Contact patterns and costs of multiple sclerosis in the Swedish healthcare system-A population-based quantitative study.

BACKGROUND: The burden of disease for persons with multiple sclerosis (MS) and society is changing due to new treatments. Knowledge about the total need for care is necessary in relation to changing needs and new service models. OBJECTIVE: The aim of this study was to describe the contact patterns for MS patients, calculate costs in health care, and create meaningful subgroups to analyze contact patterns. METHODS: All patients diagnosed with MS at Ryhov Hospital were included. All contacts in the region from January 1, 2018, until September 30, 2019, were retrieved from the hospital administrative system. Data about age, sex, contacts, and diagnosis were registered. The cost was calculated using case costing, and costs for prescriptions were calculated from medical files. RESULTS: During the 21-month period, patients (n = 305) had 9628 contacts and 7471 physical visits, with a total cost of $7,766,109. Seventeen percent of the patients accounted for 48% of the visits. The median annual cost was $7386 in the group with 10 or fewer visits, compared to $22,491 in patients with more than 50 visits. CONCLUSION: There are considerable differences in the utilization of care and cost between patients with MS in an unselected population, meaning that the care needs to be better customized to each patient's demands.

The Multiple Sclerosis Treatment Optimization Program.

OBJECTIVE: To design and implement a health system level intervention to reduce escalating multiple sclerosis (MS) disease modifying treatment (DMT) expenditures and improve outcomes. METHODS: We conducted stakeholder meetings, reviewed pharmacy utilization data, and abstracted information in subsets of persons with MS (pwMS) from the electronic health record to identify gaps in, and barriers to improving, quality, and affordability of MS care in Kaiser Permanente Southern California. These results informed the development and implementation of the MS Treatment Optimization Program (MSTOP). RESULTS: The two main gaps identified were under-prescribing of highly effective DMTs (HET, 4.9%) and the preferred formulary DMT (20.9%) among DMT-treated pwMS. The main barriers identified were prescribers' fear of rare but serious HET side effects, lack of MS-specific and health systems science knowledge, Pharma influence, evidence gaps, formulary decisions-based solely on costs, and multidirectional mistrust between neurologists, practice leaders, and health plan pharmacists. To overcome these barriers MSTOP developed four strategies: (1) risk-stratified treatment algorithm to increase use of HETs; (2) an expert-led ethical, cost-sensitive, risk-stratified, preferred formulary; (3) proactive counter-launch campaigns to minimize uptake of new, low-value DMTs; and (4) discontinuation of ineffective DMTs in progressive, non-relapsing MS. The multicomponent MSTOP was implemented through education, training, and expanding access to MS-trained providers, audit and feedback, and continual evidence reviews. INTERPRETATION: The causes of wasteful spending on MS DMTs are complex and require multiple strategies to resolve. We provide herein granular details of how we designed and implemented our health system intervention to facilitate its adaption to other settings and conditions.

Economic burden of highly active relapsing-remitting multiple sclerosis patients in the French national health insurance database.

BACKGROUND: As healthcare management of highly active-relapsing-remitting multiple sclerosis (HA-RRMS) patients is more complex than for the whole multiple sclerosis (MS) population, this study assessed the related economic burden from a National Health Insurance's (NHI's) perspective. RESEARCH DESIGN AND METHODS: Study based on French NHI databases, using individual data on billing and reimbursement of outpatient and hospital healthcare consumption, paid sick leave and disability pension, over 2010-2017. RESULTS: Of the 9,596 HA-RRMS adult patients, data from 7,960 patients were analyzed with at least 2 years of follow-up. Mean annual cost/patient was €29,813. Drugs represented 40% of the cost, hospital care 33%, disability pensions 9%, and all healthcare professionals' visits combined 8%. Among 3,024 patients under 60 years-old with disability pension, disability pension cost €7,168/patient/year. Among 3,807 patients with paid sick leave, sick leave cost €1,956/patient/year. Mean costs were €2,246/patient higher the first year and increased by €1,444 between 2010 and 2015, with a €5,188 increase in drug-related expenditures and a €634 increase in healthcare professionals' visits expenditures but a €4,529 decrease in hospital care expenditures. CONCLUSIONS: The cost of health care sick leaves, and disability pensions of HA-RRMS patients was about twice as high as previously reported cost of MS patients.

New insights into the socio-economic aspects of multiple sclerosis in a cohort of Polish patients.

INTRODUCTION AND OBJECTIVE: The diagnosis of multiple sclerosis (MS) affects the socio-economic aspects of patients' lives and poses new challenges. The objectives of the study were: 1) to determine selected socio-economic aspects of MS in Poland in relation to the disease type and patients' place of residence, and 2) to evaluate the profile of patients via the MS Society (MSS) and the occupational consequences of informing an employer about the diagnosis. MATERIAL AND METHODS: A retrospective, observational study was undertaken to assess a cohort of 375 Polish MS patients. Socio-economic data was collected based on the patients' responses to questions on a questionnaire. Clinical data was obtained from available medical records. RESULTS: Patients with relapsing-remitting MS had a significantly longer time of occupational activity, higher economic status, higher level of education, better relationships with life partner, less likely to benefit from disability benefits, and members of MSS, than patients with progressive types of the disease. The patients living in rural areas had a significantly shorter time of occupational activity, more often experienced a decrease in income, received disability pension, and were less educated than urban residents. Patients who informed their employer about an MS diagnosis significantly more often received support from the company, were professionally active for longer, and less likely to experience a decrease in income. Membership of the MSS were dominated by patients with progressive variants of the disease and advanced disability. CONCLUSIONS: The disease variant and, to a lesser extent, the place of residence, affected the socio-economic aspects of MS. It might be advantageous for the patient to disclose information about MS diagnosis to the employer.

Socioeconomic consequences of multiple sclerosis-A systematic literature review.

Multiple sclerosis (MS) is a challenging and disabling condition, predominantly affecting individuals in their early life, and has an impact functionally, financially, and on quality of life. However, there is a lack of systematic approach towards assessing socioeconomic consequences of MS. Our objective was to systematically review observational analytical studies investigating the socioeconomic consequences of MS. We conducted a systematic review on socioeconomic consequences of MS with a focus on employment-, income-, work ability- and relationship-related outcomes between MS and the general population. Additionally, the educational characteristics were extracted. From 4958 studies identified, 187 were assessed for eligibility and a total of 27 studies from eight countries were included in this qualitative assessment; 32 different outcomes were identified. All studies indicated pronounced differences between MS patients and the general population, for example 15%-30% lower employment, lower earnings and higher social benefits, higher absenteeism and presenteeism proportions, higher work disability (eg, sick-leave days) among MS patients. Some studies also indicated differences in the family or relationship characteristics. There were no apparent differences with regard to educational level. In conclusion, socioeconomic data can serve as robust outcome measures to study various aspects of MS reflecting the broader consequences of the disease.

Impacto económico de las nuevas terapias orales en esclerosis múltiple / Economic impact of the new oral treatments for multiple sclerosis

INTRODUCCIÓN: La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central que se caracteriza por la existencia de inflamación, desmielinización, gliosis y daño axonal. La introducción de dimetilfumarato y teriflunomida ha supuesto un aumento de las alternativas terapéuticas en la primera línea de tratamiento de la EM. El objetivo de este estudio fue evaluar el impacto económico de la incorporación de estas nuevas terapias orales en la Unidad de Referencia (CSUR) del Hospital Universitario Puerta de Hierro Majadahonda. MATERIAL Y MÉTODOS: Se realizó un estudio observacional retrospectivo en la población de pacientes diagnosticados de EM, en tratamiento con fármacos modificadores de la enfermedad durante el año 2015, y su seguimiento se prolongó hasta obtener un seguimiento medio superior a un año de tratamiento. Los datos se recogieron de la historia clínica electrónica y del programa de dispensación de medicamentos a pacientes externos y ambulantes del Servicio de Farmacia. RESULTADOS: Evaluando el coste del cambio del tratamiento en 125 pacientes desde otros fármacos a dimetilfumarato o teriflunomida y comparando con el coste que habría supuesto el mantenimiento de los tratamientos previos, el ahorro total durante el periodo de observación fue de 169.107,31 (Euro). CONCLUSIONES: Dimetilfumarato y teriflunomida, además de aportar nuevas alternativas terapéuticas, no solo no han supuesto un incremento sino, por el contrario, una disminución en los costes del tratamiento de la EM en nuestro hospital

INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. RESULTS: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of (Euro)169,107.31 over the study period. CONCLUSIONS: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital

Incorporating patients' preferences in the value assessment of disease-modifying therapies for multiple sclerosis: a narrative review.

Introduction: Despite the increasing role of patients in the US healthcare system, patients have yet been engaged in the value assessment of their treatments, including disease-modifying therapies (DMTs) for multiple sclerosis (MS). The objectives of this review were therefore to summarize existing studies on cost-effectiveness analysis (CEA) with quality-adjusted life years (QALYs) and patients' preferences of DMTs for MS, and to discuss how to incorporate patients' preferences into the value assessment of DMTs.Area covered: We reviewed previous systematic reviews and conducted further search until November 2020 for studies on CEA with QALYs and patients' preferences of DMTs for MS. We identified the outcomes that were assessed or valued in the CEA studies and the DMT attributes that were important to patients with MS.Expert opinion: Our literature review showed that the studies using CEA with QALYs failed to capture some important DMT attributes, e.g., route and frequency of administration, identified in the studies on the patients' preferences. Various approaches were available for incorporating the patients' preferences in the value assessment of DMTs for MS. We supported this incorporation, which subsequently would increase patient access to preferred DMTs.

Factors associated with the healthcare expenditures of patients with multiple sclerosis in urban areas of China estimated by a generalized estimating equation.

Background: Multiple sclerosis (MS) has a significant healthcare burden. This study examined the medical cost and out-of-pocket (OOP) expenses, and quantified the impact factors contributing to the costs. Methods: This is a retrospective study in 77 Chinese urban cites from 2013 to 2015. The data included the details of the utilization of medical resources, cost, and reimbursement ratio of all patients with a diagnosis of MS. A generalized estimating equation model was used to estimate the factors influencing the direct medical cost and OOP expenses for in- and outpatients. Results: A total of 267 patients with MS were identified. The mean cost per in- and outpatient was respectively 16996.2 and 2294.2 renminbi ($2768.12 and $373.65, €2087.16 and €281.73). Approximately 27% of the expenses were paid by the patients OOP. Factors contributing to high cost and high OOP expenses for inpatients were tertiary hospital admission, length of stay and residence in the east regions of China. Females and outpatients with resident insurance paid more OOP. Conclusion: This study illustrates the medical costs and burden of MS in Chinese patients and provides real-world data on MS that are essential for the improvement of health policies.

Telerehabilitation benefits patients with multiple sclerosis in an urban setting.

INTRODUCTION: People living with multiple sclerosis (MS) often require rehabilitation to manage their symptoms. Telerehabilitation offers improved access to treatment options by reducing travel time and cost. Our telerehabilitation program pairs training exercises simultaneously with transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique. In the current study, we characterized the benefits of our remotely supervised tDCS (RS-tDCS) at-home telerehabilitation protocol in an urban sample of MS participants. METHODS: Participants with MS were recruited to complete a telerehabilitation trial using tDCS paired with cognitive rehabilitation at-home using remote supervision (RS-tDCS). Participant time and travel costs for study visits to our clinic in midtown New York City were calculated. RESULTS: Forty-four patients with MS (aged 18 to 71) with mild to severe neurologic disability (Expanded Disability Status Scale score median = 3.5, range: 0.0 to 8.0) completed the survey. Round-trip clinic attendance required 2.3 ± 2.3 h and US $27.04 ± 38.13 for out-of-pocket expenses. Participants rated difficulty of clinic attendance as moderately to significantly difficult (2.5 ± 1.3). Severity of neurologic disability accounted for the greatest variance in difficulty attending clinic (30%, p < 0.001). RS-tDCS had 95% treatment compliance and 93% of participants reported satisfaction with the at-home treatment. DISCUSSION: Attending clinic is associated with significant costs for patients with neurologic disorders, even in urban settings. Rehabilitation can be delivered at home and supervised in real-time via videoconference.

A Systematic Review of the Incidence, Prevalence, Costs, and Activity and Work Limitations of Amputation, Osteoarthritis, Rheumatoid Arthritis, Back Pain, Multiple Sclerosis, Spinal Cord Injury, Stroke, and Traumatic Brain Injury in the United States: A 2019 Update.

OBJECTIVES: To present recent evidence on the prevalence, incidence, costs, activity limitations, and work limitations of common conditions requiring rehabilitation. DATA SOURCES: Medline (PubMed), SCOPUS, Web of Science, and the gray literature were searched for relevant articles about amputation, osteoarthritis, rheumatoid arthritis, back pain, multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury. STUDY SELECTION: Relevant articles (N=106) were included. DATA EXTRACTION: Two investigators independently reviewed articles and selected relevant articles for inclusion. Quality grading was performed using the Methodological Evaluation of Observational Research Checklist and Newcastle-Ottawa Quality Assessment Form. DATA SYNTHESIS: The prevalence of back pain in the past 3 months was 33.9% among community-dwelling adults, and patients with back pain contribute $365 billion in all-cause medical costs. Osteoarthritis is the next most prevalent condition (approximately 10.4%), and patients with this condition contribute $460 billion in all-cause medical costs. These 2 conditions are the most prevalent and costly (medically) of the illnesses explored in this study. Stroke follows these conditions in both prevalence (2.5%-3.7%) and medical costs ($28 billion). Other conditions may have a lower prevalence but are associated with relatively higher per capita effects. CONCLUSIONS: Consistent with previous findings, back pain and osteoarthritis are the most prevalent conditions with high aggregate medical costs. By contrast, other conditions have a lower prevalence or cost but relatively higher per capita costs and effects on activity and work. The data are extremely heterogeneous, which makes anything beyond broad comparisons challenging. Additional information is needed to determine the relative impact of each condition.

A literature review of cost-of-illness studies on the economic burden of multiple sclerosis.

BACKGROUND: Multiple sclerosis has both high healthcare and social impacts. OBJECTIVE: The purpose of this article is to analyse the available literature describing the economic burden of multiple sclerosis and to compare costs among studies examining main cost drivers. METHODS: A literature search on studies published in English on cost-of-illness of multiple sclerosis included in this review using PubMed, the Cochrane Library, SCOPUS and Web of Science includes a retrospective horizon and it describes direct and indirect costs in patients categorized into severity groups. RESULTS: Several papers were obtained from the database search (n=37). Additionally, results from "hand searching" were also included, where a wider horizon was considered. Cost estimates were compared among studies that used a societal perspective on costs, time-period studied, and year of price level used. The estimated total annual cost per patient in Europe is on average 40,300€ (n=20). In addition, differences by geographic areas and severity groups are also considered. All in all, the higher the severity, the higher the associated costs. CONCLUSIONS: This systematic review provides one clear finding: multiple sclerosis places a huge economic burden on healthcare models and societies due to productivity losses and caregiver burden. Moreover, costs of drugs were main cost determinants for less severe cases of multiple sclerosis and informal care and production losses for the most severe cases of multiple sclerosis.

Real-World Evidence on the Societal Economic Relapse Costs in Patients with Multiple Sclerosis.

BACKGROUND: Relapses are the hallmark of multiple sclerosis (MS). Analyses have shown that the cost of MS increases during periods of relapse. However, results are inconsistent between studies, possibly due to different study designs and the different implications of relapses with respect to patient characteristics. OBJECTIVES: The aims were to estimate and describe direct and indirect relapse costs and to determine differences in costs with respect to patient characteristics. Furthermore, we describe the pharmacoeconomic impact during the relapse follow-up. METHODS: Data were extracted from two German, multicenter, observational studies applying a validated resource costs instrument. Relapse costs were calculated as the difference in quarterly costs between propensity score (PS)-matched patients with and without relapses (1:1 ratio). For relapse active patients, we additionally calculated the difference between quarterly costs prior to and during relapse and determined costs in the post-relapse quarter. RESULTS: Of 1882 patients, 607 (32%) presented at least one relapse. After PS-matching, 597 relapse active and relapse inactive patients were retained. Relapse costs (in 2019 values) ranged between €791 (age 50 + years) and €1910 (disease duration < 5 years). In mildly disabled and recently diagnosed patients, indirect relapse costs (range €1073-€1207) constantly outweighed direct costs (range €591-€703). The increase from prior quarter to relapse quarter was strongest for inpatient stays (+ 366%, €432; p < 0.001), day admissions (+ 228%, €57; p < 0.001), and absenteeism (127%, €463; p < 0.001). In the post-relapse quarter, direct costs and costs of absenteeism remained elevated for patients with relapse-associated worsening. CONCLUSION: A recent diagnosis and mild disability lead to high relapse costs. The results suggest the necessity to incorporate patient characteristics when assessing relapse costs.

The fiscal consequences of public health investments in disease-modifying therapies for the treatment of multiple sclerosis in Sweden.

Background and aims: The economic consequences of multiple sclerosis (MS) are broader than those observed within the health system. The progressive nature suggests that people will not be able to live a normal productive life and will gradually require public benefits to maintain living standards. This study investigates the public economic impact of MS and how investments in disease-modifying therapies (DMTs) influence the lifetime costs to government attributed to changes in lifetime tax revenue and disability benefits based on improved health status linked to delayed disease progression.Methods: Disease progression rates from previous MS Markov cohort models were applied to interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab using a public economic framework. The established relationship between expanded disability status scale and work-force participation, annual earnings, and disability rates for each DMT were applied. Subsequently, we assessed the effect of DMTs on discounted governmental costs consisting of health service costs, social insurance and disability costs, and changes in lifetime tax revenues.Results: Fiscal benefits attributed to informal care and community services savings for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were SEK340,387, SEK486,837, SEK257,330, and SEK958,852 compared to placebo, respectively. Tax revenue gains linked to changes in lifetime productivity for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were estimated to be SEK27,474, SEK39,659, SEK21,661, and SEK75,809, with combined fiscal benefits of cost savings and tax revenue increases of SEK410,039, SEK596,592, SEK326,939, and SEK1,208,023, respectively.Conclusion: The analysis described here illustrates the broader public economic benefits for government attributed to changes in disease status. The lifetime social insurance transfer costs were highest in non-treated patients, and lower social insurance costs were demonstrated with DMTs. These findings suggest that focusing cost-effectiveness analysis only on health costs will likely underestimate the value of DMTs.

Marginal Health Care Expenditure Burden Among U.S. Civilian Noninstitutionalized Individuals with Multiple Sclerosis: 2010-2015.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disorder with significant health care burden. However, little is known about health care expenditures since the introduction of oral agents for MS after 2010. OBJECTIVE: To analyze health care expenditures in individuals with MS using Medical Expenditure Panel Survey (MEPS) data from 2010-2015. METHODS: This retrospective cross-sectional study included adults (≥ 18 years) with MS (Clinical Classification Code 080) and those without MS based on the 2010-2015 full year consolidated MEPS Household Component and Medical Provider Component data files. Descriptive weighted analyses were performed to compare health care expenditures between individuals with MS and without MS. The 2-part model involving probit and generalized linear models was used to estimate the marginal increase in total health care expenditures for MS patients. RESULTS: There were 0.61 million patients (95% CI = 0.50-0.72) diagnosed with MS annually, accounting for a prevalence of 0.25%. The 2-part model revealed that the marginal total health care expenditures in patients diagnosed with MS were $20,103.49 (95% CI = $14,516.24-$25,690.73) more compared with those without MS. Further, the mean adjusted prescription medication expenditures for the MS group were $13,092.16 (95% CI = $9,452.20-$16,732.12) higher than the non-MS group and accounted for 65.12% of total health care expenditures in MS. CONCLUSIONS: MS is an expensive neuroinflammatory disease with a majority of the burden attributable to prescription medications. High prescription expenditure burden can be a barrier to optimal patient care in MS. DISCLOSURES: No funding was received for this study. Hutton reports grants from Adamas, Biogen, EMD Serono, Genzyme, Hoffman-LaRoche, MedImmune, Mallinckrodt, and Novartis and fees from Biogen, Celgene, Genzyme, Genentech, and Novartis, outside the submitted work. Aparasu reports grants from Novartis, Incyte, and Astellas, outside the submitted work. Earla and Thornton have nothing to disclose. Part of the study findings was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 National Conference; May 18-22, 2019; New Orleans, LA.

Economic costs incurred by the patients with multiple sclerosis at different levels of the disease: a cross-sectional study in Northwest Iran.

BACKGROUND: Multiple sclerosis (MS) causes significant economic burden to the patients, families, health systems and society. This study aimed to estimate the annual economic costs incurred by patients with multiple sclerosis (pwms) at different levels of the disease. METHOD: This was a cross-sectional study, using the Expanded Disability Status Scale (EDSS) tool for assessing the disease level of 300 (=N) pwms in East Azerbaijan province, Iran. To estimate the cost of MS, a questionnaire with its validity and reliability (CVR 92% and CVI 87%) and pilot test (Cronbach's alpha score 0.89) was used. The data were collected by interviewing pwms and reviewing their clinical records. Multivariate linear regression was used to assess the relationship between disease levels and incurred costs. RESULTS: The results revealed that the mean annual cost for pwms in Iran is 97,521,740 IRR (equivalent to 2321.94 USD; 1978.93 EURO) and the mean score of EDSS in pwms was 3.14. The annual cost incurred by pwms with mild, moderate and severe levels of disease were 83,918,150 IRR (1998.05 USD; 1702.88EURO), 137,772,660 IRR (3280.30 USD; 2795.71 EURO) and 119,962,670 IRR (2856.25 USD;2434.30 EURO), respectively. Also, on average, each increase in EDSS score in pwms in Iran led to increase 8,139,260 IRR (equivalent to 193.79 USD; and 165.16 EURO) in total annual cost which must paid from pwms and their households exclusively. Also, there was a significant relationship between total annual cost and disease severity in such a way that any increase in EDSS degree is led to 8,139,260 IRR (193.79 USD; 165.16 EURO) added cost for pwms. CONCLUSION: The study results could be helpful for Iranian health managers to solve problems which are facing by the patients with multiple sclerosis and their families.

Terapias modificadoras de la enfermedad en esclerosis múltiple: revisión sistemática de costo-efectividad / Disease modifying therapies in multiple sclerosis: cost-effectiveness systematic review

OBJETIVO: Identificar y describir los estudios de costo-efectividad que evalúan las terapias modificadoras de la enfermedad en esclerosis múltiple recurrente-remitente. MÉTODO: Revisión sistemática de la literatura en MEDLINE, Embase, Cochrane Library, LILACS, Tufts Medical Center cost-effectiveness analysis registry, National Health Service economic evaluation database y Open Grey; búsqueda limitada entre enero de 2010 y diciembre de 2017, se ejecutó en enero de 2018. Se incluyeron modelos de costo-efectividad con perspectiva de pagador para interferón beta-1a, interferón beta-1b, acetato de glatiramero, teriflunomida, fingolimod, dimetilfumarato, natalizumab, alemtuzumab y rituximab. La herramienta Quality of Health Economic Studies fue usada para determinar la calidad de los estudios, el sesgo se evaluó sin una herramienta estandarizada, dada su no existencia. Se analizaron costos directos, años de vida ajustados por calidad y la razón de costo-efectividad incremental. La extracción de los datos y la evaluación de la información se realizaron por cada autor de forma independiente Resultados: Se encontraron 401 referencias, se incluyeron nueve estudios; hubo variabilidad en múltiples aspectos metodológicos. Según la razón de costo-efectividad incremental (costo), dos trabajos mostraron que ninguna terapia de primera línea fue costo-efectiva, un tercer estudio reporta al interferón beta-1b como dominante sobre placebo (-315.109,45 dólar estadounidense [US$]) y un cuarto artículo expone a teriflunomida como dominante sobre interferones y acetato de glatiramero (-121.840,37 US$). Respecto a las terapias de segunda línea, dimetil fumarato fue costo-efectivo en un estudio comparado con acetato de glatiramero e interferón beta-1a y fue dominante en otro trabajo frente a acetato de glatiramero (-158.897,93 US$) y fingolimod (-92.988,97 US$). En la tercera línea de tratamiento, natalizumab fue costo-efectivo sobre fingolimod en un artículo, y alemtuzumab fue dominante contra fingolimod (-49.221 US$) en un segundo estudio. En un tercer ensayo el alemtuzumab fue dominante sobre natalizumab (-1.656.266,07 US$). Muchos estudios tuvieron sesgo de patrocinador. Ocho artículos obtuvieron alta puntuación de calidad con la herramienta Quality of Health Economic Studies. CONCLUSIONES: Este trabajo demuestra que existe una gran variabilidad metodológica entre los estudios de costo-efectividad, y algunos de ellos tienen resultados contradictorios. No es posible determinar qué terapia modificadora de la enfermedad en esclerosis múltiple recurrente-remitente es costo-efectiva

OBJECTIVE: To identify and describe cost-effectiveness studies that eva-luate disease modifying therapies in the context of relapsing-remitting mul-tiple sclerosis. METHOD: A systematic review of the literature was carried out by searching MEDLINE, Embase, the Cochrane Library, LILACS, the Tufts Medical Center Cost-Effectiveness Analysis Registry, the National Health Service Economic Evaluation Database and Open Grey. The search was performed in January 2018 and covered articles published between January 2010 and December 2017. The studies reviewed were payer-perspective cost-effectiveness analy-ses for interferon beta-1a, interferon beta-1b, glatiramer acetate, teriflunomide, fingolimod, dimethyl fumarate, natalizumab, alemtuzumab and rituximab. The Quality of Health Economic Studies instrument was used to determine the quality of the studies reviewed. Risk of bias was assessed without a standardized tool. An analysis was made of direct costs, quality-adjusted life-years and the incremental cost-effectiveness ratio. Data extraction and evaluation of information were conducted separately by each author. RESULTS: Four hundred one references were found; nine studies were included. A great degree of variability was identified for several methodological aspects. Two studies that applied the incremental cost-effectiveness ratio (cost) showed no first-line therapy to be cost-effective. A third study demonstrated dominance of interferon beta-1b over placebo (USD -315,109.45) and a fourth paper showed dominance of teriflu-nomide over interferons and glatiramer acetate (USD -121,840.37). As regards second-line therapies, dimethyl fumarate was cost-effective in a study that compared it to glatiramer acetate and interferon beta-1a and it was dominant in another study that compared it with glatiramer acetate (USD -158,897.93) and fingolimod (USD -92,988.97). In the third line of treatment, one study showed natalizumab to be cost-effective as compared with fingolimod, and another study showed alemtuzumab to be dominant over fingolimod (USD -49,221). A third trial demonstrated alemtuzumab to be dominant over natalizumab (USD -1,656,266.07). Many of the trials have sponsorship bias. Eight of the trials received a high QHES score. CONCLUSIONS: The present paper shows that cost-effectiveness studies have high levels of methodological variability, some of them reaching contradictory results. As a result, it is not possible to determine which disease-modifying therapy is really cost-effective in the context of relapsing-remitting multiple sclerosis

Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial.

BACKGROUND: Cognitive difficulties experienced by people with multiple sclerosis (MS) impact their quality of life and daily functioning, from childcare and work, to social and self-care activities. Despite the high prevalence of cognitive difficulties seen in MS, there is a lack of developed programmes that target cognition, while also supporting patients by helping them to function well in everyday life. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention. It addresses the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the current research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. The focus is on feasibility outcomes as well as functioning associated with cognitive difficulty and secondary outcomes related to cognition, fatigue and quality of life. METHODS: One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment as usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The primary outcome measure is the goal attainment scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention and at 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants' perspectives will also be examined as part of the feasibility study. DISCUSSION: Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. In the event that results indicate efficacy, study findings will suggest that COB-MS requires consideration as a means of enhancing cognitive and daily functioning in people living with MS. TRIAL REGISTRATION: ISRCTN: ISRCTN11462710. Registered on 9 September 2019.

Social value of a set of proposals for the ideal approach of multiple sclerosis within the Spanish National Health System: a social return on investment study.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients' lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create. METHODS: A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies. RESULTS: The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million € and social return to 272 million €, so each euro invested could yield almost €2 of social return. CONCLUSIONS: This study could guide health interventions, resulting in money savings for the SNHS and increases in patients' quality of life.

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.

Impact of multiple sclerosis phenotypes on burden of disease in Finland.

Aims: The aim of this study was to quantify how multiple sclerosis (MS) phenotypes differ from each other in respect of costs and quality-of-life.Materials and methods: The study is based on survey data from Finnish patients with MS (n = 553). The information contained disease type, disease severity according to self-reported Expanded Disease Severity Scale (EDSS), healthcare resource use, and medication use. In addition, information related to employment and early retirement was collected. EQ-5D-VAS and Multiple Sclerosis Impact Scale-29 (MSIS-29) instruments were used to collect quality-of-life data, and Fatigue Severity Scale (FSS) instrument for evaluating fatigue. Patients were stratified based on their disease type (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS)) and disease severity. The data were primarily analyzed using summary statistics.Results: SPMS had the highest annual total cost (71,177€) followed by PPMS (51,082€) and RRMS (36,492€). Early retirement covered the greatest share of costs in RRMS (39%) and SPMS (43%). In PPMS, early retirement and professional care were the two most equally important cost drivers, contributing together 56% of the total costs. Direct healthcare costs were responsible for 33%, 19%, and 18% of total costs in RRMS, SPMS, and PPMS. The mean EDSS in RRMS, SPMS, and PPMS were 2.5, 5.5, and 5.9, respectively. Differences in the quality-of-life were observed with both disease specific (MSIS-29) and generic (EQ-5D-VAS) instruments. The mean utility value from EQ-5D among patients with RRMS, SPMS, and PPMS was 0.76, 0.52, and 0.49, respectively. In addition, patients with SPMS and PPMS were more likely to report fatigue than patients with RRMS.Conclusions: MS phenotype has an impact on costs and quality-of-life of the patients. Early retirement seems to be one of the most important contributors to MS-related costs.