CSF neurofilament light chain profiling and quantitation in neurological diseases.

Neurofilament light chain is an established marker of neuroaxonal injury that is elevated in CSF and blood across various neurological diseases. It is increasingly used in clinical practice to aid diagnosis and monitor progression and as an outcome measure to assess safety and efficacy of disease-modifying therapies across the clinical translational neuroscience field. Quantitative methods for neurofilament light chain in human biofluids have relied on immunoassays, which have limited capacity to describe the structure of the protein in CSF and how this might vary in different neurodegenerative diseases. In this study, we characterized and quantified neurofilament light chain species in CSF across neurodegenerative and neuroinflammatory diseases and healthy controls using targeted mass spectrometry. We show that the quantitative immunoprecipitation-tandem mass spectrometry method developed in this study strongly correlates to single-molecule array measurements in CSF across the broad spectrum of neurodegenerative diseases and was replicable across mass spectrometry methods and centres. In summary, we have created an accurate and cost-effective assay for measuring a key biomarker in translational neuroscience research and clinical practice, which can be easily multiplexed and translated into clinical laboratories for the screening and monitoring of neurodegenerative disease or acute brain injury.

Guidance for use of neurofilament light chain as a cerebrospinal fluid and blood biomarker in multiple sclerosis management.

Neurofilament light chain (NfL) is a long-awaited blood biomarker that can provide clinically useful information about prognosis and therapeutic efficacy in multiple sclerosis (MS). There is now substantial evidence for this biomarker to be used alongside magnetic resonance imaging (MRI) and clinical measures of disease progression as a decision-making tool for the management of patients with MS. Serum NfL (sNfL) has certain advantages over traditional measures of MS disease progression such as MRI because it is relatively noninvasive, inexpensive, and can be repeated frequently to monitor activity and treatment efficacy. sNfL levels can be monitored regularly in patients with MS to determine change from baseline and predict subclinical disease activity, relapse risk, and the development of gadolinium-enhancing (Gd+) lesions. sNfL does not replace MRI, which provides information related to spatial localisation and lesion stage. Laboratory platforms are starting to be made available for clinical application of sNfL in several countries. Further work is needed to resolve issues around comparisons across testing platforms (absolute values) and normalisation (reference ranges) in order to guide interpretation of the results.

Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury.

OBJECTIVES: Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50-100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status. METHODS: A 45-min immunoassay for serum NfL was developed for use on an automated digital analyzer based on Simoa technology. The analytical performance (sensitivity, precision, reproducibility, linearity, sample type) was characterized and then cross validated across 17 laboratories in 10 countries. Analytical performance for clinical NfL measurement was examined in individual patients with relapsing remitting multiple sclerosis (RRMS) after 3 months of disease modifying treatment (DMT) with fingolimod. RESULTS: The assay exhibited a lower limit of detection (LLoD) of 0.05 ng/L, a lower limit of quantification (LLoQ) of 0.8 ng/L, and between-laboratory imprecision <10 % across 17 validation sites. All tested samples had measurable NfL concentrations well above the LLoQ. In matched pre-post treatment samples, decreases in NfL were observed in 26/29 RRMS patients three months after DMT start, with significant decreases detected in a majority of patients. CONCLUSIONS: The sensitivity characteristics and reproducible performance across laboratories combined with full automation make this assay suitable for clinical use for NfL assessment, monitoring in individual patients, and cross-comparisons of results across multiple sites.

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement.

Cerebrospinal fluid (CSF) analysis is of utmost importance for diagnosis and differential diagnosis of patients with suspected multiple sclerosis (MS). Evidence of intrathecal immunoglobulin G (IgG) synthesis proves the inflammatory nature of the disease, increases diagnostic certainty and substitutes for dissemination in time according to current diagnostic criteria. The gold standard to determine intrathecal IgG synthesis is the detection of CSF-restricted oligoclonal bands (OCBs). However, advances in laboratory methods brought up κ-free light chains (FLCs) as a new biomarker, which are produced in excess over intact immunoglobulins and accumulate in CSF in the case of central nervous system-derived inflammation. Overwhelming evidence showed a high diagnostic accuracy of intrathecal κ-FLC synthesis in MS with sensitivity and specificity of approximately 90% similar to OCB. κ-FLCs have advantages as its detection is fast, easy, cost-effective, reliable, rater-independent and returning quantitative results which might also improve the value of predicting MS disease activity. An international panel of experts in MS and CSF diagnostics developed a consensus of all participants. Six recommendations are given for establishing standard CSF evaluation in patients suspected of having MS. The panel recommended to include intrathecal κ-FLC synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis.

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off. METHODS: PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models. RESULTS: A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1. CONCLUSION: The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.

Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors.

OBJECTIVE: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival. RESULTS: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death-1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow-up magnetic resonance imaging at least once during follow-up (OR = 3.16, 95% confidence interval = 1.20-8.72, p = 0.02) was associated with 1-year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1-month follow-up in survivors compared to nonsurvivors (p < 0.0001). Thirty-two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%). INTERPRETATION: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML-IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257-270.

The relationship of cerebrospinal fluid neurofilament levels with magnetic resonance imaging lesion location and disease activity in multiple sclerosis.

BACKGROUND AND PURPOSE: Neurofilament light chain (NfL) is an accepted biomarker of disease activity in multiple sclerosis (MS), but its relationship with magnetic resonance imaging (MRI) activity particularly in reference to lesion location and recurrent activity is not well understood. METHODS: In 139 MS patients who underwent lumbar punctures with follow-up in 25, the relationship between cerebrospinal fluid (CSF) NfL and cranial MRI based on lesion location and lesion number was evaluated. Spearman rank correlation was used to assess the association between CSF NfL and MRI lesion location and lesion counts at baseline and follow-up at 1 year. Multiple linear regression analysis was performed to assess which lesion location was most strongly associated with CSF NfL values. RESULTS: The associations between baseline CSF NfL and lesion location and follow-up lesions were modest, whilst those between baseline MRI and follow-up CSF NfL were greater: periventricular (r = 0.31, p = 0.141), juxtacortical (r = 0.47, p = 0.022), infratentorial (r = 0.71, p ≤ 0.001) and cord lesions (r = 0.60, p = 0.002). All associations, however, improved following adjustment for disease duration and type of MS. Modelling revealed 53% of (log) CSF NfL could be explained by variance in baseline MRI lesion location. CONCLUSIONS: Baseline CSF NfL did not correlate with current or future MRI activity and lesion location. However, baseline MRI activity explained around 53% of the variation in the follow-up CSF NfL, suggesting that the relationship between MRI and CSF NfL is mainly precedent rather than an association, that is one occurring before the other.

Factors contributing to CSF NfL reduction over time in those starting treatment for multiple sclerosis: An observational study.

BACKGROUND: In multiple sclerosis (MS) neurofilament light chain (NfL) is a marker of neuronal damage secondary to inflammation and neurodegeneration. NfL levels drop after commencement of disease-modifying treatment, especially the highly active ones. However, the factors that influence this drop are unknown. OBJECTIVE: To examine the patient and treatment-related factors that influence CSF NfL before and after starting treatment. METHODS: Eligible patients across two centres with two CSF NfL measurements, clinical and MRI data were included as part of an observational cohort study. RESULTS: Data were available in 61 patients, of which 40 were untreated at the first CSF sampling (T1) and treated at the second (T2; mean T1-T2: 19 months). CSF NfL reduction correlated with age (beta = 1.24 95%CI(1.07,1.43); R2 = 0.17; p = 0.005), Expanded Disability Status Scale (EDSS) (beta = 1.12 95%CI(1.00,1.25); R2 = 0.21; p = 0.05) and the type of MS (beta = 0.63 95%CI(0.43, 0.92); R2 = 0.12; p = 0.018; reference=relapsing MS). The treatment effect on a baseline NfL of 702 pg/mL was 451 pg/ml 95%CI(374,509) in a 30-year-old versus 228 pg/ml 95%CI(63,350) in a 60-year-old. There was no association in CSF NfL reduction with BMI, disease duration or sex. In cladribine- and alemtuzumab-treated patients, the CSF NfL T2/T1 ratio did not correlate with lymphocyte depletion rate at 23 weeks. CONCLUSIONS: In this observational study, we found that factors reflecting early disease stage, including a younger age, lower disability and relapsing MS were associated with treatment response in CSF NfL. Other factors were not found to be related, including lymphopaenia in highly-active treatments.

Antigen-specific tolerization in human autoimmunity: Inhibition of interferon-beta1a anti-drug antibodies in multiple sclerosis: A case report.

BACKGROUND: Antigen-specific tolerance in auto-immune diseases is the goal for effective treatment with minimal side-effects. Whilst this is achievable in animal models, notably via intravenous delivery of the model-specific autoantigen following transient CD4 T cell depletion, specific multiple sclerosis autoantigens remain unproven. However, anti-drug antibodies to human therapeutic proteins represent a model human autoimmune condition, which may be used to examine immune-tolerance induction. Some people with MS (PwMS) on interferon-beta1a (IFNß1a) develop neutralizing antibodies to IFNß1a that do not disappear in repeated tests over years. METHODS: One PwMS was recruited, as part of a planned phase IIa trial (n = 15), who had developed neutralizing antibodies to subcutaneous IFNß1a. Mitoxantrone (12 mg/m2) was administered as a lymphocyte depleting agent followed by four days of (88 µg/day + three 132 µg/day) intravenous IFNß1a. Subcutaneous IFNß1a three times a week was maintained during follow-up. IFNß1a neutralizing antibody responses in serum were measured during treatment and three-monthly for 12 months. FINDINGS: One participant was recruited and, within 6 months of tolerization, the neutralizing antibodies were undetectable. The tolerization treatment was well tolerated. However, the study was terminated after the first enrolment, on ethical grounds, as treatment alternatives became available and the potential risks of mitoxantrone use increased. INTERPRETATION: The data suggest that it may be possible to induce antigen-specific tolerance by providing tolerogenic antigen following transient immune depletion. Further studies are warranted. FUNDING: The study was supported by an unrestricted research grant from Merck-Serono.

Can rheumatologists stop causing demyelinating disease?

BACKGROUND: Perhaps the most informative experiments in human disease are clinical trials and notably, responses to specific therapies can be highly-informative to help understand disease pathogenesis. There are reagents that inhibit a variety of different autoimmune conditions, such as CD20 memory B cell depleters that are active in both multiple sclerosis (MS), rheumatoid arthritis (RA) and other conditions, suggesting influences on common immune mechanisms in different diseases. However, a notable exception seemed to be the use of tumour necrosis factor (TNF) inhibitors that limits RA, yet seem to, rarely, trigger demyelination and induce MS. This was first seen with TNF-inhibiting monoclonal antibodies and TNF-receptor-immunoglobulin fusion proteins. However, this is also seen with tyrosine and Janus kinase inhibitors that inhibit RA, yet induce demyelinating disease in some individuals PURPOSE: To provide an overview, from a B cell centric perspective, that may underpin the biology that links arthritis treatments to the development of demyelinating disease. CONCLUSIONS: It is apparent that the disease modifying anti-rheumatoid drugs that cause demyelination share a number of common features. These agents tend to inhibit TNF-receptor signalling, augment or exhibit limited inhibitor activity on class-switched memory B cells and importantly appear to be relatively excluded from the central nervous system (CNS). They will thus not target ectopic B cell follicles in the CNS, unlike that occurring in peripheral autoimmunity as seen with anti-TNF treatments in RA. Agents such as ibudilast and some Janus kinase inhibitors that inhibit TNF and clearly penetrate the CNS do not appear to induce demyelination and may even be neuroprotective. It remains to be established whether selection or development of CNS penetrant agents may avoid CNS-complications of treatments for RA. Clearly, further studies are warranted.

The Evolution of Neurofilament Light Chain in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune, inflammatory neurodegenerative disease of the central nervous system characterized by demyelination and axonal damage. Diagnosis and prognosis are mainly assessed through clinical examination and neuroimaging. However, more sensitive biomarkers are needed to measure disease activity and guide treatment decisions in MS. Prompt and individualized management can reduce inflammatory activity and delay disease progression. Neurofilament Light chain (NfL), a neuron-specific cytoskeletal protein that is released into the extracellular fluid following axonal injury, has been identified as a biomarker of disease activity in MS. Measurement of NfL levels can capture the extent of neuroaxonal damage, especially in early stages of the disease. A growing body of evidence has shown that NfL in cerebrospinal fluid (CSF) and serum can be used as reliable indicators of prognosis and treatment response. More recently, NfL has been shown to facilitate individualized treatment decisions for individuals with MS. In this review, we discuss the characteristics that make NfL a highly informative biomarker and depict the available technologies used for its measurement. We further discuss the growing role of serum and CSF NfL in MS research and clinical settings. Finally, we address some of the current topics of debate regarding the use of NfL in clinical practice and examine the possible directions that this biomarker may take in the future.

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients.

OBJECTIVE: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. METHODS: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. RESULTS: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. CONCLUSIONS: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

Serum neurofilament-light concentration and real-world outcome in MS.

BACKGROUND: Prognostication in multiple sclerosis (MS) remains challenging. Biomarkers capable of providing this information at diagnosis would be valuable in shaping therapeutic decisions. Measurement of neurofilament light (NfL) has shown promise in predicting clinical outcomes in established MS, but its ability to predict outcomes in real-world cohorts at diagnosis requires further validation. METHODS: We used linear regression to evaluate the relationship between serum NfL (sNfL), measured at the time of diagnosis with short-term (1-year) and medium-term (5-year) clinical outcomes in 164 people with MS from a real-world, population-based cohort. Cox proportional hazards regression was used to analyse the association between sNfL and subsequent hazard of relapse or sustained accumulation of disability (SAD). Analyses were adjusted for age and disease-modifying treatment (DMT). RESULTS: sNfL concentration at diagnosis was modestly associated with baseline EDSS score (ß = 0.272, 95% CI 0.051 to 0.494, p = 0.016). However, no significant associations were found between baseline sNfL and odds of relapse at 12-months, 5-year EDSS change, or the hazard of relapse or SAD over 5 years follow-up. Dichotomising baseline sNfL according to the median sNfL did not change these findings. CONCLUSIONS: sNfL appears to be of limited clinical utility in predicting future irreversible neurological disability in a largely untreated real-world population, and remains insufficiently validated to shape treatment decisions at the time of diagnosis. Further studies may be needed for sNfL to be considered as a prognostic marker in the MS clinic. However the masking effect of DMTs on the natural disease trajectory will continue to pose challenges.

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS.

OBJECTIVE: To evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS. METHODS: This was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as "No Treatment/No Escalation" (no treatment or no escalation of treatment) or "Treatment/Escalation" (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up. RESULTS: Of 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81). CONCLUSIONS: CSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

Protecting people with multiple sclerosis through vaccination.

Vaccination is one of the most effective and cost-efficient methods for protecting people with multiple sclerosis (MS) from infections. However, use of vaccines has often been problematic because of misguided concerns that they may exacerbate the disease and/or that some disease-modifying therapies may influence the immune response to immunisations and/or their safety. People with MS risk higher morbidity and mortality from vaccine-preventable infections. It is, therefore, important to address any patient's reluctance to accept vaccination and to provide clear guidance for clinicians on which vaccinations to consider proactively. We have reviewed the current literature and provide recommendations regarding vaccines in adults with MS, including specific advice regarding vaccination safety in patients receiving-or going to receive-disease-modifying therapies, vaccination during pregnancy, pretravel counselling and patient education.

Socioeconomic status and disease-modifying therapy prescribing patterns in people with multiple sclerosis.

AIMS: To examine the association between socioeconomic status (SES) and disease-modifying therapy (DMT) prescribing patterns in people with relapsing-remitting multiple sclerosis (pwRRMS). METHODS: A cross-sectional analysis was conducted among pwRRMS treated with a DMT in the neuroinflammation service at The Royal London Hospital (Barts Health NHS Trust). Study data were collected between July and September 2017. SES was determined by patient income and education extracted from the English Index of Multiple Deprivation. Based on their efficacy, DMTs were categorized as moderate efficacy (Glatiramer Acetate and Beta-Interferons), high efficacy (Cladribine, Fingolimod and Dimethyl Fumarate) and very-high efficacy therapies (Natalizumab and Alemtuzumab). Multinomial logistic regressions were performed for univariate and multivariate models to assess differences between SES and DMT prescribing patterns. RESULTS: Treatment consisted of moderate efficacy (n = 76, 12%), high efficacy (n = 325, 51.3%) and very-high efficacy therapies (n = 232, 36.7%). Medians for income and education deciles were 4 (IQR 3-7) and 6 (IQR 4-8), respectively. After multinomial logistic regression analysis, patient income was not associated with increased odds of being treated with high efficacy (OR, 0.92; 95% CI, 0.82-1.04; p = 0.177) or very-high efficacy DMTs (OR, 0.95; 95% CI, 0.85-1.06; p = 0.371). Similarly, patient education was not associated with being treated with high efficacy (OR, 0.91; 95% CI, 0.80-1.03; p = 0.139) or very-high efficacy therapies (OR, 0.92; 95% CI, 0.81-1.04; p = 0.188). CONCLUSIONS: SES was not predictive of DMT prescribing patterns in pwRRMS. Whilst this appears reassuring within this universal health care setting, the same methodology needs to be applied to other MS services for comparison. Data could then be further interrogated to explore potential socioeconomic inequities in DMT prescribing patterns across the UK.