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.

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.

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.

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.

Using the EQ-5D-5L to investigate quality-of-life impacts of disease-modifying therapy policies for people with multiple sclerosis (MS) in New Zealand.

BACKGROUND: Health state utilities (HSU) are a health-related quality-of-life (HRQoL) input for cost-utility analyses used for resource allocation decisions, including medication reimbursement. New Zealand (NZ) guidelines recommend the EQ-5D instruments; however, the EQ-5D-5L may not sufficiently capture psychosocial health. We evaluated HRQoL among people with multiple sclerosis (MS) in NZ using the EQ-5D-5L and assessed the instrument's discriminatory sensitivity for a NZ MS cohort. METHODS: Participants were recruited from the NZ MS Prevalence Study. Participants self-completed a 45-min online survey that included the EQ-5D-5L/EQ-VAS. Disability severity was classified using the Expanded Disability Status Scale (EDSS) to categorise participant disability as mild (EDSS: 0-3.5), moderate (EDSS: 4.0-6.0) and severe (EDSS: 6.5-9.5). Anxiety/depression were also measured using the Hospital Anxiety and Depression Score (HADS). In the absence of an EQ-5D-5L NZ tariff, HSUs were derived using an Australian tariff. We evaluated associations between HSUs and participant characteristics with linear regression models. RESULTS: 254 participants entered the study. Mean age was 55.2 years, 79.5% were female. Mean (SD) EQ-5D-5L HSU was 0.58 (0.33). Mean (SD) HSUs for disability categories were: mild 0.80 ± 0.17, moderate 0.57 ± 0.21 and severe 0.14 ± 0.32. Twelve percent reported HSU = 1.0 (i.e., no problems in any domain). Participants who had never used a disease-modifying therapy reported a lower mean HSU. Multivariable modelling found that the HADS anxiety score was not associated with EQ-5D-5L. CONCLUSIONS: HRQoL for people with MS in NZ was lower than comparable countries, including Australia. We suggest a comparison with other generic tools that may have improved sensitivity to mental health.

Does health-related quality of life differ between people with relapse onset and progressive onset Multiple Sclerosis?

BACKGROUND: Multiple Sclerosis (MS) can be categorised as relapse onset MS (ROMS) and progressive onset MS (PROMS). We aimed to examine if health-related quality of life (in terms of health state utilities [HSUs] and dimensional scores) differed by onset type, in which health dimensions the differences were most pronounced, and whether these differences remained when stratified by disability severity. METHODS: We estimated HSUs and the unique composite 'super-dimension' and 'individual dimension' scores (crude, age, sex, disease duration and disease modifying therapies use adjusted; and stratified by onset type and disability severity) for a sample of 1577 participants in the Australian MS Longitudinal Study, using the Assessment of Quality of Life (AQoL)-8D. RESULTS: Adjusted mean overall HSU of PROMS was 0.55, 0.07 lower than ROMS. Adjusted mean physical and psychosocial super-dimension scores for PROMS were 0.51 and 0.28, 0.07 and 0.06 lower than for ROMS, respectively. For the individual health dimensions, the largest difference was seen in independent living (-0.12), followed by relationships (-0.07), and self-worth (-0.07). Whilst HSUs and dimensional scores were negatively associated with increasing disability severity in both onset types, estimates by disability severity did not differ between the two cohorts. CONCLUSIONS: Our study provides a comprehensive assessment of the effects of MS onset type on the overall and disability-severity specific HRQoL scores using a detailed preferentially sensitive AQoL-8D instrument. While overall HRQoL was substantially lower in PROMS than in ROMS, the mean HRQoL values for each disability level did not differ by onset type, indicating that future health economic models can use the same HSU inputs for both onset types.

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.

Measuring the health-related quality of life in Australians with multiple sclerosis using the assessment of quality of life-8-dimension (AQoL-8D) multi-attribute utility instrument.

BACKGROUND: Health-related quality of life (HRQoL) has not been assessed in Australians with multiple sclerosis (MS) using a preferentially sensitive multi-attribute utility instrument. OBJECTIVES: To assess HRQoL and to quantify the impact of disability on health state utility values (HSUVs), and the physical and psychosocial health of people with MS using the Assessment of Quality of Life-8-Dimension (AQoL-8D) instrument. METHODS: We estimated HSUVs and the unique composite individual and super dimensional (physical and psychosocial) scores of the AQoL-8D for a large, representative sample (n=1,577) of Australians with MS. The estimates were compared to Australian general population norms and broken down by disability severity, classified as no disability (Expanded Disability Status Scale [EDSS] level: 0), mild (EDSS: 1-3.5), moderate (EDSS: 4-6) and severe (EDSS: 6.5-9.5). A multivariable regression model adjusted the association between MS disability severity and HSUVs for age, sex, MS onset type, DMTs usage status, and MS duration. RESULTS: Mean overall HSUV at 0.61 (95% confidence interval [CI]: 0.60-0.62) was 0.18 units lower than the Australian population norm. HSUV decreased with increasing disability severity: 0.81 (95% CI: 0.80-0.83), 0.65 (95% CI: 0.63-0.67), 0.54 (95% CI: 0.52-0.56) and 0.48 (95% CI: 0.46-0.50) for no, mild, moderate and severe disability, respectively. The mean Physical super-dimension score of 0.57 (95% CI: 56-0.58) was 0.21 units lower than the Australian norm and the Psychosocial super-dimension of 0.33(95% CI: 32-0.34) was 0.16 units lower. Lower HRQoL was primarily driven by reduced scores on Independent living (-0.23), Pain (-0.15), Relationships (-0.13), Coping (-0.12), and Self-worth (-0.12). CONCLUSIONS: MS impacts all aspects of HRQoL. Effective pain management and support to maintain independent living, relationships, and self-worth can significantly improve the HRQoL of people with MS. Early diagnosis and affordable access to effective treatments to slow or prevent disability accumulation may also be helpful.

The increasing economic burden of multiple sclerosis by disability severity in Australia in 2017: Results from updated and detailed data on types of costs.

BACKGROUND: Economic costs of Multiple Sclerosis (MS) in Australia were last estimated in 2010 and are likely to have changed over time, especially given this new era of increased access to higher efficacy disease modifying therapies (DMTs) with a strong focus on earlier MS diagnosis and treatment. OBJECTIVES: To provide a comprehensive contemporary analysis of the updated direct and indirect costs of MS in Australia from a societal perspective and to examine how the cost landscape has changed overtime. METHODS: Costs were estimated from the 2016 Economic Impact Survey (EIS) of the Australian MS longitudinal Study (AMSLS) and were stratified by various (indirect and direct) cost categories/sub-categories and disability severity. Disability was assessed with the patient determined disease steps (PDDS) and mapped against the gold-standard Expanded Disability Status Scale (EDSS), and classified as no disability (EDSS level: 0), mild (EDSS 1-3.5), moderate (EDSS 4-6) and severe (EDSS 6.5-9.5). A generalized linear model (GLM) predicted covariate adjusted costs for each disability severity. All costs are presented in 2017 Australian dollars. RESULTS: 488 (15.5% of the 3,163) AMSLS participants completed the survey. Annual costs per person with MS increased 17% from 2010 to $68,382 in 2017, driven largely by increased direct costs (from $16,306 in 2010 to $30,346 in 2017) (particularly those related to DMTs, hospitalizations, consultations, and medical tests), but offset by decreased costs of lost wages (from $29,030 in 2010 to $21,858 in 2017) as a result of recent positive shifts in the employment landscape for Australians with MS. Costs increased with increasing disability severity: $30,561 (95% confidence intervals [CI]: $25,672-$35,451), $55,815 (95%CI: $47,503-$64,126), $76,915 (95%CI: $68,866-$84,964), and $114,813 (95%CI: $102,252-$127,374) for no, mild, moderate and severe disability, respectively. The differences in costs between the four disability groups remained statistically significant even after adjustment for age, sex, DMT usage status, disease course and areas of remoteness. CONCLUSIONS: MS has an increasing economic burden in Australia. The study provides current economic data on MS in Australia that are important for policy development, priority setting and management of public health.

Modelling the impact of multiple sclerosis on life expectancy, quality-adjusted life years and total lifetime costs: Evidence from Australia.

OBJECTIVES: To quantify life expectancy (LE), quality-adjusted life years (QALYs) and total lifetime societal costs for a hypothetical cohort of Australians with multiple sclerosis (MS). METHODS: A 4-state Markov model simulated progression from no/mild to moderate and severe disability and death for a cohort of 35-year-old women over a lifetime horizon. Death risks were calculated from Australian life tables, adjusted by disability severity. State-dependent relapse probabilities and associated disutilities were considered. Probabilities of MS progression and relapse were estimated from AusLong and TasMSL MS epidemiological databases. Annual societal (direct and indirect) costs (2017 Australian dollars) and health-state utilities for each state were derived from the Australian MS Longitudinal Study. Costs were discounted at 5% annually. RESULTS: Mean (95% confidence interval (CI)) LE from age 35 years was 42.7 (41.6-43.8) years. This was 7.5 years less than the general Australian population. Undiscounted QALYs were 28.2 (26.3-30.0), a loss of 13.1 QALYs versus the Australian population. Discounted lifetime costs were $942,754 ($347,856-$2,820,219). CONCLUSION: We have developed a health economics model of the progression of MS, calculating the impact of MS on LE, QALYs and lifetime costs in Australia. It will form the basis for future cost-effectiveness analyses of interventions for MS.