Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Developing evidence-based guidelines for the safety of symptomatic drugs in multiple sclerosis during pregnancy and breastfeeding: A systematic review and Delphi consensus.

BACKGROUND: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. OBJECTIVES: This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. METHODS: A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. RESULTS: A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. CONCLUSIONS: Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk-benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.

Anti-CD20 therapies in pregnancy and breast feeding: a review and ABN guidelines.

Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.

Measuring coping in multiple sclerosis: The Coping Index-MS.

BACKGROUND: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores. OBJECTIVE: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement. METHODS: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations. RESULTS: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline. CONCLUSION: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline.

Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.

Psychological determinants of job retention in multiple sclerosis.

BACKGROUND: Maintaining paid work is a key issue for people with multiple sclerosis (PwMS). Different factors, including psychological attributes, can influence job retention. Understanding their role should inform potential interventions to help PwMS retain employment. OBJECTIVES: The aim of this study was to identify the key factors which improve job retention in an employed cohort of PwMS. METHODS: This three-year longitudinal study used validated self-completed measures of physical and psychological factors at four time points over 28 months. RESULTS: Of 208 employed PwMS, just over 1 in 10 was no longer working at the end of the study. Three variables were predictive of continuing employment; low 'work instability' at baseline increased the odds of job retention by a factor of 12.76; high levels of self-efficacy by a factor of 4.66 and being less than 50 years of age increased the odds of job retention by a factor of 3.90. Path analysis demonstrated the mediating role of self-efficacy between the physical impact of MS and the level of work instability at exit. CONCLUSION: Screening for work instability and self-efficacy in a clinical setting followed by appropriate interventions to increase self-efficacy and reduce work instability could aid job retention in MS.

Managing the (In)visibility of Chronic Illness at Work: Dialogism, Parody, and Reported Speech.

Interactionally, the workplace may be dilemmatic for a person with "invisible" chronic illness. Risks of stigmatization exist if they disclose their condition to colleagues. Meanwhile, not disclosing threatens well-being and entitlements. Using Bakhtin's dialogism as a theoretical framework, we explored these social aspects of illness: inductively analyzing narratives from 20 participants with multiple sclerosis (MS). Capitalizing on concepts from dialogical and conversation analysis, links between (in)visibility, knowledge, and belief were examined with respect to symptoms and co-worker judgment. Perceived medical legitimacy creates a core social dilemma. At the intersection of genre and action, participants systematically used parody to subvert the traditional workplace hierarchy. "Oh-prefaced" direct reported speech (OPDRS) was deployed to exaggerate workplace interactions, undermining managers/colleagues who misattributed (in)visible symptoms. Parodic OPDRS index emotive interactional dilemmas. As subversions of organizational power, OPDRS denote those very areas where employees feel disempowered. Sensitivity to OPDRS can provide diagnostic support and complement evaluation frameworks.

Unusual case of bilateral hand weakness.

A 35-year-old man presented with myalgia and bilateral hand weakness, 3 days after the onset of lethargy, fevers and rigours. The hand weakness caused functional impairment including difficulty pressing keys on his mobile phone. On examination, there was mild bilateral hand weakness with normal reflexes. His serum creatine kinase was mildly raised at 503 U/L (24-195), viral PCR throat swab was negative and electromyogram showed subtle myopathic changes in the distal forearm muscles. Nerve conduction studies found no evidence of neuropathy. Forced vital capacity was reduced on admission (1.5 L) but improved within 24 hours (2.3 L). We gave supportive intravenous fluids and his weakness improved within 48 hours. He was discharged and reported that the weakness had fully resolved within weeks. The diagnosis was viral myositis. Distal forearm myositis rarely follows H1N1 influenza in adults but is an important differential for postinfective neurological symptoms.

Myocarditis and diffuse skeletal muscle oedema: new features of neuromyelitis optica spectrum disorder? A case report.

We present a case report of newly diagnosed neuromyelitis optica spectrum disorder (NMOSD) with associated myocarditis and diffuse oedema of the pelvic and anterior compartment thigh muscles on magnetic resonance imaging. Aquaporin 4 antibodies are expressed in skeletal myofibres but involvement of skeletal muscle is rarely reported in NMOSD and myocarditis has not previously been described in this context. This case highlights the need for further research into the involvement of cardiac and skeletal muscle in NMOSD.

A novel tool for characterising upper limb function in progressive multiple sclerosis through kinematic assessment.

INTRODUCTION: Current upper limb assessment methods in MS rely on measuring duration in tasks like the nine-hole peg test (9HPT). Kinematic techniques may provide a more useful measure of functional change in clinical and research practice. The aim of this study was to assess upper limb function prospectively in people with progressive MS using a kinematic 3D motion capture system and compare with current measures. METHODS: 42 people with progressive MS (PwPMS) and 15 healthy controls reached-and-grasped different objects whilst recorded by a kinematic assessment system. 9HPT, Expanded Disability Status Scale (EDSS), and patient reported outcome measures (PROs) were collected. All measures were taken at baseline for PwPMS and controls, and again at six months for PwPMS. RESULTS: Relative to controls, PwPMS had significantly longer reaction (0.11 s, p < 0.05) and reach (0.25 s, p < 0.05) times. PwPMS took longer to pick-up (0.34 s, p < 0.05), move (0.14 s, p < 0.05), and place (0.18 s, p < 0.05) objects. PwPMS had lower peak velocities when reaching (7.4 cm/s, p < 0.05) and moving (7.3 cm/s, p < 0.05) objects. Kinematic assessment demonstrated consistent differences between PwPMS with mild and severe upper limb dysfunction as defined by PROs, which were not captured by 9HPT or EDSS in this group. PwPMS demonstrated altered grip apertures profiles, as measured by their ability to complete individual parts of the reach and grasp task, between the baseline and follow-up timepoints. CONCLUSIONS: We have created and tested a novel upper limb function assessment tool which has detected changes and characteristics in hand function, not currently captured by the EDSS and 9HPT.

Prevalence, treatment and correlates of depression in multiple sclerosis.

BACKGROUND: The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time. METHODS: Participants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression. RESULTS: Baseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2-26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5-29.3), secondary progressive 31.5 % (CI: 29.0-34.0); disability: EDSS 0-4 19.2 % (CI: 17.8-20.6), EDSS ≥4.5 31.9 % (CI: 30.2-33.6); and age: 42-57 years 27.7 % (CI: 26.0-29.3), above or below this range 23.1 % (CI: 21.6-24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6-32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5-28.9). CONCLUSION: A multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence. Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms.

Decision Making About Disease-Modifying Treatments for Relapsing-Remitting Multiple Sclerosis: Stated Preferences and Real-World Choices.

BACKGROUND: People with relapsing-remitting multiple sclerosis can benefit from disease-modifying treatments (DMTs). Several DMTs are available that vary in their efficacy, side-effect profile and mode of administration. OBJECTIVE: We aimed to measure the preferences of people with relapsing-remitting multiple sclerosis for DMTs using a discrete choice experiment and to assess which stated preference attributes correlate with the attributes of the DMTs they take in the real world. METHODS: Discrete choice experiment attributes were developed from literature reviews, interviews and focus groups. In a discrete choice experiment, participants were shown two hypothetical DMTs, then chose whether they preferred one of the DMTs or no treatment. A mixed logit model was estimated from responses and individual-level estimates of participants' preferences conditional on their discrete choice experiment choices calculated. Logit models were estimated with stated preferences predicting current real-world on-treatment status, DMT mode of administration and current DMT. RESULTS: A stated intrinsic preference for taking a DMT was correlated with currently taking a DMT, and stated preferences for mode of administration were correlated with the modes of administration of the DMTs participants were currently taking. Stated preferences for treatment effectiveness and adverse effects were not correlated with real-world behaviour. CONCLUSIONS: There was variation in which discrete choice experiment attributes correlated with participants' real-world DMT choices. This may indicate patient preferences for treatment efficacy/risk are not adequately taken account of in prescribing. Treatment guidelines must ensure they take into consideration patients' preferences and improve communication around treatment efficacy/risk.

MS care: integrating advanced therapies and holistic management.

Lifestyle and environmental factors are key determinants in disease causality and progression in neurological conditions, including multiple sclerosis (MS). Lack of exercise, poor diet, tobacco smoking, excessive alcohol intake, social determinants of health, concomitant medications, poor sleep and comorbidities can exacerbate MS pathological processes by impacting brain health and depleting neurological reserves, resulting in more rapid disease worsening. In addition to using disease-modifying therapies to alter the disease course, therapeutic strategies in MS should aim to preserve as much neurological reserve as possible by promoting the adoption of a "brain-healthy" and "metabolically-healthy" lifestyle. Here, we recommend self-regulated lifestyle modifications that have the potential to improve brain health, directly impact on disease progression and improve outcomes in people with MS. We emphasise the importance of self-management and adopting a multidisciplinary, collaborative and person-centred approach to care that encompasses the healthcare team, family members and community support groups.

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

PURPOSE: Genetic 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 these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK. PARTICIPANTS: Adults with self-reported MS from diverse ancestral backgrounds. Recruitment is via clinical sites, online (https://app.mantal.co.uk/adams) or the UK MS Register. We are collecting demographic and phenotypic data using a baseline questionnaire and subsequent healthcare record linkage. We are collecting DNA from participants using saliva kits (Oragene-600) and genotyping using the Illumina Global Screening Array V.3. FINDINGS TO DATE: As of 3 January 2023, we have recruited 682 participants (n=446 online, n=55 via sites, n=181 via the UK MS Register). Of this initial cohort, 71.2% of participants are female, with a median age of 44.9 years at recruitment. Over 60% of the cohort are non-white British, with 23.5% identifying as Asian or Asian British, 16.2% as Black, African, Caribbean or Black British and 20.9% identifying as having mixed or other backgrounds. The median age at first symptom is 28 years, and median age at diagnosis is 32 years. 76.8% have relapsing-remitting MS, and 13.5% have secondary progressive MS. FUTURE PLANS: Recruitment will continue over the next 10 years. Genotyping and genetic data quality control are ongoing. Within the next 3 years, we aim to perform initial genetic analyses of susceptibility and severity with a view to replicating the findings from European-ancestry studies. In the long term, genetic data will be combined with other datasets to further cross-ancestry genetic discoveries.

Screening for the risk of job loss in multiple sclerosis (MS): development of an MS-specific Work Instability Scale (MS-WIS).

BACKGROUND: Multiple sclerosis (MS) mainly presents amongst those of working age. Depending upon the type of MS, many people embark upon a long period of managing their day-to-day work-related needs in the face of intermittent and sometimes persistent disabling symptoms. The objective of this study was to explore the concept of work instability (WI) following the onset of MS and develop a Work Instability Scale (WIS) specific to this population. METHOD: WI amongst those with MS in work was explored through qualitative interviews which were then used to generate items for a WIS. Rasch analysis was used to refine the scaling properties of the MS-WIS, which was then validated against expert vocational assessment by occupational health physiotherapists and ergonomists. RESULTS: The resulting measure is a 22-item, self-administered scale which can be scored in three bands indicating low, medium and high risk of WI (job retention) problems. The scale meets modern psychometric requirements for measurement, indicated by adequate fit to the Rasch model with absence of local dependency and differential item functioning (DIF) by age, gender and hours worked. CONCLUSIONS: The scale presents an opportunity in routine clinical practice to take positive action to reduce sickness absence and prevent job loss.

Social determinants of health in multiple sclerosis.

Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence health outcomes. Evidence indicates that health behaviours, comorbidities and disease-modifying therapies all contribute to multiple sclerosis (MS) outcomes; however, our knowledge of the effects of social determinants - that is, the 'risks of risks' - on health has not yet changed our approach to MS. Assessing and addressing social determinants of health could fundamentally improve health and health care in MS; this approach has already been successful in improving outcomes in other chronic diseases. In this narrative Review, we identify and discuss the body of evidence supporting an effect of many social determinants of health, including racial background, employment and social support, on MS outcomes. It must be noted that many of the published studies were subject to bias, and screening tools and/or practical interventions that address these social determinants are, for the most part, lacking. The existing work does not fully explore the potential bidirectional and complex relationships between social determinants of health and MS, and the interpretation of findings is complicated by the interactions and intersections among many of the identified determinants. On the basis of the reviewed literature, we consider that, if effective interventions targeting social determinants of health were available, they could have substantial effects on MS outcomes. Therefore, funding for and focused design of studies to evaluate and address social determinants of health are urgently needed.

The contemporary role of MRI in the monitoring and management of people with multiple sclerosis in the UK.

BACKGROUND: Compare the contemporary use of magnetic resonance imaging (MRI) in the monitoring and management of people with MS in the UK to current consensus guidelines. METHODS: This retrospective multicentre audit of clinical practice gathered data on 2567 patients with MS from 25 MS centres across the UK. RESULTS: Routine monitoring (44.7%), and recent clinical relapse (20.3%) were the most common scan indications. In routine monitoring, the addition of spinal imaging to brain showed no significant difference in disease modifying treatment (DMT) decision at subsequent clinical review. Approximately 1 in 5 gadolinium administered scans showed enhancement, and in 1 in 20 patients, gadolinium enhancement was the only evidence of radiological disease activity. Mean inter-scan intervals in relapsing-remitting MS for routine monitoring was 19.2 months (SD 20.7) with wide variation between centres. Only 53.8% of patients under progressive multifocal leukoencephalopathy (PML) surveillance met the recommended scanning frequency. MRI protocols demonstrated heterogeneity in the sequences used for diagnostic, monitoring and PML surveillance scans. CONCLUSIONS: MS centres across the UK demonstrate varied practice and protocols when using MRI to monitor people with MS. In this cohort, gadolinium use and spinal imaging demonstrates limited impact on subsequent DMT decisions.

Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy.

BACKGROUND AND OBJECTIVE: Quality of life in multiple sclerosis (MS) reflects complex relationships between symptoms (fatigue, spasticity pain, and bladder or vision dysfunction), disability, health perceptions, and self-efficacy. METHODS: In this cross-sectional study, a self-report questionnaire pack of patient reported outcome measures was collected from 5695 people with MS (pwMS) alongside clinical data from their neurologists. Each patient reported outcome measure was converted to interval-scaled estimates following fit to the Rasch model. The patient reported outcome measures, as well as perceived health, age, disease subtype and gender, were then subject to path analysis to analyse their relationships with quality of life (QoL), guided by the Wilson and Clearly conceptual framework. RESULTS: The final model explains 81.2% of the variance of QoL. Fatigue is clearly dominant, suggesting a means to intervene and improve QoL. The next most influential factors were disability and self-efficacy, which have similar effect levels. The model can be replicated for pwMS on disease modifying therapy and is largely invariant for gender and disease subtype. Age had an insignificant effect. CONCLUSIONS: In order to promote better QoL, MS care should include management of fatigue, interventions to ameliorate disability, and support to enhance self-efficacy. The range of skills needed for these treatments will require input from medical, nursing, therapy and psychology staff, so these findings provide evidence substantiating the need for pwMS to be provided with care by comprehensive multidisciplinary teams.

OPTIMISE: MS study protocol: a pragmatic, prospective observational study to address the need for, and challenges with, real world pharmacovigilance in multiple sclerosis.

INTRODUCTION: The power of 'real world' data to improve our understanding of the clinical aspects of multiple sclerosis (MS) is starting to be realised. Disease modifying therapy (DMT) use across the UK is driven by national prescribing guidelines. As such, the UK provides an ideal country in which to gather MS outcomes data. A rigorously conducted observational study with a focus on pharmacovigilance has the potential to provide important data to inform clinicians and patients while testing the reliability of estimates from pivotal trials when applied to patients in the UK. METHODS AND ANALYSIS: The primary aim of this study is to characterise the incidence and compare the risk of serious adverse events in people with MS treated with DMTs. The OPTIMISE:MS database enables electronic data capture and secure data transfer. Selected clinical data, clinical histories and patient-reported outcomes are collected in a harmonised fashion across sites at the time of routine clinical visits. The first patient was recruited to the study on 24 May 2019. As of January 2021, 1615 individuals have baseline data recorded; follow-up data are being captured and will be reported in due course. ETHICS AND DISSEMINATION: This study has ethical permission (London City and East; Ref 19/LO/0064). Potential concerns around data storage and sharing are mitigated by the separation of identifiable data from all other clinical data, and limiting access to any identifiable data. The results of this study will be disseminated via publication. Participants provide consent for anonymised data to be shared for further research use, further enhancing the value of the study.

The Impact of Reproductive Issues on Preferences of Women with Relapsing Multiple Sclerosis for Disease-Modifying Treatments.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is an incurable disease characterised by relapses (periods of function loss) followed by full or partial recovery, and potential permanent disability over time. Many disease-modifying treatments (DMTs) exist that help reduce relapses and slow disease progression. Most are contraindicated during conception/pregnancy and some require a discontinuation period before trying to conceive. Although around three-quarters of people with RRMS are women, there is limited knowledge about how reproductive issues impact DMT preference. OBJECTIVE: The aim of this study was to measure the preferences for DMTs of women with RRMS who are considering pregnancy. DESIGN: An online discrete choice experiment (DCE). METHODS: Participants chose between two hypothetical DMTs characterised by a set of attributes, then indicated if they preferred their choice to no treatment. Attributes were identified from interviews and focus groups with people with RRMS and MS professionals, as well as literature reviews, and included the probability of problems with pregnancy, discontinuation of DMTs, and breastfeeding safety. In each DCE task, participants were asked to imagine making decisions in three scenarios: now; when trying to conceive; and when pregnant. ANALYSIS: Two mixed logit models were estimated, one to assess the statistical significance between scenarios and one in maximum acceptable risk space to allow comparison of the magnitudes of parameters between scenarios. SAMPLE: Women with RRMS who were considering having a child in the future, recruited from a UK MS patient register. RESULTS: Sixty respondents completed the survey. Participants preferred no treatment in 12.6% of choices in the 'now' scenario, rising significantly to 37.6% in the 'trying to conceive' scenario and 60.3% in the 'pregnant' scenario (Kruskal-Wallis p < 0.001). This pattern corresponds with results from models that included a no-treatment alternative-specific constant (ASC) capturing differences between taking and not taking a DMT not specified by the attributes. The ASC was lower in the trying to conceive scenario than in the now scenario, and lower still in the pregnant scenario, indicating an intrinsic preference for no treatment. Participants also placed relatively less preference on reducing relapses and avoiding disease progression in the trying to conceive and pregnant scenarios compared with a lower risk of problems with pregnancy. In the trying to conceive scenario, participants' preference for treatments with shorter washout periods increased. CONCLUSION: Women with RRMS considering having a child prefer DMTs with more favourable reproduction-related attributes, even when not trying to conceive. Reproductive issues also influenced preferences for DMT attributes not directly related to pregnancy, with preferences dependent on the life circumstances in which choices were made. The design of the DCE highlights the benefits of considering the scenario in which participants make choices, as they may change over time.