Comparative Effectiveness and Cost-Effectiveness of Natalizumab and Fingolimod in Patients with Inadequate Response to Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis in the United Kingdom.

BACKGROUND: Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as "BRACETD") often switch to natalizumab or fingolimod. OBJECTIVE: The aim was to estimate the comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD using real-world data and to evaluate the cost-effectiveness of switching to natalizumab versus fingolimod using a United Kingdom (UK) third-party payer perspective. METHODS: Real-world data were obtained from MSBase for patients relapsing on BRACETD in the year before switching to natalizumab or fingolimod or within BRACETD. Three-way-multinomial-propensity-score-matched cohorts were identified, and comparisons between treatment groups were conducted for annualised relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M). Results were applied in a cost-effectiveness model over a lifetime horizon using a published Markov structure with health states based on the Expanded Disability Status Scale. Other model parameters were obtained from the UK MS Survey 2015, published literature, and publicly available UK sources. RESULTS: The MSBase analysis found a significant reduction in ARR (rate ratio [RR] = 0.64; 95% confidence interval [CI] 0.57-0.72; p < 0.001) and an increase in CDI6M (hazard ratio [HR] = 1.67; 95% CI 1.30-2.15; p < 0.001) for switching to natalizumab compared with BRACETD. For switching to fingolimod, the reduction in ARR (RR = 0.91; 95% CI 0.81-1.03; p = 0.133) and increase in CDI6M (HR = 1.30; 95% CI 0.99-1.72; p = 0.058) compared with BRACETD were not significant. Switching to natalizumab was associated with a significant reduction in ARR (RR = 0.70; 95% CI 0.62-0.79; p < 0.001) and an increase in CDI6M (HR = 1.28; 95% CI 1.01-1.62; p = 0.040) compared to switching to fingolimod. No evidence of difference in CDW6M was found between treatment groups. Natalizumab dominated (higher quality-adjusted life-years [QALYs] and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient). Results were consistent across sensitivity analyses. CONCLUSIONS: This novel real-world analysis suggests a clinical benefit for therapy escalation to natalizumab versus fingolimod based on comparative effectiveness results, translating to higher QALYs and lower costs for UK patients inadequately responding to BRACETD.

Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: A combined perspective from the MS in the 21st Century Steering Group.

BACKGROUND: Patient engagement is vital in multiple sclerosis (MS) in order to optimise outcomes for patients, society and healthcare systems. It is essential to involve all stakeholders in potential solutions, working in a multidisciplinary way to ensure that people with MS (PwMS) are included in shared decision-making and disease management. To start this process, a collaborative, open environment between PwMS and healthcare professionals (HCPs) is required so that similarities and disparities in the perception of key areas in patient care and unmet needs can be identified. With this patient-centred approach in mind, in 2016 the MS in the 21st Century Steering Group formed a unique collaboration to include PwMS in the Steering Group to provide a platform for the patient voice. METHODS: The MS in the 21st Century initiative set out to foster engagement through a series of open-forum joint workshops. The aims of these workshops were: to identify similarities and disparities in the perception and prioritisation in three key areas (unmet needs, the treatment burden in MS, and factors that impact patient engagement), and to provide practical advice on how the gaps in perception and understanding in these key areas could be bridged. RESULTS: Combined practical advice and direction are provided here as eight actions: 1. Improve communication to raise the quality of HCP-patient interaction and optimise the limited time available for consultations. 2. Heighten the awareness of 'hidden' disease symptoms and how these can be managed. 3. Improve the dialogue surrounding the benefit versus risk issues of therapies to help patients become fully informed and active participants in their healthcare decisions. 4. Provide accurate, lucid information in an easily accessible format from reliable sources. 5. Encourage HCPs and multidisciplinary teams to acquire and share new knowledge and information among their teams and with PwMS. 6. Foster greater understanding and awareness of challenges faced by PwMS and HCPs in treating MS. 7. Collaborate to develop local education, communication and patient-engagement initiatives. 8. Motivate PwMS to become advocates for self-management in MS care. CONCLUSION: Our study of PwMS and HCPs in the MS in the 21st Century initiative has highlighted eight practical actions. These actions identify how differences and gaps in unmet needs, treatment burden, and patient engagement between PwMS and HCPs can be bridged to improve MS disease management. Of particular interest now are patient-centred educational resources that can be used during time-limited consultations to enhance understanding of disease and improve communication. Actively bridging these gaps in a joint approach enables PwMS to take part in shared decision-making; with improved communication and reliable information, patients can make informed decisions with their HCPs, as part of their own personalised disease management.

Estimate of the cost of multiple sclerosis in Spain by literature review.

INTRODUCTION: Multiple Sclerosis (MS) is a progressive disease leading to increasing disability and costs. A literature review was carried out to identify MS costs and to estimate its economic burden in Spain. Areas Covered: The public electronic databases PubMed, ScienceDirect and IBECS were consulted and a manual review of communications presented at related congresses was carried out. A total of 225 references were obtained, of which 43 were finally included in the study. Expert Commentary: Three major cost groups were identified: direct healthcare costs, direct non-healthcare costs and indirect costs. There is a direct relationship between disease progression and increased costs, mainly direct non-healthcare costs (greater need for informal care) and indirect costs (greater loss of productivity). The total cost associated with MS in Spain is €1,395 million per year, and that the mean annual cost per patient is €30,050. Beyond costs, a large impact on the quality of life of patients, with an annual loss of up to 13,000 quality-adjusted life years was also estimated. MS has a large economic impact on Spanish society and a significant impact on the quality of life of patients.

New insights into the burden and costs of multiple sclerosis in Europe: Results for Spain.

INTRODUCTION: In order to estimate the value of interventions in multiple sclerosis (MS) where lifetime costs and outcomes cannot be observed, outcome data have to be combined with costs. This requires that cost data be regularly updated. OBJECTIVES AND METHODS: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. RESULTS: A total of 462 patients (mean age 43 years) participated in Spain; 96% were below retirement age and of these, 45% were employed. Employment was related to disability, and MS affected productivity at work for 72% of those working. Overall, 92% and 64% of patients experienced fatigue and cognitive difficulties as a problem, respectively. Mean utility and total annual costs were estimated at 0.772 and €20,600 at Expanded Disability Status Scale (EDSS) 0-3, 0.486 and €48,500 at EDSS 4-6.5 and 0.182 and €68,700 at EDSS 7-9, respectively. The mean cost of a relapse was €2050. CONCLUSION: This study illustrates the burden of MS on Spanish patients and provides current data that are important for development of health policies.

[Usefulness of electronic drug registers: Spanish register of patients treated with fingolimod (Gilenya ®)]. / Utilidad de los registros electronicos de medicamentos: registro español de pacientes tratados con fingolimod (Gilenya ®).

INTRODUCTION: This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used. AIMS: To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice. DEVELOPMENT: An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate. CONCLUSIONS: New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it.

TITLE: Utilidad de los registros electronicos de medicamentos: registro español de pacientes tratados con fingolimod (Gilenya ®).Introduccion. Se describe el diseño de un registro electronico de los pacientes con esclerosis multiple que inician tratamiento con fingolimod en España, que se plantea como una herramienta para monitorizar su manejo en la practica clinica habitual que permita optimizar su uso. Objetivos. Conocer el perfil de los pacientes con esclerosis multiple en tratamiento con fingolimod y determinar la efectividad y seguridad de este tratamiento en la practica clinica habitual. Desarrollo. Se establece un registro observacional, retrospectivo y prospectivo, multicentrico, que estara activo durante cinco años. Participaran 40 neurologos de España. Se incluiran pacientes tratados con fingolimod que cumplan los criterios de seleccion. Las variables de efectividad que se evaluaran son: la discapacidad medida mediante la escala ampliada del estado de discapacidad, la tasa de brotes, las lesiones captantes de gadolinio en secuencia T1 y las lesiones nuevas en secuencia T2, y el porcentaje de pacientes libres de actividad y aquellos que requieran tratamientos concomitantes. Las variables de seguridad que se evaluaran son: la tasa de pacientes que presenten acontecimientos y reacciones adversas, respectivamente, analizandose separadamente aquellos que se presenten tras la primera dosis o relacionados con el plan de manejo del riesgo de fingolimod, y la tasa de abandonos del tratamiento. Conclusiones. Los nuevos farmacos de reciente comercializacion requieren mayor informacion acerca de su efectividad y seguridad, mas alla del entorno controlado de un ensayo clinico. Las iniciativas de registros electronicos como el registro Gilenya son la solucion para dar respuesta a dicha necesidad, proporcionando informacion en el menor tiempo posible acerca del manejo mas adecuado para conseguir su uso mas optimo y eficiente posible.