UK Multiple Sclerosis Register Research Articles

The relationship between ethnicity and multiple sclerosis characteristics in the United Kingdom: A UK MS Register study.

Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity. Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures. We used adjusted multivariable linear regression models to explore the association between ethnicity and impact of MS, and Cox proportional hazards models to assess disability progression. We analysed data from 17,314 people with MS, including participants from self-reported Black (n = 157) or South Asian (n = 230) ethnic backgrounds. Age at MS onset and diagnosis was lower in those of South Asian (median 30.0) and Black (median 33.0) ethnicity compared with White ethnicity (median 35.0). In participants with online MS severity measures available, we found no statistically significant evidence for an association between ethnic background and physical disability in MS in both cross-sectional and longitudinal analyses. We found no association between ethnic background and MS severity in a large, diverse UK cohort. These findings suggest that other factors, such as socioeconomic status and structural inequalities, may explain previous findings.

Barriers and strategies to medication adherence amongst people with multiple sclerosis and cognitive problems

BackgroundAdherence to disease-modifying treatment (DMT) amongst people with multiple sclerosis (MS) varies greatly. Although research often identifies 'forgetting' as a reason for poor adherence, few studies have considered how cognitive problems impact adherence. ObjectivesTo investigate prevalence of and barriers to adherence, including for people with MS-related cognitive problems, and to identify adherence-related strategies. MethodsRecruited via the UK MS Register and MS Society groups, participants completed a Medication Adherence Questionnaire and the Perceived Deficits Questionnaire. A subset were interviewed. Results: Of 257 participants, 94 % reported being adherent, although 59 % missed ≥1 dose, and 25 % reported cognitive problems. Adherence was lower amongst those with cognitive problems, who experienced more barriers: memory problems; negative feelings about taking medication; and not wanting medication to interfere with activities. Such barriers, along with mood, cognition, and method of DMT administration, explained 17 % of variance in adherence, with intravenous treatment a significant predictor. Cognitive problems explained a unique proportion of variance; however, was non-significant when anxiety was factored in. Interviews highlighted how anxiety about side-effects and injections, and difficulties accepting the diagnosis, hindered use of reminders. ConclusionInterventions for cognition and mood problems, minimising treatment burden and supporting adjustment to diagnosis, may improve adherence.

University education facilitates uptake of disease-modifying therapies for multiple sclerosis: A community-based study using the UK MS Register.

Higher education is associated with better job opportunities and higher income. Herein, the impact of education on the uptake of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in a publicly funded health care system was examined using the UK MS Register. All adult participants with relapsing remitting MS diagnosed between 2008 and 2021 were included. Those without data regarding their education levels were excluded. Binary, multinomial and Cox regression models were used to examine the association between education levels and uptake of DMTs. A total of 6317 participants fulfilled all inclusion and exclusion criteria. A total of 1826/2923 (62%) participants with a university education were treated with DMTs, compared to 1788/3394 (53%) participants with school/diploma received DMTs with an odds ratio of 1.318 (1.178-1.473). Participants with a university education were more likely to be treated with both moderate- and high-efficacy DMTs, compared to others, with odds ratios of 1.227 (1.087-1.385) and 1.545 (1.325-1.802), respectively. University education was also a positive predictor for faster initiation of DMTs, and, importantly, higher-efficacy DMTs. In a publicly funded health care system, despite intended equality of access, university education was associated with a higher uptake of DMTs.

Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older-Onset Multiple Sclerosis.

Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group? We used data from the UK MS Register to characterize demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years). In the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 28.3, p < 0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease-modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older-onset MS patients. The more progressive nature of older-onset MS is associated with significant neurodegeneration, but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. ANN NEUROL 2024;95:471-486.

Early depressive symptoms and disability accrual in Multiple Sclerosis: a UK MS Register study

Understanding the associations and potential drivers of long-term disability in Multiple Sclerosis (MS) is of clinical and prognostic value. Previous data have suggested a link between depression and disability accrual in MS. We aimed to determine whether depression in early MS predicts subsequent accrual of disability. Using data from the UK MS Register, we identified individuals with and without symptoms of depression and anxiety close to disease onset. We used Cox proportional hazards regression to evaluate whether early depressive or anxiety symptoms predict subsequent physical disability worsening, measured using the Expanded Disability Status Scale (EDSS). We analysed data from 862 people with MS of whom 134 (15.5%) reached an EDSS of ≥ 6.0. Early depressive symptoms were associated with an increased risk of reaching an EDSS of 6.0 (HR 2.42, 95% CI 1.49–3.95, p < 0.001), however this effect dissipated when adjusting for baseline EDSS (HR 1.40, 95% CI 0.84–2.32, p = 0.2). These data suggest that early depressive symptoms in MS are associated with subsequent disability accrual, but are likely the result of disability rather than its cause.

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

PurposeGenetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of...

Using Natural Language Processing to identify patients with Multiple Sclerosis (P3-3.012)

<h3>Objective:</h3> We used text comments from social media sources and the UK MS register (UKMSR) to determine the possibility of identifying MS subjects using natural language processing (NLP). <h3>Background:</h3> Multiple sclerosis (MS) has a wide range of impacts that result in symptoms often being dismissed in the earliest disease phase potentially leading to a delay in diagnosis. Predictive classifiers from natural language processing (NLP) are a potential aid to early identification of symptoms of a range of conditions. These classifiers take as input, patient experience, in text format. Identifying people with MS symptoms earlier could enable them to be directed to the correct resources to confirm a diagnosis. <h3>Design/Methods:</h3> Classifiers were trained using combined social media text data with data from the UKMSR, a database of people clinically diagnosed with MS, where free text entries are collected about their unique experiences. Two control groups were identified: generic social media users and people with self-reported diagnoses of diabetes on social media. Words related to the diagnosis and relevant treatments were removed. We explored three ways to represent text as word vectors and trained seven different machine learning models, including logistic regression, k-nearest neighbors, Naïve Bayes and deep learning approaches. <h3>Results:</h3> 6021 comments from 3037 patients with MS, 6021 comments from 3037 diabetes patients and 6021 comments from 3037 generic social media users were gathered. From the seven models, we achieved a maximum accuracy of 94.3% when classifying experiences of MS patients against generic social media users and a maximum accuracy of 92.4% against diabetes patients. <h3>Conclusions:</h3> The results suggest that NLP-based methods used here can identify people with MS with high accuracy. Further work on more datasets and conditions is required to confirm the utility of these findings but they have the potential to assist accelerating the diagnosis of MS. <b>Disclosure:</b> Mr. Jimulia has received research support from Imperial College London. Dr. Lala has received research support from Imperial College London. Dr. Nicholas has nothing to disclose. The institution of Mr. Middleton has received research support from MS Society.

Multiple sclerosis health-related quality of life utility values from the UK MS register.

New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P). Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics. UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores. The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures. This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.

Psychological flexibility, distress, and quality of life in secondary progressive multiple sclerosis: A cross-sectional study

IntroductionOne of the strongest predictors of successful coping in multiple sclerosis (MS) is the extent to which one can accept the diagnosis and limitations associated with the disease. Acceptance is also one of three core processes of psychological flexibility – a malleable treatment target of some psychological therapies. This is the ability to notice and accept the presence of thoughts and feelings without being swept along by them, engaging in the present moment, and making decisions in line with personal values.Poor psychological flexibility is associated with elevated levels of distress in the general population. However, we do not know the level of psychological flexibility in people with MS, or its relationship to distress or quality of life when the disease becomes more physically disabling. The aims of this study were to determine the level of psychological flexibility, and its relationship with distress and quality of life in secondary progressive multiple sclerosis (SPMS), a subtype of MS with increased severity of disability and distress. MethodThis cross-sectional analytic study used data collected by the UK MS Register. Pre-existing data on distress, quality of life, disability, and demographics collected by the UK MS Register were combined with a psychological flexibility measure and its component parts, collected for the purpose of this study.Patient demographics and questionnaire data were recorded for distress, quality of life, and psychological flexibility. Pearson's correlations were used to examine bivariate relationships between distress, quality of life, disability and psychological flexibility. Whether psychological flexibility moderated the relationship between disability (predictor), distress and quality of life (outcomes) was also investigated. ResultsBetween February and March 2020, 628 participants with SPMS completed the CompACT and had a recent (<12 months) HADS questionnaire (Mage = 60.66, 70.90% women). On the HADS questionnaire subscales, 44% of the sample scored above the MS clinical cut-off (≥8) for anxiety (M = 7.09, SD = 4.57), and 30% above the clinical cut off (≥11) for depression (M = 8.35, SD = 4.21). Psychological flexibility (M = 81.94, SD = 22.60) and its components were each moderately negatively correlated with total distress (r = -0.65), anxiety (r = −0.58), and depression (r = -0.56). A second subsample (n = 434) completed the EQ-5D-5L health-related quality of life measure, which was moderately positively correlated with psychological flexibility (r = 0.47). A third subsample (n = 210) found a weak negative relationship between psychological flexibility and disability (r = -0.16), a weak positive relationship between distress and disability (r = 0.26), and a moderate negative relationship between quality of life and disability (r = -0.56). Psychological flexibility was not found to moderate the relationships between disability and anxiety, depression, or quality of life in SPMS. DiscussionGreater psychological flexibility was associated with lower self-reported distress and higher quality of life in this SPMS sample. It was not shown to moderate the extent to which physical disability predicts distress or quality of life in SPMS.These findings demonstrate that greater psychological flexibility is related to better coping outcomes (lower distress, higher quality of life) in SPMS. If psychological flexibility can be increased in people with SPMS, this could lead to a reduction in distress and improvement in quality of life, although directionality could not be attributed with these methods. Further longitudinal evidence and trials of psychological flexibility-focussed interventions are needed.

A comparison of the measurement properties of the PROMIS Fatigue (MS) 8a against legacy fatigue questionnaires

BackgroundAmidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research was to compare the validity and responsiveness of scores from the PROMIS Fatigue (MS) 8a with those of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), across US and UK MS populations. MethodsTwo observational studies were performed in MS populations as part of a PRO measure development project, including a cross-sectional study in two tertiary US MS centers (n = 340) and a 96-week longitudinal study in the UK MS Register cohort (n = 352). In post-hoc analyses, we examined relative validity, based on ability to discriminate across patient groups with different fatigue levels or functional status at baseline (i.e., ANOVA-F PROX ÷ ANOVA-F PROMIS (MS) 8a), and relative responsiveness, based on baseline-to-Week-52 score change (effect sizes) across fatigue or functional status response groups . ResultsMean ± standard deviation (SD) age was 44.6 ± 11.3/50.0 ± 9.7; and 72.9%/77.3% were female (US/UK samples). The mean PROMIS Fatigue (MS) 8a T-score ± SD at baseline was 57.7 ± 10.5/58.9 ± 9.3 (US/UK samples). Compared with the PROMIS Fatigue (MS) 8a, relative validity (anchor: Global Health Score [GHS] fatigue global question) was 85% for MFIS symptom score, 48% for MFIS total score, and 44% for the FSS. Relative to the FSS, PROMIS Fatigue (MS) 8a scores were more sensitive to worsening (effect size = -0.43 versus -0.18) as well as improvement (effect size = 0.5 versus 0.2) in fatigue (≥1-point increase/decrease in GHS fatigue global question) over 52 weeks of follow-up. A similar pattern of score changes was observed based on a second anchor. ConclusionThe PROMIS Fatigue (MS) 8a scores showed higher responsiveness to fatigue changes than those of the FSS. The PROMIS measure also had higher precision in differentiating levels of fatigue compared to the FSS, the MFIS physical, and MFIS total scores. These differences have practical implications for the application of these questionnaires in both clinical practice and research settings (e.g., sample size estimation in clinical trials).

051 The capture of a UK minimum data set for MS

BackgroundThe UK Multiple Sclerosis Register (UKMSR) was established in 2011 to capture ‘real world’ data from people with MS (pwMS) and the NHS. Capturing clinical data from the NHS for research is time consuming for clinical staff, can involve complicated governance, security and data quality issues. UKMSR has implemented quality controls, validation rules, new capture systems and site reporting to improve this.MethodCompare the Minimum Data Set (MDS) consisting of 7 items including demographics and EDSS for quality and quantity in the first 3 years (pilot phase) to the most recent 3 years of data captureResultsCompletion of MDS (100% valid and completed values) (2011–2014) 4 sites, n=884. MDS received= 159 (17.9%), Time to add site ~3 Months (2017–2020) 48 Sites, n= 8836. MDS received = 5791 (65.5%), Time to add site ~6 WeeksConclusionThe UKMSR has improved the clinical capture of MDS from a vastly increased number of patients and clinical sites. Improved validation standards and systems have increased data quality. Sites are added more quickly and rapidly notified of data quality issues for correction, making the data more useful to the site and ultimately of more utility to researchers.richard.nicholas@btinternet.com

COVID-19 and multiple sclerosis: An updated report of the community-based longitudinal UK MS Register study

COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro- spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start of the COVID-19 outbreak. We report our findings from 17/03/2020 to 15/01/2021.Out of 7344 participants, 883 (12%) have reported a self-diagnosis of COVID-19 of whom 211 had a confirmed clinical or laboratory-based (n=114) diagnosis. No individual DMT increased the likelihood of contracting COVID-19 (with any of the diagnoses as the outcome). Gender (male: female, adjusted OR: 95% CI [0.94: 0.68–1.3]), web-based Expanded Disability Status Scale score (webEDSS; one-point increase, 0.92: 0.84–1.01), and MS duration (one-year increase, 1: 0.98–1.02) were not associated with contracting COVID-19. Younger age (one-year decrease, 1.04: 1.03–1.06), ethnicities other than white (1.95: 1.13–3.34), and relapsing-remitting MS (versus progressive, 1.72: 2.56–1.16) increased the likelihood of contracting COVID-19. Within a median (interquartile range) of 26 (0–72) days follow-up of participants with COVID-19 (n=532), 69% reported full recovery. A higher webEDSS (one-point increase, 0.84: 0.74–0.96) lowered the likelihood of full recovery. Overall, MS-specific factors do not predispose people with MS to contracting COVID-19, but physical disability can delay recovery.afagh.garjani@nottingham.ac.uk

The validity, responsiveness, and score interpretation of the PROMISnq Physical Function – Multiple Sclerosis 15a short form in multiple sclerosis

BackgroundA valid, sensitive patient-reported outcome (PRO) measure of physical function (PF) for people with multiple sclerosis (MS) would have substantial value in routine care and clinical research. We now describe development of the PROMISnq Short Form v2.0 PF – Multiple Sclerosis 15a [PROMISnq PF(MS)15a] for assessing PF in relapsing and progressive MS. Also, the validity, reliability, and responsiveness of the PROMISnq PF(MS)15a is evaluated, minimal important difference (MID) thresholds for score change estimated and a score interpretation guide developed. MethodsA mixed-methods sequential design was employed. Relevant PF concepts were elicited through semi-structured interviews with people with relapsing MS, and then mapped to the PROMIS PF item bank. Measurement experts integrated results from interviews with people with MS and input from a panel of neurologists to generate a draft short form. Relevance and comprehensiveness of the draft short form were assessed in cognitive debriefing interviews with people with relapsing or progressive MS. Subsequently, item reduction and evaluation of psychometric properties were performed in two observational studies: a cross-sectional study in the US (n = 296), and a 96-week longitudinal study in the UK MS Register cohort (n = 558). The main outcomes and measures are estimates of: known-groups validity, convergent validity, reliability, responsiveness; MID for worsening. ResultsFactor analyses supported the unidimensionality of the newly derived 15-item short form. Cronbach's alpha (≥ 0.97) and intraclass correlation coefficient (≥ 0.97) of test-retest scores (5–27 days) indicated strong reliability. Convergent validity was demonstrated by moderate-to-strong correlations with scores on related PRO measures. Scores discriminated among patient groups classified by levels of physical health and other criteria. Score changes of 2.3–2.7 points are proposed as MID criteria for minimal worsening in PF. ConclusionPROMISnq PF(MS)15a demonstrated reliability, validity and sensitivity to change. Input from patients and clinicians ensured the content is comprehensive and relevant for people with MS.

The association between deprivation and the access to disease modifying therapies for multiple sclerosis: An England wide community-based study in the UK MS Register

BackgroundDeprivation can impact the access to health interventions in publicly funded health systems where cost is not the dominant barrier. In this study we examined whether deprivation affected the access to disease modifying therapies (DMTs) for multiple sclerosis (MS). MethodsAll English adults on the UK MS register with relapsing remitting MS who were diagnosed between 2010 and 2017, and after the age of 29 years were included. Deprivation was measured using postcode-based 2015 English index of multiple deprivation (IMD), which was divided into quintiles. ResultsA total of 1449 participants were eligible and 531/1449 (36.6%) received DMTs. Participants who lived in more deprived areas, based on their IMD scores, were significantly less likely to receive DMTs (odds ratio = 0.69, 95% Confidence interval = 0.49 to 0.98); barriers to housing and services contributed to this disparity. The Nagelkerke R2 value of these models showed that 2% of variation in accessing DMTs were dependant on deprivation. ConclusionsDeprivation, as measured by IMD, negatively influences the access to DMTs in England. Our findings also suggest that the lack of access to local MS DMT clinics in deprived areas may contribute to this disparity.

COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register

BackgroundIn March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). ObjectivesExamine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. MethodsAnonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second ‘waves’ of the pandemic. ResultsUnivariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. ConclusionsFeatures associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.

Standardizing fatigue measurement in multiple sclerosis: the validity, responsiveness and score interpretation of the PROMIS SF v1.0 – Fatigue (MS) 8a

BackgroundFatigue is one of the most common and the single most disabling symptom of multiple sclerosis (MS). However, there is a lack of consensus on the most appropriate fatigue measures in clinical practice and research, based upon rigorously validated, generalizable, and publicly available instruments. The objective of this research was to generate additional evidence regarding the validity and applicability of the PROMIS SF v1.0 – Fatigue (MS) 8a, including content validity, reliability, construct validity and responsiveness, as well as to assess minimal important difference (MID) estimates and a score interpretation tool to aide meaningful individual level score interpretation. MethodsA mixed-methods, sequential design was followed. Cognitive debriefing (CD) interviews (n=29) were performed with MS patients, to assess the relevance and comprehensiveness of the PROMIS Fatigue (MS) 8a scores. To evaluate the psychometric properties of the PROMIS Fatigue (MS) 8a, two observational studies were conducted: a cross-sectional study at two US MS centers (n=296), and a 96-week longitudinal study in a UK MS Register cohort (n=384). Main outcomes and measures were estimates of known-groups validity, convergence validity, reliability, and responsiveness, a guide for interpreting PROMIS Fatigue (MS) 8a T-scores, and anchor-based MID estimates. ResultsThe CD interviews confirmed the comprehensiveness and relevance of the PROMIS Fatigue (MS) 8a in assessing MS fatigue. Cronbach's alpha (>0.9) and intra-class correlation coefficient (≥0.9) for test-retest scores at 5–7 days follow-up, supported strong internal consistency and test-retest reliability. Hypothesized differences were found across patient groups in patient reported fatigue and related concepts (analysis of variance [ANOVA], P <0.001). PROMIS Fatigue (MS) 8a scores were sensitive to bi-directional changes in fatigue (GHS fatigue global question) and physical health (PROMIS GHS GPH), over a 52-week follow-up. Score changes of 3.4–4 points are proposed as MID criteria for minimal improvement or worsening in fatigue. ConclusionThis research extends the evidence supporting the content validity and the robust psychometric performance of the PROMIS Fatigue (MS) 8a across US and UK MS populations. Importantly, data supporting the measure's integration in clinical practice and research, including meaningful score interpretation, are now available.

UK Multiple Sclerosis Register: Understanding the Gaps between Patient Experience and Patient Preference within outpatient clinics in the UK. (4642)

UK Multiple Sclerosis Register: Understanding the Gaps between Patient Experience and Patient Preference within outpatient clinics in the UK. (4642)

Exploring the Factors that Influence Workforce Participation for People with Multiple Sclerosis: A Discrete Choice Experiment

Purpose Research indicates that employment is beneficial for people with multiple sclerosis (MS). However, people with MS typically face reduced workforce participation compared to the general population. Using a discrete choice experiment (DCE) we explored which factors are most important in influencing employment choices of people with MS, and whether the relative importance of factors differs between subgroups. Methods Attributes and levels for the DCE were developed using a systematic literature review and public involvement techniques with people with MS. In an online survey, respondents were asked to choose between two hypothetical job scenarios described using six attributes. We used a large, national register (the UK MS Register), to recruit participants aged 18–64 years with a diagnosis of MS. Choice data were analysed using multinomial logit and latent class models. Results Analyses were based on responses from 2350 people with MS. The preferred model specification was a latent class model, with three classes of respondent. The relative importance of attributes varied between classes, with one giving the greatest weight to the impact of work on other aspects of their lives, the second to having supportive bosses and colleagues, and the third to job flexibility. The classes differed significantly in terms of age and gender, type of MS, and socio-economic status. Conclusions Significant heterogeneity was apparent among people with MS regarding the factors that influence their employment decisions. Attributes concerning the impact of work, attitudes in the workplace and job flexibility appear more influential than those concerning physical workplace adaptations.

The Impact of Smoking Cessation on Multiple Sclerosis Disease Progression

OBJECTIVE: To determine the impact of smoking cessation on disease progression in Multiple Sclerosis DESIGN: Retrospective and prospective cohort registry studies. SETTING: UK-wide, community-based. PARTICIPANTS: Adults with confirmed multiple sclerosis (MS) registered on the United Kingdom MS Register. Data was collected between 2011 and 2020. MAIN OUTCOME MEASURE: Retrospective and 4-year prospective parallel group primary outcomes were changes in 3 patient reported outcomes (PROs): normalised MS Physical Impact Scale (MSIS-29-Phys), normalised MS Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS-Anxiety and HADS-Depression). For time to event analysis, primary outcomes were a clinically significant 10-point increase in the MSIS-29-Phys and MSWS-12 score, or a 2-point increase in the HADS-anxiety and HADS-Depression score. RESULTS: 7983 participants were included, 4130 (51.7%) of these had ever smoked; of whom 1315 (16.5%) were still smokers and 2815/4130 (68.2%) were former smokers. For all PROs, still smokers at the time of completing their first questionnaire had higher PRO scores indicating higher disability compared to those who had never smoked (~10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 point for HADS-anxiety and HADS-depression). There was no improvement in PRO scores with increasing time since quitting in former smokers. 922 participants formed the prospective parallel group, which demonstrated that MSIS-29-phy (p<0.0001), MSWS-12 (p=0.0034) and HADS-depression (p=0.007) worsened over a period of 4 years, whereas HADS-anxiety remained stable (p=0.44). Smoking status was significant controlling for time across all PROs (p=0.0023 or less). Post-hoc analysis showed that being a still smoker was associated with a higher score than never smokers for the MSIS-29-Phys (p<0.0001) and MSWS-12 (p<0.0001), whereas former smokers were no different to never smokers. 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all PROs (MSIS-29-Phys: n=4436, p=0.0013; MSWS-12: n=3902, p=0.0061; HADS-anxiety: n=4511, p=0.0017; HADS-depression: n=4511, p<0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-anxiety and HADS-depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. CONCLUSIONS: When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with MS. FUNDING STATEMENT: The UK MS Society, The Berkeley Foundation, The Multiple Sclerosis Trials Collaboration DECLARATION OF INTERESTS:Rodgers, Vonberg, Ford, Middleton, Constantinescu, Emsley, Sharrack, Coles, Duddy, Ford H, McLean, Rog, Husseyin, Hobart, Wilson, Galea, Finisku, McDonnell, Kipps, Straukiene, Marta, Schmierer nothing to disclose Nicholas: Support from advisory boards and travel from Novartis, Roche and Biogen. He has grant support from the UK MS Society and is a member of a NICE HTA committee Friede: personal fees from Bayer, BiosenseWebster, Boehringer Ingelheim, CSL Behring, Daiichi-Sankyo, Fresenius Kabi, Galapagos, Immunic, Janssen, LivaNova, Novartis, Roche, Vifor; all outside the submitted work. Chataway : In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, Novartis and Roche. Harrower : received support to attend meetings, provide advice for adboards, delivering lectures etc from: Merck Serrono, Biogen, UCB, Eisai, Brittania, Ipsen, Allergan, Merz, Revance, GSK, GWP Pharma, Solvay Health Care ETHICS APPROVAL STATEMENT: The UK MS Register has research ethics approval from South West Central Bristol Research Ethics Committee 16/SW/0194.

Fatigue and fluctuations in physical and psychological wellbeing in people with multiple sclerosis: A longitudinal study

BackgroundFatigue is a highly prevalent and disabling symptom of multiple sclerosis (MS). The aetiology remains unclear, potentially resulting from neuroinflammatory or neurodegenerative processes, mood disturbance, MS symptoms including pain, poor sleep, physical decompensation or medication side effects. Cross-sectional associations have been reported between fatigue and markers of physical and psychological health in people with MS. The current study examined if fluctuations in markers of physical and psychological wellbeing were associated with between-person differences in fatigue in MS. MethodsLongitudinal data of up to 7 years was available of 3369 people with MS who were enrolled in the UK MS Register. Participants completed MS impact scale ratings and MS walking scales up to 4 times per year for up to 7 years. Fatigue was assessed at one time point using the Fatigue Severity Scale. Multilevel analyses were conducted to examine the degree of variance in the outcome measures accounted for by fatigue. ResultsFatigue was associated with fluctuations in depression, MS impact, and walking ability, and to a lesser extent with fluctuations in anxiety and perceived health status. Interference of fatigue in participation in social activities and work-related responsibilities and the physical effects of fatigue were most strongly related to MS-related outcomes. ConclusionGiven the strong associations between fatigue and many MS outcomes, fatigue management interventions are likely to impact on different aspects of physical and psychological wellbeing in MS.