (42.5°S) of Tasmania has consistently had the highest recorded prevalence and incidence rates of multiple sclerosis (MS) in Australia. We reassessed MS epidemiology in 2009-2019 and assessed longitudinal changes over 68 years. METHODS: Cases recruited from clinic-based datasets and multiple other data sources. 2019 prevalence and 2009-2019 annual incidence and mortality rates estimated, and differences assessed using Poisson regression. RESULTS: 436 MS cases resident on prevalence day were identified, and 130 had symptom onset within 2009-2019. Prevalence 197.1/100 000 (95% CI 179.4 to 216.5; 147.2/100 000 age standardised, 95% CI 126.5 to 171.3), a 36% increase since 2001 and 3.1-fold increase since 1961. 2009-2019 incidence rate=5.9/100 000 person-years, 95% CI 5.0 to 7.0 (6.1/1000 000 age standardised, 95% CI 4.7 to 7.9), a 2.8-fold increase since 1951-1961 and 65% since 2001-2009. 2009-2019 mortality rate=1.5/100 000 person-years, 95% CI 1.1 to 2.2 (0.9/100 000 age standardised, 95% CI 0.4 to 1.7), comparable to 2001-2009 (1.0/100 000) but reduced by 61% from 1951 to 1959 (2.1/100 000). 2001-2009 standardised mortality ratio=1.0 in 2009-2019, decreased from 2.0 in 1971-1979. Female:male prevalence sex ratio was 2.8, comparable to the 2009 value (2.6); incidence sex ratio (2.9) increased from 2001 to 9 (2.1). Comparisons with Newcastle, Australia (latitude=32.5°S) demonstrate a near complete abrogation of the latitudinal gradients for prevalence (ratio=1.0) and incidence (ratio=1.1), largely attributable to changing Hobart demography. CONCLUSIONS: Prevalence and incidence of MS continue to increase significantly in Hobart, alongside marked reductions in mortality and increased case longevity. The marked increase in incidence is of particular note and may reflect longstanding changes in MS risk behaviours including changing sun exposure, obesity rates, and smoking behaviours, particularly in females. Falling mortality contributes to increase longevity and prevalence, likely reflecting improved overall MS healthcare and implementation of disease-modifying therapy.

Poor sleep and multiple sclerosis: associations with symptoms of multiple sclerosis and quality of life.

BACKGROUND: Sleep difficulties are common in people with multiple sclerosis (MS), but whether associations between poor sleep quality and quality of life are independent of MS symptoms, obesity and other MS-related factors remains unclear. METHODS: Cross-sectional analyses of data from the Australian MS Longitudinal Study (n=1717). Sleep was assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and International Restless Legs Syndrome Study Group Rating Scale; health-related quality of life using the Assessment of Quality-of-Life 8-D. RESULTS: Poor sleep quality was common (67%), and more common than in community samples. Sleep measures clustered independently within MS symptoms. The clusters 'fatigue and cognitive', 'feelings of anxiety and depression', 'pain and sensory', were independently associated with poor sleep quality. Quality-of-Life utility scores were a clinically meaningful 0.19 units lower in those with poor sleep. Sleep quality, daytime sleepiness and restless leg syndrome were associated with reduced quality of life, independent of MS-related symptoms and body mass index. CONCLUSION: Poor sleep quality is common in MS and was strongly associated with worse health-related quality of life, independent of other MS symptoms and did not cluster with other common MS symptoms. Improving sleep quality may substantially improve quality of life in people with MS.

Estimating the impact of work difficulties, work self-efficacy and work psychological safety on MS-related work productivity loss.

BACKGROUND: A comprehensive understanding of factors associated with multiple sclerosis (MS)-related work productivity loss will inform targeted interventions. We have previously shown the strong impact of symptom severity on MS-related work productivity loss. However, the effect of work difficulties, work self-efficacy and work psychological safety is yet to be well evaluated in this context. OBJECTIVES: This study evaluates the association between work difficulties, work self-efficacy and work psychological safety, and MS-related presenteeism, absenteeism and total work productivity loss. METHODS: We analysed data from employed participants of the Australian MS Longitudinal Study (AMSLS) who took part in both the 2015 Medication and Disease Course survey, and 2015 Employment survey (n = 744). Data were analysed using Cragg Hurdle regression models. RESULTS: We found that low workplace self-esteem, interpersonal difficulties at work and work self-efficacy were associated with total work productivity loss. In a multivariable model, a 10-unit decrease in workplace self-esteem, increase in interpersonal difficulties at work and 5-unit increase in work self-efficacy were independently associated with a 3.75% increase, 2.89% increase and 3.36% reduction in total work productivity loss, respectively. When separating total work productivity loss in presenteeism and absenteeism, stronger effects were seen for presenteeism than absenteeism. Surprisingly, work psychological safety was not associated with MS-related work productivity loss. CONCLUSION: Work psychosocial well-being such as self-confidence at work, work self-efficacy and interpersonal difficulties at work are crucial factors governing work productivity in people with MS (PwMS). Multidisciplinary support team assistance of PwMS in symptom self-care, skills around effective communication about MS in the workplace, the psychological impact of work and the modification of work demands may positively influence the employment outcomes.

Long-term trajectories of employment status, workhours and disability support pension status, after a first episode of CNS demyelination.

BACKGROUND: People with multiple sclerosis face significant employment-related challenges, with little known of the drivers of these outcomes. OBJECTIVE: We examined prospective trajectories of employment-related outcomes up to 11 years following a first episode of central nervous system (CNS) demyelination (FCD). METHODS: Participants were aged 18-59 years, at FCD, with at least two observations and were employed at study entry or anytime during follow-up (n = 207). Outcomes were employment status (full-time, part-time and unemployed), average workhours per week and disability support pension (DSP; receiving/not receiving). We used group-based trajectory modelling to identify groups with common trajectories. Factors associated with trajectory membership were explored using log-multinomial regression. RESULTS: Distinct trajectories were identified for employment (4), workhours (4) and DSP (2). Compared with stable full-time, female sex was strongly associated with being in the stable part-time trajectory (risk ratio (RR): 5.35; 95% confidence interval (CI) = 2.56-11.20; p < 0.001). A greater level of disability at 5-year review (RR: 1.35; 95% CI = 1.19-1.53) and having more than two comorbidities at baseline (RR: 2.77; 95% CI = 1.37-5.64) were associated with being in early and late deteriorated employment trajectories, respectively. Compared with the increased part-time trajectory, every additional relapse during the 5 years post-FCD was associated with a 10% increased risk of being in the reduced part-time trajectory (RR = 1.10; 95%CI = 1.00-1.22). For every additional EDSS point at 5-year review, the risk of being in the DSP trajectory increased (RR = 1.21; 95% CI = 1.05-1.41). CONCLUSION: These trajectories indicate substantial heterogeneity and the complex impact of MS on employment from its earliest timepoints. Understanding these trends could enable better targeting of interventions to facilitate workforce retention, particularly for females, those with a higher number of comorbidities, more frequent relapses and greater rate of disability accrual.

The effect of national disease-modifying therapy subsidy policy on long-term disability outcomes in people with multiple sclerosis.

BACKGROUND: Disease-modifying therapies (DMTs) are used to treat people with relapsing-onset multiple sclerosis (ROMS), but our knowledge is largely limited to their short-term effects. OBJECTIVE: To determine (1) the impact of national-level DMT subsidy policy on DMT use and health outcomes in people with MS (PwMS) and (2) the long-term effects of DMT on disability and quality of life (QoL; 5-level EQ-5D version (EQ-5D-5L) utility value). METHODS: This observational cohort study compared Australian and New Zealand populations with different levels of DMT availability 10-20 years post-ROMS diagnosis. Between-country differences were assessed using standardised differences. Associations were assessed with multivariable linear regression models. RESULTS: We recruited 328 Australians and 256 New Zealanders. The Australian cohort had longer DMT treatment duration, greater proportion of disease course treated and shorter duration between diagnosis and starting DMT. The Australian cohort had lower median Expanded Disability Status Scale (EDSS) (3.5 vs 4.0) and Multiple Sclerosis Severity Score (MSSS) (3.05 vs 3.71) and higher QoL (0.71 vs 0.65). In multivariable models, between-country differences in disability and QoL were largely attributed to differential use of DMT. CONCLUSIONS: This study provides evidence for the impact of national-level DMT policy on disability outcomes in PwMS. Where DMTs are more accessible, PwMS experienced less disability progression and improved QoL 10-20 years post-diagnosis.

Development and psychometric properties of the Multiple Sclerosis Knowledge Assessment Scale: Rasch analysis of a novel tool for evaluating MS knowledge.

BACKGROUND: Multiple sclerosis (MS)-related knowledge is an important evaluation metric for health education interventions. However, few MS knowledge assessment tools are currently available for use. OBJECTIVES: This study aims to develop a reliable and valid Multiple Sclerosis Knowledge Assessment Scale (MSKAS) for use in the MS community and the general public. METHODS: The MSKAS was developed using a Delphi study methodology and was administered to participants in the first open enrolment of the Understanding Multiple Sclerosis (UMS) online course. Rasch analysis was used to examine its psychometric properties and develop the final scale. RESULTS: Experts from across the MS community participated in the development of the MSKAS, resulting in an initial scale of 42 items. Five hundred and forty-three UMS participants completed the MSKAS; 89% were female and 30% were people with MS. The final unidimensional 22-item scale has a person separation index of 2.16, a person reliability index of 0.82, an item separation index of 11.19, and a Cronbach's alpha (kr-20) test reliability of 0.87. CONCLUSION: The MSKAS is a unidimensional scale with good construct validity and internal consistency. The MSKAS has the potential to be useful for the assessment of MS knowledge in research and clinical practice.

Feelings of depression, pain and walking difficulties have the largest impact on the quality of life of people with multiple sclerosis, irrespective of clinical phenotype.

BACKGROUND: The symptoms that have the largest impact on health-related quality of life (HRQoL) in people with multiple sclerosis (MS) may vary by MS phenotype (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)). Knowing these symptoms assists in symptom management. OBJECTIVE: To examine the associations between 13 common MS symptoms and HRQoL in the total sample and stratified by MS phenotype. METHOD: The study included 1985 participants. HRQoL was measured with two multi-attribute utility instruments: assessment of quality of life with eight dimensions (AQoL-8D) and European quality of life with five dimensions and five levels for each dimension (EQ-5D-5L). Multivariable linear regression was used to identify the symptoms that had the largest impact on the HRQoLs. RESULTS: Feelings of depression, pain, fatigue, and feelings of anxiety were most strongly associated with AQoL-8D and EQ-5D-5L. Walking difficulties additionally contributed to reduced EQ-5D-5L. The strongest single predictors in the multivariable analyses were feelings of depression or pain for AQoL-8D and walking difficulties for EQ-5D-5L, irrespective of MS phenotype. CONCLUSION: The strongest single predictors for the AQoL-8D and EQ-5D-5L were feelings of depression, pain and walking difficulties, irrespective of MS phenotype. Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS.

Risk factors for leaving employment due to multiple sclerosis and changes in risk over the past decades: Using competing risk survival analysis.

BACKGROUND: No studies have assessed changes in employment survival in multiple sclerosis (MS) populations over recent decades, including the introduction of disease-modifying therapies (DMTs). OBJECTIVES: To evaluate factors associated with leaving employment due to MS; to assess whether the risk of leaving employment has changed over recent decades in Australia, stratified by MS phenotype. METHODS: We included 1240 participants who were working before MS diagnosis. Information on employment status, reasons for leaving employment and year of leaving were collected. Data were analysed using competing risk survival analysis. RESULTS: Males, progressive MS, lower education level and older age at diagnosis were associated with a higher sub-distribution hazard of leaving employment. Compared to the period before 2010, the sub-distribution hazard during 2010-2016 for relapsing-remitting multiple sclerosis (RRMS) was reduced by 43% (sub-distribution hazard ratio (sHR) 0.67, 95% confidence interval (CI): 0.50 to 0.90), while no significant reduction was seen for primary-progressive multiple sclerosis (PPMS) (sHR 1.25, 95% CI: 0.72 to 2.16) or secondary-progressive multiple sclerosis (SPMS) (sHR 1.37, 95% CI: 0.84 to 2.25). CONCLUSION: Males, people with progressive MS and those of lower education level were at higher risk of leaving employment. The differential changed risk of leaving employment between people with different MS phenotype after 2010 coincides with the increased usage of high-efficacy DMTs for RRMS.