Disease-modifying therapies and cost-of-illness progression among people newly diagnosed with multiple sclerosis: a national register-based cohort study covering treatment initiation with interferons, glatiramer acetate or natalizumab.

OBJECTIVES: Disease-modifying therapies (DMTs) can slow disease progression in multiple sclerosis (MS). The objective of this study was to explore the cost-of-illness (COI) progression among newly diagnosed people with MS in relation to the first DMT received. DESIGN AND SETTING: A cohort study using data from nationwide registers in Sweden. PARTICIPANTS: People with MS (PwMS) in Sweden first diagnosed in 2006-2015, when aged 20-55, receiving first-line therapy with interferons (IFN), glatiramer acetate (GA) or natalizumab (NAT). They were followed up through 2016. OUTCOME MEASURES: Outcomes (in Euros, €) were: (1) secondary healthcare costs: specialised outpatient and inpatient care including out-of-pocket expenditure, DMTs including hospital-administered MS therapies, and prescribed drugs, and (2) productivity losses: sickness absence and disability pension. Descriptive statistics and Poisson regression were computed, adjusting for disability progression using the Expanded Disability Status Scale. RESULTS: 3673 newly diagnosed PwMS who were treated with IFN (N=2696), GA (N=441) or NAT (N=536) were identified. Healthcare costs were similar for the INF and GA groups, while the NAT group had higher costs (p value<0.05), owing to DMT and outpatient costs. IFN had lower productivity losses than NAT and GA (p value>0.05), driven by fewer sickness absence days. NAT had a trend towards lower disability pension costs compared with GA (p value>0.05). CONCLUSIONS: Similar trends over time for healthcare costs and productivity losses were identified across the DMT subgroups. PwMS on NAT maintained their work capacity for a longer time compared with those on GA, potentially leading to lower disability pension costs over time. COI serves as an objective measure to explore the importance of DMTs in maintaining low levels of progression of MS over time.

Excess costs of multiple sclerosis: a register-based study in Sweden.

BACKGROUND AND OBJECTIVE: Population-based estimates of the socioeconomic burden of multiple sclerosis (MS) are limited, especially regarding primary healthcare. This study aimed to estimate the excess costs of people with MS that could be attributed to their MS, including primary healthcare. METHODS: An observational study was conducted of the 2806 working-aged people with MS in Stockholm, Sweden and 28,060 propensity score matched references without MS. Register-based resource use was quantified for 2018. Annual healthcare costs (primary, specialised outpatient, and inpatient healthcare visits along with prescribed drugs) and productivity losses (operationalised by sickness absence and disability pension days) were quantified using bottom-up costing. The costs of people with MS were compared with those of the references using independent t-tests with bootstrapped 95% confidence intervals (CIs) to isolate the excess costs of MS from the mean difference. RESULTS: The mean annual excess costs of MS for healthcare were €7381 (95% CI 6991-7816) per person with MS with disease-modifying therapies as the largest component (€4262, 95% CI 4026-4497). There was a mean annual excess cost for primary healthcare of €695 (95% CI 585-832) per person with MS, comprising 9.4% of the excess healthcare costs of MS. The mean annual excess costs of MS for productivity losses were €13,173 (95% CI 12,325-14,019) per person with MS, predominately from disability pension (79.3%). CONCLUSIONS: The socioeconomic burden of MS in Sweden from healthcare consumption and productivity losses was quantified, updating knowledge on the cost structure of the substantial excess costs of MS.

Early vs. late treatment initiation in multiple sclerosis and its impact on cost of illness: A register-based prospective cohort study in Sweden.

Background: Early treatment with disease modifying therapies (DMTs) for multiple sclerosis (MS) has been associated with lower disability progression; the aim was to explore its association with cost of illness (COI) in MS. Methods: All people with relapsing-remitting MS in the Swedish MS register, aged 20-57 years and receiving their first MS DMT in 2006-2009, were followed in nationwide registers for 8 years. Healthcare costs (in- and outpatient healthcare, DMTs and other prescribed drugs), and productivity losses (sickness absence and disability pension) of individuals receiving therapy in ≤6 months after diagnosis (early treatment group) were compared to those receiving therapy >6 months (late treatment group). Using Poisson regressions, the mean COI per patient per year, and per group, was estimated, adjusted for disability progression. Results: The early treatment group comprised 74% of the 1562 individuals included in the study. The early treatment group had lower productivity losses over time. Both groups had similar healthcare costs, which first increased and then decreased over time. Conclusions: Early DMT in MS could result in lower productivity losses possibly through maintained work capacity. COI serves as an objective measure showing the advantage of early vs. late treatment initiation in MS.

Cost-of-Illness Progression Before and After Diagnosis of Multiple Sclerosis: A Nationwide Register-Based Cohort Study in Sweden of People Newly Diagnosed with Multiple Sclerosis and a Population-Based Matched Reference Group.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease associated with increased healthcare utilisation and productivity losses. OBJECTIVE: The objective of this study was to explore the progression of healthcare costs and productivity losses before and after diagnosis of MS in comparison to that of a population-based matched reference group. METHODS: We conducted a nationwide, Swedish register-based cohort study of working-aged people with MS diagnosed in 2010-12 (n = 1988) and population-based matched references without MS (n = 7981). Nine years of observation spanned from 4 years prior (Y-4) to 4 years (Y+4) after the year of diagnosis (Y0). Differences in annual all-cause healthcare costs (inpatient and specialised outpatient healthcare as well as pharmacy-dispensed prescribed drugs) and costs of productivity loss (days with sickness absence and disability pension) were estimated between the people with MS and references using t tests with 95% confidence intervals. The average excess costs of MS were estimated using generalised estimating equation models. RESULTS: People with multiple sclerosis had higher costs before the diagnosis of MS and also thereafter. The mean differences in healthcare costs and productivity losses between the people with MS and matched references in Y-4 were 216 EUR (95% confidence interval 58-374) and 1540 EUR (95% confidence interval 848-2233), with larger cost excesses observed in later study years. Summarising the 9 study years, people with MS had fivefold higher excess healthcare costs than references, and more than twice as high productivity losses. CONCLUSIONS: Excess healthcare costs and productivity losses occur already before the diagnosis of MS and increase with time. The excess costs findings before diagnosis could suggest that an earlier diagnosis might lead to reduced excess costs of MS over time.

Multiple sclerosis (MS) is a neurological disease that can affect many parts of everyday life, including work. We studied the extra costs related to MS. Extra costs were defined as the difference in costs between people with MS and the general population in Sweden. To do this, we compared the costs of working-aged individuals with MS from 4 years before to 4 years after the year of MS diagnosis with those of individuals without MS. For each year, we measured the healthcare consumption and days absent owing to sickness absence or a disability pension. We found that people with MS had larger costs already before the diagnosis of MS. For all types of costs we studied, there were extra costs. The extra costs became larger with time and had a steep increase around the year of MS diagnosis. When we summarised the costs from all 9 years, people with MS had five times higher annual costs related to healthcare consumption than those without MS. There were also twice as high costs for lost production from days absent with sickness absence or a disability pension. While our data from national registers had objective measurements of the included costs, it did not include information on the costs for drugs administered in healthcare, rehabilitation or informal care from family members. We studied the costs of all people diagnosed with MS in 2010­12 in Sweden, related their disease trajectory with their costs, as well as compared their costs with the costs of a group from the general population. Our results of the extra costs of MS prior to diagnosis could suggest an unmet need. Earlier diagnosis and quickly starting treatment may lead to lower extra costs of MS over time.

Cost-of-illness trajectories among people with multiple sclerosis by comorbidity: A register-based prospective study in Sweden.

BACKGROUND: Comorbidities are common among people with multiple sclerosis (PwMS); yet, their impact on the cost-of-illness (COI) in MS is unknown. OBJECTIVE: Explore the heterogeneity in COI trajectories among newly diagnosed PwMS in relation to type of comorbidity. METHODS: A nationwide longitudinal cohort study, using prospectively collected Swedish register data for seven years. The COI/year of 639 PwMS diagnosed in 2006, when aged 25-60, was estimated until 2013. Using healthcare data, PwMS were categorised into six comorbidity groups: ocular; cardiovascular, genitourinary or cancer disease; musculoskeletal; mental; neurological other than MS; and injuries. One group of PwMS without comorbidity was also created. Group-based trajectory modelling was applied, examining different COI trajectories within each comorbidity group. RESULTS: Across the seven follow-up years, PwMS with mental comorbidities had the highest COI overall (€36,482). Four COI trajectories were identified within each comorbidity group; the largest trajectory had high healthcare costs and productivity losses (36.3%-59.6% of PwMS, across all comorbidity groups). 59.6% of PwMS with mental comorbidity had high healthcare costs and productivity losses. CONCLUSION: High COI and heterogeneity in COI trajectories could be partly explained by the presence of chronic comorbidities in the year around MS diagnosis, including the presence of mental comorbidity.

Diagnosis-specific sickness absence and disability pension before and after multiple sclerosis diagnosis: An 8-year nationwide longitudinal cohort study with matched references.

BACKGROUND: Multiple sclerosis (MS) typically onsets when of working age and may reduce work capacity. Previous studies have examined the risk of sickness absence (SA) and disability pension (DP) among MS patients, however, limited knowledge is available on whether MS patients have an excess risk for SA/DP when compared with the general population in Sweden. Moreover, no information exists on the actual diagnoses for SA and DP among MS patients and whether the patterns of SA/DP diagnoses differs to those without MS. We aimed to explore diagnosis-specific SA and DP among working-aged MS patients both before and after MS diagnosis, in comparison to the levels and distributions of SA and DP diagnoses of a matched reference group and analyze the risk of diagnosis-specific DP. MATERIALS AND METHODS: Longitudinal Swedish register data of the 2567 MS patients diagnosed with MS in 2009-2012 when aged 25-59 and 10,268 population-based matched references (matched on sex, age, educational level, type of living area, and country of birth) were analysed regarding annual diagnosis-specific SA and DP in the four years before and four years after MS diagnosis. Annual differences in the mean numbers of SA and/or DP net days were calculated with 95% confidence intervals (CI). Hazard ratios (HR) with 95% CI from Cox proportional hazard models were used to compare risks for new all-cause and diagnosis-specific DP after MS diagnosis among the MS patients and references. RESULTS: The mean SA/DP net days/year increased among MS patients over follow-up, due to both MS and other diagnoses. During follow-up, around 50% of MS patients had some SA/DP compared to 20% of references. The mean days of SA/DP among the MS patients compared to references increased from 10.3 more days (95% CI: 6.6-14.2) four years prior to MS diagnosis to 68.9 days (62.8-75.1) 4 years after MS diagnosis. Although most new DP among MS patients were due to MS, 15% were not. The adjusted HR for all-cause DP was 23.1 (18.1-29.5). MS patients also had higher risks of new DP due to all diagnoses except MS (HR 3.4; 2.4-4.8), musculoskeletal (HR 2.6; 1.1-6.0) and mental (HR 2.0; 1.1-3.6) diagnoses compared with references. CONCLUSION: MS patients had higher levels of SA/DP days/year than the references, already 4 years before the MS diagnosis, and increasingly so thereafter. The excess of SA/DP prior to MS diagnosis could be related to MS onset. However, the excess of SA/DP days were not all due to MS diagnoses, even after being diagnosed with MS. MS patients had a higher risk of having a new DP after being diagnosed with MS in total, but also for diagnoses other than MS.

Healthcare, Sickness Absence, and Disability Pension Cost Trajectories in the First 5 Years After Diagnosis with Multiple Sclerosis: A Prospective Register-Based Cohort Study in Sweden.

OBJECTIVES: The aim was to longitudinally explore the healthcare, sickness absence (SA), and disability pension (DP) cost trajectories among newly diagnosed people with multiple sclerosis (MS), and investigate whether trajectories differ by year of MS diagnosis, sociodemographics, and multi-morbidity. METHODS: People with MS in Sweden, aged 25-60 years and with a new MS diagnosis in the years 2006, 2007, 2008, or 2009 (four different cohorts) were identified in nationwide registers and followed prospectively for 5 years, determining the annual, per patient, direct (inpatient and specialised outpatient healthcare, co-payments, and dispensed drugs) and indirect (SA and DP) costs. Descriptive statistics and group-based trajectories were computed. RESULTS: In total, 3272 people with new MS were identified. In all cohorts, direct costs increased the year after diagnosis and thereafter declined (e.g. from €8261 to €9128, and to €7953, 5 years after diagnosis, for the 2006 cohort). SA costs continuously decreased over 5 years, while DP costs increased (e.g. from €9795 to €2778 vs. from €7277 to €15,989, respectively, for the 2006 cohort). When pooling all cohorts, four trajectories of direct and indirect costs were identified. A total of 32.1% of people with MS had high direct and indirect costs, which first increased and then decreased; the contrary was seen for trajectories with low direct and indirect costs. CONCLUSIONS: There is heterogeneity in the development of MS costs over time after diagnosis; decreasing cost trajectories could be associated with the use of innovative MS therapies, slowing disease progression over time.

Costs of illness progression for different multiple sclerosis phenotypes: a population-based study in Sweden.

BACKGROUND: Little is known of how the cost of illness and health-related quality of life changes over time after a diagnosis of multiple sclerosis. OBJECTIVES: The aim was thus to explore the progression of annual direct and indirect costs and health-related quality of life among people with multiple sclerosis of working ages, following diagnosis with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) or conversion to secondary progressive multiple sclerosis (SPMS) after RRMS. METHODS: Swedish nationwide registers were linked to estimate the annual cost of illness in 2006-2013 among people with a registered new multiple sclerosis phenotype, including: direct costs, indirect costs, and health-related quality of life. RESULTS: Drugs and indirect costs for sick leave were the main cost drivers after diagnosis with RRMS. After conversion to SPMS, the RRMS cost drivers were replaced by indirect costs for disability pension. The main cost driver in newly diagnosed PPMS was indirect costs for sick leave, later replaced by disability pension. Health-related quality of life scores were similar after RRMS and SPMS. CONCLUSIONS: After initial high indirect costs for sick leave, people with RRMS had higher drug costs compared to people with PPMS. Cost drivers during SPMS initially followed the pattern in the RRMS population, but were replaced by indirect costs for disability pension.

Earnings among people with multiple sclerosis compared to references, in total and by educational level and type of occupation: a population-based cohort study at different points in time.

OBJECTIVES: To investigate earnings among people with multiple sclerosis (PwMS) before and after MS diagnosis compared with people without MS, and if identified differences were associated with educational levels and types of occupations. Furthermore, to assess the proportions on sickness absence (SA) and disability pension (DP) in both groups. DESIGN: Population-based longitudinal cohort study, 10 years before until 5 years after MS diagnosis. SETTING: Working-age population using microdata linked from nationwide Swedish registers. PARTICIPANTS: Residents in Sweden in 2004 aged 30-54 years with MS diagnosed in 2003-2006 (n=2553), and references without MS (n=7584) randomly selected by stratified matching. OUTCOME MEASURES: Quartiles of earnings were calculated for each study year prior to and following the MS diagnosis. Mean earnings, by educational level and type of occupation, before and after diagnosis were compared using t-tests. Tobit regressions investigated the associations of earnings with individual characteristics. The proportions on SA and/or DP, by educational level and type of occupation, for the diagnosis year and 5 years later were compared. RESULTS: Differences in earnings between PwMS and references were observed beginning 1 year before diagnosis, and increased thereafter. PwMS had lower mean earnings for the diagnosis year (difference=SEK 28 000, p<0.05), and 5 years after diagnosis, this difference had more than doubled (p<0.05). These differences remained after including educational level and type of occupation. Overall, the earnings of PwMS with university education and/or more qualified occupations were most like their reference peers. The proportions on SA and DP were higher among PwMS than the references. CONCLUSIONS: The results suggest that the PwMS' earnings are lower than the references' beginning shortly before MS diagnosis, with this gap increasing thereafter. Besides SA and DP, the results indicate that educational level and type of occupation are influential determinants of the large heterogeneity of PwMS' earnings.

Trajectories of disposable income among people of working ages diagnosed with multiple sclerosis: a nationwide register-based cohort study in Sweden 7 years before to 4 years after diagnosis with a population-based reference group.

OBJECTIVES: To describe how disposable income (DI) and three main components changed, and analyse whether DI development differed from working-aged people with multiple sclerosis (MS) to a reference group from 7 years before to 4 years after diagnosis in Sweden. DESIGN: Population-based cohort study, 12-year follow-up (7 years before to 4 years after diagnosis). SETTING: Swedish working-age population with microdata linked from two nationwide registers. PARTICIPANTS: Residents diagnosed with MS in 2009 aged 25-59 years (n=785), and references without MS (n=7847) randomly selected with stratified matching (sex, age, education and country of birth). PRIMARY AND SECONDARY OUTCOME MEASURES: DI was defined as the annual after tax sum of incomes (earnings and benefits) to measure individual economic welfare. Three main components of DI were analysed as annual sums: earnings, sickness absence benefits and disability pension benefits. RESULTS: We found no differences in mean annual DI between people with and without MS by independent t-tests (p values between 0.15 and 0.96). Differences were found for all studied components of DI from diagnosis year by independent t-tests, for example, in the final study year (2013): earnings (-64 867 Swedish Krona (SEK); 95% CI-79 203 to -50 528); sickness absence benefits (13 330 SEK; 95% CI 10 042 to 16 500); and disability pension benefits (21 360 SEK; 95% CI 17 380 to 25 350). A generalised estimating equation evaluated DI trajectory development between people with and without MS to find both trajectories developed in parallel, both before (-4039 SEK; 95% CI -10 536 to 2458) and after (-781 SEK; 95% CI -6988 to 5360) diagnosis. CONCLUSIONS: The key finding of parallel DI trajectory development between working-aged MS and references suggests minimal economic impact within the first 4 years of diagnosis. The Swedish welfare system was responsive to the observed reductions in earnings around MS diagnosis through balancing DI with morbidity-related benefits. Future decreases in economic welfare may be experienced as the disease progresses, although thorough investigation with future studies of modern cohorts are required.