The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.

SummaryBackgroundIn the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.MethodsWe did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348.FindingsBaseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes.InterpretationTo our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials.FundingThe Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University ...

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Introduction Initiating disease-modifying treatments (DMTs) in multiple sclerosis (MS) is a major decision for people with (pw)MS but little is known about how the decision is perceived by the individual. Objectives The aim of the study was to determine if decisional conflict (DC) and decisional regret reflect different stages of the decision-making process when initiating DMTs. Methods This was a cross-sectional study of three cohorts of pwMS ( n = 254), a ‘MS conference attendees’, ‘on treatment’ and an ‘offered treatment’ cohort. Questionnaires assessing DC, decisional regret and control preference were performed. Results Forty-four per cent (113/254) of pwMS were dissatisfied with their treatment status and 53% (135/254) had DC. DC ( p = 0.013) and decisional regret ( p = 0.027) increase in treatment-naïve pwMS and also in those ‘offered treatment’ dissatisfied with their treatment status ( p < 0.0001), whilst those ‘on treatment’ have low Decisional Regret Scale (DRS) score ( p = 0.0005). DC and DRS were only correlated with treatment status in those on treatment and not in treatment-naïve patients. F (58/135) pwMS satisfied with treatment had DC. DC ( n = 236, adjusted R 2 0.137, p = 0.000) and DRS ( n = 235, adjusted R 2 0.232, p = 0.000) were increased by dissatisfaction with treatment, lower potency treatment, being from the ‘MS conference attendees’ cohort and reliance on the doctor’s decision, with DC additionally associated with being employed. Conclusions DC and decisional regret vary in populations at different stages of initiating DMTs and are impacted by non-treatment issues.

Background The role of face-to-face consultations in medicine is increasingly being challenged. Disease activity, national guidelines, life goals e.g. pregnancy, multiple therapies and side effects need to be considered on starting disease modifying treatments (DMTs) in people with multiple sclerosis (pwMS). Objectives We studied the impact of a face-to-face consultation on decision making, using decisional conflict (DC) as the primary outcome. Methods Prospective cohort study of 73 pwMS attending clinics who were making decisions about DMTs followed for one year. Prerequisites and consultation features were measured with the SURE scale for DC used as the primary outcome at baseline and at one year. Results The patient activation measure (PAM) was the only driver prior to the consultation associated with DC (p = 0.02) showing those less engaged were more likely to have DC. Overall, 51/73 (70%) of people made their treatment decision or reinforced a former decision during the consultation. We found making a treatment decision between the original consultation and the follow-up was associated with resolving DC (p = 0.008). Conclusions Patient engagement impacts DC but the HCP delivering the optimal Shared Decision Making (SDM) approach is additionally significant in reducing DC. In complex decisions there is a clear role for face-to-face consultations in current practice.