Background

Secondary Progressive Multiple Sclerosis (SPMS) is a clinical form of MS characterized by gradual accrual of disability independent of relapses over time. Limited information is available on decision-making in the management of MS. As a consequence, it is frequently diagnosed retrospectively, thus reducing treatment options.

Objectives

To establish consensus on patient monitoring and definition of relevant clinical variables that can support decision making in the early identification and management of disease progression.

Methods

A two-round RAND-UCLA method was used, involving a panel of 15 MS specialists in Spain. A questionnaire consisting of 72 open-ended questions from 3 dimensions (clinical, radiological and biomarkers) was circulated to the experts in Round I. Eleven additional items were included in Round II based on panel feedback in Round I. Items were rated on a 4-point Likert scale and consensus was defined as ≥66% agreement on an item. Final data are presented.

Results

Panellists agreed on the need of monitoring the patients remaining clinically and radiologically stable while on immunomodulators (93%) or immunosuppressors (73%) every 6 months, leaving the special situations to clinical judgement (80% and 93%, respectively). EDSS is the best variable to define progression (93%); six months is the minimum time to confirm disability progression independent of relapses (87%); a worsening of 2-points in any functional system (except the visual), even without changes in EDSS, suggests progression (80%), regardless of disease duration (> 20 years: 93%; 10-20 years: 87%) and age (87%). 20% time increase in T25-FW and 9HPT, together with an increase in EDSS score, are confirmatory of progression (87%). Panellists agreed to perform an annual cognitive exploration (80%), such as SDMT (100%), BRB-N (93%), BICAMS (93%). Experts agreed to evaluate QoL (80%), depression (73%) and fatigue (73%) once annually. A sustained change in brain atrophy suggests progression (80%) provided major physiological factors have been ruled-out (83%). Sustained medullary atrophy suggests progression (100%) but more precise techniques should be used to confirm a diagnosis (93.3%).

Conclusions

The overall consistency in the level of agreement in the different items is high and reinforces the results obtained. These areas of collective agreement could guide neurologists in anticipating progression and planning informed clinical and therapeutic interventions.

Background

Primary progressive multiple sclerosis (PPMS) is a clinical subtype of MS characterized by the progressive accumulation of disability from onset. It is diagnosed in approximately 15% of people with multiple sclerosis (MS).

microRNAs (miRNAs) are small non-coding RNA molecules that participate in the regulation of gene expression. Their role in different diseases, including MS, is being studied.

Current disease-modifying therapies for MS as well as miRNA studies mainly focus on relapsing-remitting MS (RRMS), the most common subtype.

Objectives

The aim of this study was to identify and validate a differential profile of circulating miRNAs in PPMS patients compared to RRMS and controls with other neurological disease (OND) subjects in order to increase our knowledge of the biological processes involved in the different forms of the disease.

Methods

miRNAs were extracted from serum and cerebrospinal fluid (CSF) from a cohort of 111 patients (49 PPMS, 35 RRMS and 27 OND). In the identification phase, samples were analyzed using TaqMan OpenArray Human Advanced MicroRNA panels and in the validation phase, the quantification of the miRNAs was performed by qPCR. Differential expression was analyzed using the Kruskal-Wallis test with the normalized value of miRNAs.

Results

In the identification phase, 10 miRNAs showed differential expression in serum between some of the groups; while in CSF, miR-143-3p presented differential expression in PPMS group (p= 0.009), and let-7b-5p and miR-451a showed a tendency to be deregulated.

In serum samples, the validation phase showed miR-20a-5p overexpression in PPMS compared to controls, and miR-26a-5p among the forms of MS (p= 0.002 and p= 0.036, respectively). On the other hand, miR-142-5p was differentially expressed in RRMS compared to OND (p= 0.036).

In CSF, let-7b-5p and miR-143-3p presented significantly reduced levels in PPMS forms compared to OND (p= 0.029 and p= 0.039, respectively).

Conclusions

miR-20a-5p, miR-26a-5p, let-7b-5p and miR-143-3p present deregulation in PPMS versus RRMS and OND, indicating that they are involved in the pathophysiological mechanisms of PPMS forms. Further studies will be necessary to determine the role of these miRNAs in the development of the different forms of the disease.

Background

Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune, neurodegenerative disease. Around 19% of treated patients with relapsing-remitting MS progress to Secondary Progressive MS (SPMS) 15 years after disease onset, representing the most severe stage of the disease. MS symptoms lead to a general disability, impacting the quality of life of patients and also being related with an important economic burden on the National Health System, the patients, their caregivers and the whole society.

Objectives

There are limited published data on the economic impact of SPMS. The main objective of the study was to estimate the economic impact of SPMS in Spain.

Methods

DISCOVER (CBAF312AES01) is an observational, non-interventional, cross-sectional, retrospective and multicenter study, including 297 SPMS patients ≥18 years treated and monitored according to routine clinical practice in Spain in 34 public hospitals. All data was collected in one single visit. Primary endpoint: total annual cost per patient, including direct healthcare and non-healthcare costs and indirect costs. Interim results from 99 patients are presented.

Results

62.6% females; mean (SD) age 53.1 (9.3) years; 40.4% with higher education; 86.9% living with a relative. Mean (SD) time since first MS diagnosis was 17.5 (8.9) years and since progression to SPMS 5.2 (4.3) years. At diagnosis, mean (SD) EDSS was 2.0 (1.1), being 5.0 (1.1) at the time of progression and 5.9 (0.8) at the study visit, 47.5% patients reaching EDSS>6. 12.8% of patients presented relapses between 12-24 months before the study. According to EQ-5D-5L, mean (SD) utility (<1) was 0.48 (0.27) for patients with Gd+ lesions and/or relapses 2 years before. According to EQ-5D-5L, mean (SD) utility (<1) for patients with cognitive impairment was 0.45 (0.29) vs 0.51 (0.21) for those without it. Mean (SD) utility for Spanish general population was 0.897 (0.21). EDSS score showed a significative effect (P=0.0074) on the economic burden of the disease, with total costs increasing from 14,546€ (EDSS 4-4.5) to 21,918€ (EDSS 5-5.5) and 26,832€ (EDSS=6). Costs related to patients with EDSS=6 from the societal, patient and healthcare system were 6,441€, 8,450€ and 11,941€, respectively.

Conclusions

Interim results of the DISCOVER study revealed a significant economic impact of MS progression, highlighting the importance of implementing therapeutic strategies specific to the SPMS patient within the early stages of progression.

Background

Patients with neuromyelitis optica spectrum disorders (NMOSD) experience a spectrum of symptoms negatively impacting on daily living and quality of life. The systematic assessment of patient perspectives has the capacity to provide crucial clinical information that could otherwise be lost when relying on clinical evaluation alone. However, the patient experience living with NMOSD is limited, in particular implementing standardized patient-reported outcomes (PROs).

Objectives

The primary objective of this study protocol is to assess the health-related quality of life and well-being of NMOSD patients.

Methods

A multicenter, non-interventional, cross-sectional study will be conducted with patients diagnosed with NMOSD (2015 Wingerchuk criteria) (PERSPECTIVES-NMO Study). Primary outcomes measures will be the 29-item Multiple Sclerosis Impact Scale and the Satisfaction with Life Scale. Demographic characteristics, clinical and imaging outcomes will be collected, including the number and type of attacks, antibody status, Expanded Disability Status Scale score, Nine-Hole Peg Test, Timed 25-Foot Walk, and Magnetic Resonance Imaging findings. Cognition will be evaluated using the Rao Brief Repeatable Neuropsychological Battery. Additional outcomes from the patient´s perspective (PROs) will be collected, including symptoms severity (SymptoMScreen questionnaire), fatigue (Fatigue Impact Scale for Daily Use), pain (MOS Pain Effects Scale), mood (Beck Depression Inventory-Fast Screen), perception of stigma (8-item Stigma Scale for Chronic Illness), and work-related difficulties (23-item Multiple Sclerosis Work Difficulties Questionnaire).

Results

Patient recruitment began in December 2019 with a planned total sample of 70 patients. The study is currently ongoing.

Conclusions

The study results are expected to provide meaningful insights into the clinical burden of disease. A better understanding of patient experiences may foster the development of patient-centered specific plans and more targeted rehabilitation in clinical practice.