RESUMEN
BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/psicología , Adulto , Estudios Retrospectivos , EspañaRESUMEN
OBJECTIVE: To identify and describe cost-effectiveness studies that evaluate disease modifying therapies in the context of relapsing- remitting multiple 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 analyses 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 teriflunomide 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 relapsingremitting multiple sclerosis.
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 costoefectivo 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.
Asunto(s)
Antirreumáticos/economía , Antirreumáticos/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/economía , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Análisis Costo-Beneficio , Humanos , Inmunosupresores/uso terapéutico , Años de Vida Ajustados por Calidad de VidaRESUMEN
DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Synnott and Pearson are employed by ICER. Bloudek and Carlson report a research agreement between the University of Washington and ICER; Bloudek reports consulting fees from Allergan, Seattle Genetics, Dermira, Sunovion, TerSera Therapeutics, Cook Regentech, and Mallinckrodt Pharmaceuticals; and Carlson reports personal fees from Bayer, unrelated to this report. Sharaf reports consulting fees from ICER.
Asunto(s)
Azetidinas/uso terapéutico , Compuestos de Bencilo/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Azetidinas/economía , Compuestos de Bencilo/economía , Análisis Costo-Beneficio , Humanos , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Moduladores de los Receptores de fosfatos y esfingosina 1/economía , Resultado del TratamientoRESUMEN
DISCLOSURES: No funding supported the writing of this commentary. The author has nothing to disclose.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Azetidinas/economía , Azetidinas/uso terapéutico , Compuestos de Bencilo/economía , Compuestos de Bencilo/uso terapéutico , Aprobación de Drogas/legislación & jurisprudencia , Humanos , Esclerosis Múltiple Crónica Progresiva/economía , Atención Dirigida al Paciente/economía , Apoyo a la Investigación como Asunto/economíaRESUMEN
Ocrelizumab is indicated for relapsing remitting and primary progressive multiple sclerosis (RRMS and PPMS, respectively). In an appraisal undertaken by the National Institute for Health and Care Excellence (NICE), the company Roche presented the evidence for ocrelizumab used in patients with PPMS, which came from one single randomised controlled trial (RCT) comparing ocrelizumab versus placebo. Based on results from this trial, the licensed indication was restricted to patients with early PPMS in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity. Overall, the Evidence Review Group (ERG) found that the RCT had a low risk of bias. In the post-hoc defined magnetic resonance imaging (MRI) active subgroup, matching the label indication, the risk of confirmed disability progression sustained for 12 weeks (CDP-12) was significantly delayed in the ocrelizumab group compared to placebo. However, considering the same risk with progression sustained for 24 weeks (CDP-24), which was deemed the most clinically relevant, the benefit from ocrelizumab did not reach statistical significance. In the same MRI active subgroup, benefits from ocrelizumab on functional outcomes and on health-related quality of life were not clearly demonstrated. A de novo Markov model was used to estimate the cost-effectiveness of ocrelizumab versus best supportive care (BSC) for treating patients with PPMS. Health states were defined by the Expanded Disability Status Scale (EDSS), ranging from 0 to 9. Disability progression was based on the MSBase natural history cohort that exhibited disease progression in the absence of disease-modifying therapy. Treatment with ocrelizumab delayed disability progression, with evidence of its clinical effectiveness obtained from the RCT. The economic analysis was undertaken from the National Health Service and Personal Social Services perspective, and the outcomes were reported in terms of life years gained and quality-adjusted life years (QALYs), with the overall results reported in terms of an incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained over a 50-year time horizon. Both costs and effects were discounted at 3.5% per annum. The company undertook deterministic one-way sensitivity analyses and scenario analyses, including probabilistic sensitivity analysis (PSA). The ERG raised several concerns, which were discussed at the appraisal committee meetings, resulting in the committee's preferences being applied and a revised economic analysis from the company. Under an approved patient access scheme with appraisal committee preferences applied, analyses yielded an ICER of approximately £78,300 per QALY. Sensitivity analysis results indicated that the treatment effect on CDP-12 had the greatest impact. Results for the PSA showed that at a willingness-to-pay threshold of £30,000 per QALY gained, ocrelizumab versus BSC had a zero probability of being cost-effective. Following new analyses submitted by the company, with a revised confidential patient access scheme, NICE recommended ocrelizumab in the treatment of early PPMS in adults with imaging features characteristic of inflammatory activity.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales Humanizados/economía , Análisis Costo-Beneficio , Progresión de la Enfermedad , Humanos , Factores Inmunológicos/economía , Esclerosis Múltiple Crónica Progresiva/economía , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Estatal , Evaluación de la Tecnología BiomédicaRESUMEN
BACKGROUND: People severely impaired with progressive multiple sclerosis spend much of their day sitting, with very few options to improve motor function. As a result, secondary physical and psychosocial complications can occur. Effective and feasible self-management strategies are needed to reduce sedentary behaviour and enhance motor function. In this study, we aimed to assess the clinical and cost effectiveness of a home-based, self-managed, standing frame programme. METHODS: SUMS was a pragmatic, multicentre, randomised controlled superiority trial of people with progressive multiple sclerosis and severe mobility impairment, undertaken in eight centres from two regions in the UK. The study had assessor-blinded outcome assessments with use of clinician-rated and patient-rated measures at baseline, 20 weeks, and 36 weeks. After baseline assessment, participants were randomised (1:1) by computer-generated assignment to either a standing frame programme plus usual care or usual care alone. The intervention consisted of two home-based physiotherapy sessions (60 min each) to set up the standing frame programme, supported by six follow-up telephone calls (15 min per call). Participants were asked to stand for 30 min, three times per week over 20 weeks, and encouraged to continue in the longer term, although no further physiotherapy support was provided. The primary clinical outcome was motor function measured by the Amended Motor Club Assessment (AMCA) score at week 36, analysed in the modified intention-to-treat population (excluding only patients who were deemed ineligible after randomisation, those who withdrew from the trial and were unwilling for their previously collected data to be used, or those who did not provide baseline and week 36 measurements). A 9-point AMCA score change was considered clinically meaningful a priori. Adverse events were collected through a daily preformatted patient diary throughout the 36 weeks and analysed in the modified intention-to-treat population. An economic assessment established the resources required to provide the standing frame programme, estimated intervention costs, and estimate cost effectiveness. This trial is registered with the International Standard Randomised Controlled Trials, number ISRCTN69614598. FINDINGS: Between Sept 16, 2015, and April 28, 2017, 285 people with progressive multiple sclerosis were screened for eligibility, and 140 were randomly assigned to either the standing frame group (n=71) or the usual care group (n=69). Of these, 122 completed the primary outcome assessment (61 participants in both groups) for the modified intention-to-treat analysis. The use of the standing frame resulted in a significant increase in AMCA score compared with that for usual care alone, with a fully adjusted between-group difference in AMCA score at 36 weeks of 4·7 points (95% CI 1·9-7·5; p=0·0014). For adverse events collected through patient diaries, we observed a disparity between the two groups in the frequency of short-term musculoskeletal pain (486 [41%] of 1188 adverse events in the standing frame group vs 160 [22%] of 736 adverse events in the usual care group), which was potentially related to the intervention. The musculoskeletal pain lasted longer than 7 days in five participants (two in the standing frame group and three in the usual care group). No serious adverse events related to the study occurred. The standing frame group had a mean 0·018 (95% CI -0·014 to 0·051) additional quality-adjusted life-years (QALYs) compared with those of the usual care group, and the estimated incremental cost-per-QALY was approximately £14â700. INTERPRETATION: The standing frame programme significantly increased motor function in people with severe progressive multiple sclerosis, although not to the degree that was considered a priori as clinically meaningful. The standing frame is one of the first physiotherapy interventions to be effective in this population. We suggest that the programme is feasible as a home-based, self-managed intervention that could be routinely implemented in clinical practice in the UK. FUNDING: UK National Institute of Health Research.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva/rehabilitación , Modalidades de Fisioterapia/economía , Automanejo/economía , Anciano , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/economía , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Several disease-modifying therapies (DMTs) treat relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Few comprehensive cost-effectiveness analyses exist in this area, particularly from a payer perspective, despite rapidly increasing prices of DMTs. OBJECTIVE: We aimed to systematically compare cost effectiveness of all relevant DMTs for first-line treatment of RRMS, second-line treatment of RRMS, and first-line treatment of PPMS. METHODS: We used a Markov model with health states based on Expanded Disability Status Score categories. Upon discontinuing first-line treatment, RRMS patients continued to second-line therapy then to supportive care, and PPMS patients moved directly to supportive care. Data was sourced from clinical trials and commercially and publicly available sources. The target population was treatment-naïve adults with RRMS or PPMS. We used a lifetime horizon from a US payer perspective, and compared DMTs for RRMS (first-line: dimethyl fumarate, glatiramer acetate, interferon ß-1a, interferon ß-1b, peginterferon ß-1a, teriflunomide, natalizumab, fingolimod, and ocrelizumab; second-line: alemtuzumab, natalizumab, fingolimod, and ocrelizumab), ocrelizumab for PPMS, and supportive care. Outcome measures included total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: For RRMS first-line therapy, ocrelizumab dominated the other DMTs with an ICER of US$166,338/QALY compared with supportive care. For RRMS second-line therapy, alemtuzumab dominated the other three DMTs, providing more QALYs for lower costs. For PPMS, ocrelizumab had an ICER of US$648,799/QALY compared with supportive care. Wide variability in results was observed in the probabilistic sensitivity analysis. Results were sensitive to the relative risk of progression and cost of DMTs. CONCLUSIONS: Ocrelizumab would likely be cost effective as a first-line treatment for RRMS with a discounted price but was not cost effective for PPMS. Alemtuzumab dominated other options for second-line treatment of RRMS. Other DMTs were generally similar in terms of costs and health outcomes, providing health benefits compared to supportive care but with significant added costs. If drug prices were lowered, more DMTs could be cost effective.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/terapia , Esclerosis Múltiple Recurrente-Remitente/economía , Esclerosis Múltiple Recurrente-Remitente/terapia , Análisis Costo-Beneficio , Citocinas/metabolismo , Femenino , Humanos , Masculino , Cadenas de Markov , Resultado del Tratamiento , Adulto JovenRESUMEN
Epidemiological data on primary progressive multiple sclerosis (PPMS) are scarce. This study was aimed to evaluate the burden of PPMS in Italy with healthcare resources utilisation and costs for Italian National Health System (INHS). A 2-year cross-sectional analysis of real-world data collected in the ARCO database, covering > 10 million Italian inhabitants, was performed. From a cohort of patients affected by MS in 2014, those supposedly affected by PPMS were defined by the concurrent matching of absence of disease-modifying treatments and use of rehabilitation services. Any other drug prescriptions, outpatient services and hospitalisations were analysed in 2015 for each subject. The average annual cost per patient was provided both for each expenditure item and by integrating these. Of 13,253,591 inhabitants, 18,453 resulted affected by MS (prevalence 139 × 100,000). Of these, 1849 agreed with additional criteria to identify PPMS (10% of MS population). The 26.8% of these experienced at least one admission in 1 year, 97.3% used at least one outpatient service and 94.3% received at least one reimbursed drug. In the perspective of INHS, PPMS generated an average annual cost of 3783 per person: 49% for hospitalisations, 28% for outpatient services and 23% for drugs. This study provides a reliable estimation of the PPMS burden in Italy, in terms of healthcare utilisation and direct costs. These findings could be useful to estimate the changes in health expenditure following the incoming of new drugs to treat PPMS with increase of pharmaceutical cost and potential decrease of rehabilitation and hospitalisation costs.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/terapia , Aceptación de la Atención de Salud , Adulto , Estudios de Cohortes , Costo de Enfermedad , Estudios Transversales , Femenino , Costos de la Atención en Salud , Humanos , Italia/epidemiología , Masculino , Esclerosis Múltiple Crónica Progresiva/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS. OBJECTIVES: There were three objectives in the CUPID study: (1) to evaluate whether or not Δ(9)-THC could slow the course of progressive MS; (2) to assess the long-term safety of Δ(9)-THC; and (3) to explore newer ways of conducting clinical trials in progressive MS. DESIGN: The CUPID trial was a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were randomised in a 2 : 1 ratio to Δ(9)-THC or placebo. Randomisation was balanced according to Expanded Disability Status Scale (EDSS) score, study site and disease type. Analyses were by intention to treat, following a pre-specified statistical analysis plan. A cranial magnetic resonance imaging (MRI) substudy, Rasch measurement theory (RMT) analyses and an economic evaluation were undertaken. SETTING: Twenty-seven UK sites. PARTICIPANTS: Adults aged 18-65 years with primary or secondary progressive MS, 1-year evidence of disease progression and baseline EDSS 4.0-6.5. INTERVENTIONS: Oral Δ(9)-THC (maximum 28 mg/day) or matching placebo. ASSESSMENT VISITS: Three and 6 months, and then 6-monthly up to 36 or 42 months. MAIN OUTCOME MEASURES: Primary outcomes were time to EDSS progression, and change in Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) 20-point physical subscale (MSIS-29phys) score. Various secondary patient- and clinician-reported outcomes and MRI outcomes were assessed. RMT analyses examined performance of MS-specific rating scales as measurement instruments and tested for a symptomatic or disease-modifying treatment effect. Economic evaluation estimated mean incremental costs and quality-adjusted life-years (QALYs). RESULTS: Effectiveness - recruitment targets were achieved. Of the 498 randomised patients (332 to active and 166 to placebo), 493 (329 active and 164 placebo) were analysed. PRIMARY OUTCOMES: no significant treatment effect; hazard ratio EDSS score progression (active : placebo) 0.92 [95% confidence interval (CI) 0.68 to 1.23]; and estimated between-group difference in MSIS-29phys score (active-placebo) -0.9 points (95% CI -2.0 to 0.2 points). Secondary clinical and MRI outcomes: no significant treatment effects. Safety - at least one serious adverse event: 35% and 28% of active and placebo patients, respectively. RMT analyses - scale evaluation: MSIS-29 version 2, MS Walking Scale-12 version 2 and MS Spasticity Scale-88 were robust measurement instruments. There was no clear symptomatic or disease-modifying treatment effect. Economic evaluation - estimated mean incremental cost to NHS over usual care, over 3 years £27,443.20 per patient. No between-group difference in QALYs. CONCLUSIONS: The CUPID trial failed to demonstrate a significant treatment effect in primary or secondary outcomes. There were no major safety concerns, but unwanted side effects seemed to affect compliance. Participants were more disabled than in previous studies and deteriorated less than expected, possibly reducing our ability to detect treatment effects. RMT analyses supported performance of MS-specific rating scales as measures, enabled group- and individual person-level examination of treatment effects, but did not influence study inferences. The intervention had significant additional costs with no improvement in health outcomes; therefore, it was dominated by usual care and not cost-effective. Future work should focus on determining further factors to predict clinical deterioration, to inform the development of new studies, and modifying treatments in order to minimise side effects and improve study compliance. The absence of disease-modifying treatments in progressive MS warrants further studies of the cannabinoid pathway in potential neuroprotection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN62942668. FUNDING: The National Institute for Health Research Health Technology Assessment programme, the Medical Research Council Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society and Multiple Sclerosis Trust. The report will be published in full in Health Technology Assessment; Vol. 19, No. 12. See the NIHR Journals Library website for further project information.
Asunto(s)
Análisis Costo-Beneficio , Dronabinol/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , Administración Oral , Adulto , Progresión de la Enfermedad , Método Doble Ciego , Dronabinol/administración & dosificación , Dronabinol/efectos adversos , Dronabinol/economía , Femenino , Financiación Gubernamental , Financiación Personal , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/psicología , Espasticidad Muscular/clasificación , Neuroimagen/métodos , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Factores de Tiempo , Reino UnidoRESUMEN
BACKGROUND: Exercise is a safe, non-pharmacological adjunctive treatment for people with multiple sclerosis but cost-effective approaches to implementing exercise within health care settings are needed. OBJECTIVE: The objective of this paper is to assess the cost effectiveness of a pragmatic exercise intervention in conjunction with usual care compared to usual care only in people with mild to moderate multiple sclerosis. METHODS: A cost-utility analysis of a pragmatic randomised controlled trial over nine months of follow-up was conducted. A total of 120 people with multiple sclerosis were randomised (1:1) to the intervention or usual care. Exercising participants received 18 supervised and 18 home exercise sessions over 12 weeks. The primary outcome for the cost utility analysis was the incremental cost per quality-adjusted life year (QALY) gained, calculated using utilities measured by the EQ-5D questionnaire. RESULTS: The incremental cost per QALY of the intervention was £10,137 per QALY gained compared to usual care. The probability of being cost effective at a £20,000 per QALY threshold was 0.75, rising to 0.78 at a £30,000 per QALY threshold. CONCLUSION: The pragmatic exercise intervention is highly likely to be cost effective at current established thresholds, and there is scope for it to be tailored to particular sub-groups of patients or services to reduce its cost impact.
Asunto(s)
Terapia por Ejercicio/economía , Costos de la Atención en Salud , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/terapia , Esclerosis Múltiple Recurrente-Remitente/economía , Esclerosis Múltiple Recurrente-Remitente/terapia , Adulto , Análisis Costo-Beneficio , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Económicos , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Años de Vida Ajustados por Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Fatigue is a common and troubling symptom for people with multiple sclerosis (MS). AIM: To evaluate the effectiveness and cost-effectiveness of a six-session group-based programme for managing MS-fatigue (Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle (FACETS)). METHODS: Three-centre parallel arm randomised controlled trial with economic evaluation. Patients with MS and significant fatigue were randomised to FACETS plus current local practice (FACETS) or current local practice alone (CLP), using concealed computer-generated randomisation. Participant blinding was not possible. Primary outcomes were fatigue severity (Fatigue Assessment Instrument), self-efficacy (Multiple Sclerosis-Fatigue Self-Efficacy) and disease-specific quality of life (Multiple Sclerosis Impact Scale (MSIS-29)) at 1 and 4 months postintervention (follow-up 1 and 2). Quality adjusted life years (QALYs) were calculated (EuroQoL 5-Dimensions questionnaire and the Short-form 6-Dimensions questionnaire). RESULTS: Between May 2008 and November 2009, 164 patients were randomised; primary outcome data were available for 146 (89%). Statistically significant differences favour the intervention group on fatigue self-efficacy at follow-up 1 (mean difference (MD) 9, 95% CI (4 to 14), standardised effect size (SES) 0.54, p=0.001) and follow-up 2 (MD 6, 95% CI (0 to 12), SES 0.36, p=0.05) and fatigue severity at follow-up 2 (MD -0.36, 95% CI (-0.63 to -0.08), SES -0.35, p=0.01) but no differences for MSIS-29 or QALYs. No adverse events reported. Estimated cost per person for FACETS is £453; findings suggest an incremental cost-effectiveness ratio of £2157 per additional person with a clinically significant improvement in fatigue. CONCLUSIONS: FACETS is effective in reducing fatigue severity and increasing fatigue self-efficacy. However, it is difficult to assess the additional cost in terms of cost-effectiveness (ie, cost per QALY) as improvements in fatigue are not reflected in the QALY outcomes, with no significant differences between FACETS and CLP. The strengths of this trial are its pragmatic nature and high external validity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76517470.
Asunto(s)
Terapia Cognitivo-Conductual/economía , Terapia Cognitivo-Conductual/métodos , Fatiga/economía , Fatiga/rehabilitación , Estilo de Vida , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/rehabilitación , Esclerosis Múltiple Recurrente-Remitente/economía , Esclerosis Múltiple Recurrente-Remitente/rehabilitación , Psicoterapia de Grupo/economía , Psicoterapia de Grupo/métodos , Adulto , Anciano , Terapia Combinada , Análisis Costo-Beneficio , Evaluación de la Discapacidad , Fatiga/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Autoeficacia , Medicina Estatal/economía , Encuestas y CuestionariosRESUMEN
BACKGROUND: Walking impairment has a major influence on the quality of life of people with multiple sclerosis (MS). The Multiple Sclerosis Walking Scale (MSWS-12) assesses the impact of MS on walking ability from the patient's perspective, but in its current form, is not amenable for use in many policy decision-making settings. OBJECTIVES: Statistical 'mapping' methods were used to convert MSWS-12 scores to EQ-5D health state values. METHODS: The relationship between the measures was estimated using cohort data from people with MS in South West England. Regression analyses were conducted, estimation errors assessed, and predictive performance of the best models tested using longitudinal data. RESULTS: Model performance was in line with that of other mapping studies, with the best-performing models being an ordinary least squares (OLS) model using MSWS-12 item scores, and an OLS model using the total MSWS-12 score and its squared term. CONCLUSIONS: A process has been described whereby data from a patient-reported outcome measure (MSWS-12) can be converted to (EQ-5D) health state values. These values may be used to consider the health-related quality of life of people with MS, to estimate quality adjusted life-years for use in effectiveness and cost-effectiveness analyses, and to inform health policy decisions.
Asunto(s)
Evaluación de la Discapacidad , Política de Salud , Estado de Salud , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Formulación de Políticas , Medicina Estatal/legislación & jurisprudencia , Caminata , Adolescente , Adulto , Anciano , Algoritmos , Análisis Costo-Beneficio , Inglaterra , Femenino , Costos de la Atención en Salud , Política de Salud/economía , Investigación sobre Servicios de Salud , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Crónica Progresiva/psicología , Esclerosis Múltiple Crónica Progresiva/terapia , Esclerosis Múltiple Recurrente-Remitente/economía , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/psicología , Esclerosis Múltiple Recurrente-Remitente/terapia , Valor Predictivo de las Pruebas , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Índice de Severidad de la Enfermedad , Medicina Estatal/economía , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Although the global rate of multiple sclerosis (MS) is low, a few studies have documented high costs. Costs are highly variable depending on MS stage. This study was designed to assess the economic burden of Medicare-eligible patients by MS type in the United States using a claims-based classification algorithm to examine cost variation by disease stage. METHODS: A sample of 2003 to 2006 Medicare patients was selected. Cases were classified as pre-existing progressive MS or pre-existing relapsing-remitting MS (RRMS); the latter were further subdivided into relapsing, remitting, or stable. RESULTS: The sample had 5044 MS subjects, of whom 34.4% had prevalent progressive MS and 65.6% had prevalent RRMS. There were many chronic, comorbid conditions. The mean all-cause Medicare expenditures (not including self-administered medications) per person-year for MS in 2006 were $23,630 for prevalent progressive patients and $5887 for prevalent RRMS patients. Within the RRMS type, Medicare expenditures per person per month in 2006 were $1418 for relapsing patients, $608 for remitting patients, and $331 for stable patients. CONCLUSIONS: There are substantial cost advantages to Medicare for keeping RRMS patients in a stable health state and in keeping them from advancing in disability severity. The overall cost advantage would be diminished by the large cost burden of comorbidity, which would likely remain fixed with improved MS therapies.
Asunto(s)
Costos de la Atención en Salud , Medicare/economía , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Recurrente-Remitente/economía , Adulto , Anciano , Femenino , Gastos en Salud , Estado de Salud , Humanos , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Modelos Econométricos , Análisis Multivariante , Análisis de Regresión , Estados UnidosRESUMEN
Multiple sclerosis (MS) is a chronic disease in which disability progresses over time. Progressive forms of MS have a poor prognosis, are associated with greater levels of disability and, unfortunately, are unresponsive to current treatments. Here, we have reviewed the management of 100 patients with MS. The majority of these patients had progressive disease, Expanded Disability Status Scale scores >6, and extensive medical complications. A significant number of patients in this cohort were also treated with MS disease-modifying agents that lack efficacy in patients with progressive disease. Although these drugs are relatively safe, their use here is significantly costly to the healthcare system, with limited benefit to patients. We suggest that these drugs be discontinued in these patients and resources be directed toward symptomatic treatment, rehabilitation needs, and management of medical complications until drugs with proven efficacy become available.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adulto , Anciano , Evaluación de la Discapacidad , Manejo de la Enfermedad , Femenino , Hospitales de Veteranos , Humanos , Factores Inmunológicos/economía , Inmunosupresores/economía , Interferón beta/economía , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/economía , Ohio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Treatment options for secondary progressive multiple sclerosis (SPMS) are limited. Mitoxantrone is routinely used to stabilize disease progression; however, evolving evidence suggests clinical benefit from intensive treatment with autologous haematopoietic stem cell transplantation (HSCT). Given differences in cost and outcomes, preliminary cost-effectiveness studies are warranted if this approach is to be developed for more widespread application in SPMS. We developed a decision-analytic Markov model to explore the potential cost-effectiveness of autologous HSCT versus mitoxantrone in SPMS, using patient-level data from registry sources. The model evaluates the lifetime costs and health outcomes associated with disability progression and relapse. Sensitivity analyses were undertaken to examine the uncertainty surrounding cost-effectiveness outcomes. In the absence of randomised controlled trial (RCT) evidence, conditions for comparative analysis were not ideal. Under optimistic assumptions, HSCT is estimated to cost below pound3000 per quality adjusted life year gained. However, when a strict 6-month sustained progression rule is adopted, HSCT may be less effective and more expensive than mitoxantrone. The model results were sensitive to reducing procedural costs and HSCT-related mortality. We conclude that HSCT could potentially achieve an acceptable level of cost-effectiveness. However, caution should be exercised as large, high-quality RCTs comparing HSCT versus mitoxantrone are necessary to validate these findings.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/economía , Esclerosis Múltiple Crónica Progresiva/economía , Adolescente , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Mitoxantrona/economía , Mitoxantrona/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/terapia , Años de Vida Ajustados por Calidad de Vida , Sistema de Registros , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development of neurology services to optimize their management.
Asunto(s)
Inmunosupresores/administración & dosificación , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Neurología , Pautas de la Práctica en Medicina , Adulto , Ahorro de Costo , Análisis Costo-Beneficio , Evaluación de la Discapacidad , Esquema de Medicación , Costos de los Medicamentos , Adhesión a Directriz , Humanos , Inmunosupresores/economía , Irlanda/epidemiología , Inutilidad Médica , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Crónica Progresiva/epidemiología , Neurología/economía , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/economía , Servicios de Salud Rural , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Insuficiencia del Tratamiento , Servicios Urbanos de SaludRESUMEN
OBJECTIVE: To evaluate the long-term costs and quality of life (QoL) with and without disease-modifying treatments (DMTs) of patients with multiple sclerosis (MS). METHODS: Data on resource consumption, productivity losses, QoL (utility), and fatigue were collected from 1355 patients registered with a patient association and descriptive analyses was performed.A Markov model was developed to estimate costs and utility over 20 years using the survey data. Disease progression without DMTs was taken from an epidemiological cohort in France (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS registry. Results are presented as cost per quality-adjusted life-years (QALYs), from the societal perspective, in EUR2007, discounted at 3%. RESULTS: Mean Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per patient were EUR44,400, of which 47% were productivity losses and 11% informal care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and the loss compared with the normal population was estimated at 0.28. Costs and utility ranged from EUR16,000 and 0.79 at EDSS 1 to EUR76,000 and 0.11 at EDSS 8-9.Over 20 years, costs were estimated at EUR429,000 and QALYs at 8.96 for patients without DMTs and at EUR433,207 and 9.24 QALYs if all patients were starting treated with DMTs at EDSS 1-3. CONCLUSION: Although the data for this analysis come from different sources, the results indicate that the cost increase with DMTs is moderate.
Asunto(s)
Gastos en Salud/estadística & datos numéricos , Esclerosis Múltiple Crónica Progresiva/economía , Esclerosis Múltiple Recurrente-Remitente/economía , Adolescente , Adulto , Evaluación de la Discapacidad , Fatiga/economía , Fatiga/epidemiología , Fatiga/terapia , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos Econométricos , Esclerosis Múltiple Crónica Progresiva/epidemiología , Esclerosis Múltiple Crónica Progresiva/terapia , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/terapia , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Sistema de Registros/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
The EVIDENCE trial concluded that administering high-dose/high-frequency subcutaneous (SC) interferon-beta-1a (IFNb1a) was more effective in preventing relapses among patients with relapsing multiple sclerosis (MS) than low-dose weekly intramuscular (IM) IFNb1a after 64 weeks. This analysis utilized discrete-event simulation (DES) to model the potential longer-term clinical and economic implications of this trial. A DES predicting the course of relapsing MS and incorporating the effect of IFNb1a therapy was developed. The model began by randomly reading in actual patient data from the trial to create 1000 patients. Each simulated patient was replicated - one was assigned to receive SC IFNb1a three times a week and the other to receive IM IFNb1a once a week. During the simulation, patients may (i) experience relapses, with associated short- and long-term impacts on costs and disability; (ii) develop new T2 lesions detected by a magnetic resonance imaging scan; (iii) discontinue treatment because of adverse events or lack of response; (iv) advance to secondary progressive MS; or (v) die. Model inputs were mainly obtained from the EVIDENCE trial, but were taken from published literature if they could not be obtained from the trial. Direct medical costs ($US, year 2006 values) to the US payers were primarily obtained by updating a published cost analysis. Costs and benefits were discounted at 3% per annum. Extensive sensitivity analyses were conducted to test the robustness of the model results. Based on 100 replications of 1000 patient pairs over 4 years, SC IFNb1a was predicted to enable more patients to avoid relapse (216 vs 147). Total mean costs per patient (discounted) were $US79 890 with SC IFNb1a versus $US74 485 with IM administration, a net increase of $US5405 per patient. However, SC IFNb1a was estimated to prevent 0.50 relapses and save 23 relapse-free days per patient, yielding incremental cost-effectiveness ratios of $US10 755 per relapse prevented and $US232 per relapse-free day gained. Sensitivity analyses revealed that the result was most sensitive to the treatment efficacy, model time horizon and cost of IFNb1a treatment. Based on the results observed in the EVIDENCE trial, the model predicted that SC IFNb1a would yield greater health benefits over 4 years than IM IFNb1a, at a cost that would seem to be a reasonable trade-off.
Asunto(s)
Interferón beta/administración & dosificación , Interferón beta/economía , Modelos Económicos , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/economía , Análisis Costo-Beneficio , Progresión de la Enfermedad , Humanos , Inyecciones Intramusculares , Inyecciones Subcutáneas , Interferón beta-1a , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one or more EDSS points in the prior two years were selected to receive either cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4 years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2 years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS patients were treated for two years with clinical evaluation (relapse rate, disability progression) every three months and radiological imaging (conventional magnetic resonance imaging) before therapy initiation and at the end of the first and second years of therapy. Safety profile and costs of the two therapeutic protocols were also analysed. In terms of clinical and radiological measures the drugs exerted a quite identical effect on both, and produced a significant reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01). Subgroups of mitoxantrone- and cyclophosphamide-responding patients were identified (14/25 and 17/25, respectively) and were characterized by a significantly shorter duration of the secondary progressive phase of the disease. In these subgroups, the improvement in the EDSS score at the end of therapy was highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of both drugs were acceptable; however, the Cy-based therapy protocol was significantly less expensive. We conclude that Cy should be considered as a therapeutic option in rapidly deteriorating SPMS patients.
Asunto(s)
Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Mitoxantrona/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adulto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/economía , Esquema de Medicación , Costos de los Medicamentos , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/economía , Italia , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Mitoxantrona/efectos adversos , Mitoxantrona/economía , Esclerosis Múltiple Crónica Progresiva/economía , Resultado del TratamientoRESUMEN
Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.