No Evidence Of Disease Activity Research Articles

DNA Methylation in the Anti-Mullerian Hormone Gene and the Risk of Disease Activity in Multiple Sclerosis.

Multiple sclerosis (MS) has a complex pathobiology, with genetic and environmental factors being crucial players. Understanding the mechanisms underlying heterogeneity in disease activity is crucial for tailored treatment. We explored the impact of DNA methylation, a key mechanism in the genetics-environment interplay, on disease activity in MS. Peripheral immune methylome profiling using Illumina Infinium MethylationEPIC BeadChips was conducted on 249 untreated relapsing-remitting MS patients, sampled at the start of disease-modifying treatment (DMT). A differential methylation analysis compared patients with evidence of disease activity (EDA) to those with no evidence of disease activity (NEDA) over 2 years from DMT start. Utilizing causal inference testing (CIT) and Mendelian randomization (MR), we sought to elucidate the relationships between DNA methylation, gene expression, genetic variation, and disease activity. Four differentially methylated regions (DMRs) were identified between EDA and NEDA. Examining the influence of single nucleotide polymorphisms (SNPs), 923 variants were found to account for the observed differences in the 4 DMRs. Importantly, 3 out of the 923 SNPs, affecting DNA methylation in a DMR linked to the anti-Mullerian hormone (AMH) gene, were associated with disease activity risk in an independent cohort of 1,408 MS patients. CIT and MR demonstrated that DNA methylation in AMH acts as a mediator for the genetic risk of disease activity. This study uncovered a novel molecular pathway implicating the interaction between DNA methylation and genetic variation in the risk of disease activity in MS, emphasizing the role of sex hormones, particularly the AMH, in MS pathobiology. ANN NEUROL 2024.

Long-term follow up of alemtuzumab-treated patients: a retrospective study in a Belgian tertiary care center.

Pivotal studies have reported a significant proportion of patients achieving no evidence of disease activity (NEDA) after 2 cycles of treatment with alemtuzumab (ATZ), that can be maintained for several years. Long-term real-world evidence regarding ATZ as well as subsequent treatment trajectories is still scarce. To analyze the effectiveness and safety of ATZ-treated patients in a tertiary care Belgian center. A retrospective cohort study including 32 patients treated with ATZ between 2015 and 2021 was performed. 32 patients received 2 ATZ courses with a mean follow-up (FU) duration of 5.6years (range: 2.25-8.2). 21.75% patients were treatment naïve. 40.5% were previously treated with natalizumab or fingolimod. NEDA-3 was achieved in 61.3-85% of patients, with failure mostly attributed to recurrence of radiological disease activity. During FU, annualized relapse rates remained very low (0.06-0.14), disability improvement occurred in up to 40.5%, whereas disability worsening occurred in up to 13.5%. Retreatment risk was associated with younger age (< 45years old, Odds Ratio 8.0, p = 0.02) and a higher number of previous DMTs (Hazard ratio 2.7, 95%CI 1.3-7.4, p = 0.02). Safety in our cohort was consistent with the known profile of ATZ. At the end of FU, 65.6% patients remained untreated after 2 or 3 courses of ATZ, while the remaining switched to anti-CD20 therapy or cladribine. ATZ is a high efficacy therapy for active MS, providing long-term remission in a significant proportion of patients. Retreatment was more frequent in younger patients or patients having failed a higher number of previous DMTs.

High frequency of circulating non-classical monocytes is associated with stable remission in relapsing-remitting multiple sclerosis

‘No evidence of disease activity (NEDA)’, judged by clinical and radiological findings, is a therapeutic goal in patients with multiple sclerosis (MS). It is, however, unclear if distinct biological mechanisms contribute to the maintenance of NEDA. To clarify the immunological background of long-term disease stability defined by NEDA, circulating immune cell subsets in patients with relapsing-remitting MS (RRMS) were analyzed using flow cytometry. Patients showing long-term NEDA (n = 31) had significantly higher frequencies of non-classical monocytes (NCMs) (6.1% vs 1.4%) and activated regulatory T cells (Tregs; 2.1% vs 1.6%) than those with evidence of disease activity (n = 8). The NCM frequency and NCMs to classical monocytes ratio (NCM/CM) positively correlated with activated Treg frequency and duration of NEDA. Co-culture assays demonstrated that NCMs could increase the frequency of activated Tregs and the expression of PD-L1, contributing to development of Tregs, was particularly high in NCMs from patients with NEDA. Collectively, NCMs contribute to stable remission in patients with RRMS, possibly by increasing activated Treg frequency. In addition, the NCM frequency and NCM/CM ratio had high predictive values for disease stability (AUC = 0.97 and 0.94, respectively), suggesting these markers are potential predictors of a long-term NEDA status in RRMS.

The first study of real-world efficacy and safety of Natalizumab (Tysabri®) in Iran

Objectives: Natalizumab is an injectable DMT (disease-modifying therapy) which used for RRMS (relapsing-remitting multiple sclerosis) since 2006. The drug has been available in Iran since 2014. Introduction: This study was aimed to evaluate the real-world effectiveness of Natalizumab in a referral center in Tehran, Iran. This study is the first real world analysis of efficacy and safety of Natalizumab in our country. Methods: In this retrospective study, patients with RRMS were investigated in a high-volume center in Tehran from 2019 to 2021. MS (Multiple Sclerosis) patients under treatment with Natalizumab who have received at least 3 infusions of the drug and had completed follow-up data, have been evaluated for safety and efficacy of Natalizumab. Results: 100 patients were included in the final analysis. The mean follow-up time was 20 months (6–33 months). The median EDSS (Expanded Disability Status Scale) score of patients reached to 2 from 2.5 after the treatment course (P &lt; 0.0001). The annualized relapse rate (ARR) decreased from 0.81 (95% CI: 0.73–0.87) to 0.023 (95% CI 0.009–0.061). The median JCV (John Cunningham virus) index remained unchanged before treatment 0.85 (IQR: 0.21–2.41) compare to after the treatment 0.85 (IQR: 0.21–2.31). The number of patients with active brain and cervical MRI (Magnetic Resonance Imaging) lesions decreased significantly (P = 0.001). NEDA-3 (No evidence of disease activity) was improved from 9% to 87% after the treatment with Natalizumab. No serious adverse events except than one progressive multifocal encephalopathy (PML) case have been found. The main reasons of switching from Natalizumab to the other DMDs (Disease Modifying Drugs) were positive JC index, starting phase, noncompliance, pregnancy, MRI activity and seroconversion after starting the drug. Conclusion: Natalizumab is a safe and effective choice in RRMS patients for reducing relapse rate, disability score, active MRI lesion, and improving the NEDA (No evidence of disease activity).

Predicting disease severity in multiple sclerosis using multimodal data and machine learning.

Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre. We found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts. Combining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.

Prevalence of 2-year "No evidence of disease activity" (NEDA-3 and NEDA-4) in relapsing-remitting multiple sclerosis. A real-world study.

No evidence of disease activity (NEDA) is becoming a gold standard in the evaluation of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS). NEDA-3 status is the absence of relapses, new activity on brain MRI, and disability progression. NEDA-4 meets all NEDA-3 criteria plus lack of brain atrophy. Aim of this study was to investigate the prevalence of two-year NEDA-3, NEDA-4, six-month delayed NEDA-3 (6mdNEDA-3), and six-month delayed NEDA-4 (6mdNEDA-4) in a cohort of patients with RRMS. Six-month delayed measures were introduced to consider latency of action of drugs. Observational retrospective monocentric study. All the patients with RRMS starting DMT between 2015 and 2018, and with 2-year of follow-up, were included. Annualized brain volume loss (a-BVL) was calculated by SIENA software. We included 108 patients, the majority treated with first line DMT. At 2-year follow-up, 35% of patients were NEDA-3 (50% 6mdNEDA-3), and 17% NEDA-4 (28% 6mdNEDA-4). Loss of NEDA-3 status was mainly driven by MRI activity (70%), followed by relapses (56%), and only minimally by disability progression (7%). In our cohort 2-year NEDA status, especially including lack of brain atrophy, was hard to achieve. Further studies are needed to establish the prognostic value of NEDA-3 and NEDA4 in the long-term follow-up.

Stem Cell Transplantation for Multiple Sclerosis: A 2023 Review of Published Studies.

This comprehensive literature review underscores the potential of stem cell transplantation (SCT) as a therapeutic intervention for multiple sclerosis (MS). By amalgamating evidence from various sources, including randomized controlled trials (RCTs), observational, retrospective, and comparative studies, this review offers a holistic understanding of SCT's effectiveness, safety, and feasibility in diverse contexts of MS management. SCT has shown promise in mitigating disease activity and progression, particularly in relapsing-remitting MS (RRMS). RCTs like the high dose immunoablation and autologous hematopoietic stem cell transplantation in MS (ASTIMS) versus mitoxantrone therapy in severe multiple sclerosis and multiple sclerosis international stem cell transplant (MIST) trials reveal SCT's capacity to reduce new lesion occurrences and inflammatory activity. However, variability exists in disability score improvements among these studies. Observational and retrospective investigations further affirm SCT's potential, highlighting decreased relapse rates, enhanced expanded disability status scale (EDSS) scores, and a noteworthy proportion of patients achieving no evidence of disease activity (NEDA). The initial literature search using all of the search items produced a total of 3,636 articles. After title, abstract, and article type screening and article retrieving, 147 articles were assessed for eligibility using the inclusion criteria. At the end of the literature search, 37 articles met the eligibility criteria. They were included in our review according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Patients treated with hematopoietic stem cell transplantation (HSCT) present lower progression and relapse rates, suppression of inflammatory activity, and a greater reduction in T2 lesions on MRI than those treated with disease-modifying therapies (DMTs). In summary, while SCT presents promise as a therapeutic option for MS, its deployment should be tailored to individual patient characteristics, disease stages, and responses.

A real-world clinical validation for AI-based MRI monitoring in multiple sclerosis

Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequate clinical validation. In 397 multi-center MRI scan pairs acquired in routine practice, we demonstrate superior case-level sensitivity of a clinically integrated AI-based tool over standard radiology reports (93.3% vs 58.3%), relative to a consensus ground truth, with minimal loss of specificity. We also demonstrate equivalence of the AI-tool with a core clinical trial imaging lab for lesion activity and quantitative brain volumetric measures, including percentage brain volume loss (PBVC), an accepted biomarker of neurodegeneration in MS (mean PBVC −0.32% vs −0.36%, respectively), whereas even severe atrophy (>0.8% loss) was not appreciated in radiology reports. Finally, the AI-tool additionally embeds a clinically meaningful, experiential comparator that returns a relevant MS patient centile for lesion burden, revealing, in our cohort, inconsistencies in qualitative descriptors used in radiology reports. AI-based image quantitation enhances the accuracy of, and value-adds to, qualitative radiology reporting. Scaled deployment of these tools will open a path to precision management for patients with MS.

No Evidence of Disease Activity (NEDA) as a Clinical Assessment Tool for Multiple Sclerosis: Clinician and Patient Perspectives [Narrative Review].

The emergence of high-efficacy therapies for multiple sclerosis (MS), which target inflammation more effectively than traditional disease-modifying therapies, has led to a shift in MS management towards achieving the outcome assessment known as no evidence of disease activity (NEDA). The most common NEDA definition, termed NEDA-3, is a composite of three related measures of disease activity: no clinical relapses, no disability progression, and no radiological activity. NEDA has been frequently used as a composite endpoint in clinical trials, but there is growing interest in its use as an assessment tool to help patients and healthcare professionals navigate treatment decisions in the clinic. Raising awareness about NEDA may therefore help patients and clinicians make more informed decisions around MS management and improve overall MS care. This review aims to explore the potential utility of NEDA as a clinical decision-making tool and treatment target by summarizing the literature on its current use in the context of the expanding treatment landscape. We identify current challenges to the use of NEDA in clinical practice and detail the proposed amendments, such as the inclusion of alternative outcomes and biomarkers, to broaden the clinical information captured by NEDA. These themes are further illustrated with the real-life perspectives and experiences of our two patient authors with MS. This review is intended to be an educational resource to support discussions between clinicians and patients on this evolving approach to MS-specialized care.

Dairy and gluten in disease activity in multiple sclerosis.

Many diets promoted specifically for multiple sclerosis have been suggested to improve disease activity. Dairy and gluten are two components for which the recommendations vary between these diets. Existing research into the association between these dietary components and disease activity has been conflicting. To explore the relationship between dairy and gluten intake and disease activity in multiple sclerosis over a 2-year period, using no evidence of disease activity (NEDA) 3 status. 186 participants' dairy and gluten intake was retrospectively estimated over 2 years using a dairy and gluten dietary screener. Estimated dairy and gluten intake was compared to disease activity, indicated by no evidence of disease activity 3 status, and quality of life, assessed by the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire. No significant association was found between mean estimated dairy or gluten intake and NEDA 3 status (p = 0.15 and 0.60, respectively). Furthermore, there was no significant relationship between dairy or gluten intake and MusiQoL) scores (p = 0.11 and 0.51, respectively). Whilst we cannot rule out modest benefits due to our small sample size, we found that neither dairy nor gluten intake was associated with disease activity or quality of life in this study.

Assessing 'no evidence of disease activity' status in patients with relapsing-remitting multiple sclerosis: a long-term follow-up.

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS with an autoimmune pathogenesis. Over the years, numerous disease-modifying therapies (DMTs) have proven effective in disease control; to date, there is a need to identify a personalized treatment effective in ensuring disease-free status or no evidence of disease activity (NEDA). identify clinical, demographic and treatment approach characteristics that affect the maintenance of NEDA-3 and the occurrence of clinical relapses during a 6-years follow-up. a retrospective study was conducted on a cohort of MS patients followed up with six-year period. All participants were treated with first- or second-line MS drugs.Clinical relapse, NEDA-3 at 6 years and sustained EDSS were assessed as disease activity outcomes. Patients with follow-up of less than 6 years and insufficient clinical and radiological data were excluded from the study. Two-hundred-eighty naive patients (mean age was 49.8 years, SD ± 11.35 years, 23-76, F/M 182/98), with MS were followed up for 6 years.The mean age at diagnosis was 34.3 years (SD ±11.5, 14-62 years), the mean EDSS score at the onset was 1.9 (±1.3), 76.8% of patients had an EDSS below or equal to 2.5 at diagnosis.In the cohort 37 (13.2%) directly received second-line treatment, 243 (86.8%) received first-line drugs.The analysis showed that second-line treatment from beginning had a protective effect for the achievement of NEDA-3 (p = 0.029), on the prevention of clinical relapse (p = 0.018) and on number of relapses (p = 0.010); this finding was confirmed by logistic regression analysis (p = 0.04) and Kaplan-Meier analysis (p = 0.034). The results of this study demonstrate the efficacy of targeted and early intervention so as to act in the right time window, ensuring a favorable outcome in both clinical and radiological terms; this could be decisive in reducing clinical relapse, disease progression and related disability. Therefore, prescribing highly effective drug in the early stages of the disease represents a leading strategy with the most favorable cost-benefit ratio.

Annual Plasma Neurofilament Dynamics Is a Sensitive Biomarker of Disease Activity in Patients with Multiple Sclerosis.

Background and Objectives: Neurofilament light chain (NfL) is a sensitive biomarker of neuroaxonal damage. This study aimed to assess the relationship between the annual change in plasma NfL (pNfL) and disease activity in the past year, as defined by the concept no evidence of disease activity (NEDA) in a cohort of multiple sclerosis (MS) patients. Materials and Methods: Levels of pNfL (SIMOA) were examined in 141 MS patients and analyzed in relationship to the NEDA-3 status (absence of relapse, disability worsening, and MRI activity) and NEDA-4 (NEDA-3 extended by brain volume loss ≤ 0.4%) during the last 12 months. Patients were divided into two groups: annual pNfL change with an increase of less than 10% (group 1), and pNfL increases of more than 10% (group 2). Results: The mean age of the study participants (n = 141, 61% females) was 42.33 years (SD, 10.17), and the median disability score was 4.0 (3.5-5.0). The ROC analysis showed that a pNfL annual change ≥ 10% correlates with the absence of the NEDA-3 status (p < 0.001; AUC: 0.92), and the absence of the NEDA-4 status (p < 0.001; AUC: 0.839). Conclusions: Annual plasma NfL increases of more than 10% appear to be a useful tool for assessing disease activity in treated MS patients.

Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 after Re-baselining in the Phase 3 EVOLVE-MS-1 Study (P8-3.001)

<h3>Objective:</h3> To assess No Evidence of Disease Activity (NEDA) in patients on diroximel fumarate (DRF). <h3>Background:</h3> NEDA, a composite endpoint of clinical and MRI outcomes, is increasingly evaluated in multiple sclerosis (MS) studies. However, carry-over disease activity, before achieving the full effect of a disease-modifying therapy, may confound NEDA outcomes. Previous analyses with DRF and dimethyl fumarate (DMF), oral fumarates for relapsing MS, showed significant reductions in MRI activity as early as 7 weeks after initiation. <h3>Design/Methods:</h3> Patients with relapsing-remitting MS (aged 18–65 years) completing EVOLVE-MS-2 (NCT03093324), a randomized, blinded, 5-week, phase 3 study of DRF or DMF could continue into EVOLVE-MS-1 (NCT02634307), an open-label, 96-week study assessing DRF safety, tolerability, and efficacy. Relapses, Expanded Disability Status Scale scores, and MRI parameters were assessed during screening or on Day 1 of each study (~7 weeks apart). In this analysis, patients who had received DRF in both studies were re-baselined after ~7 weeks’ DRF treatment, and NEDA-3 was assessed over 96 weeks. <h3>Results:</h3> Overall, 239 patients received DRF in EVOLVE-MS-2 and entered EVOLVE-MS-1. Mean (standard deviation) age was 44.0 (11.0) years; 69.0% (n=165) were female. Over 96 weeks, the estimated proportion of patients who achieved NEDA-3 was 50.2%. Most patients (84.1%) were relapse-free on DRF over 96 weeks. An estimated 92.4% of patients were free of 24-week confirmed disability progression; 90.2% had no gadolinium-enhancing lesions; and 79.2% were free of new/newly-enlarging T2 lesions during the full study. Treatment-emergent adverse events occurred in 212 (88.7%) patients; 23 (9.6%) patients discontinued DRF due to adverse events. <h3>Conclusions:</h3> At Week 96, 50.2% of patients on DRF achieved NEDA-3 after re-baselining. Safety outcomes were consistent with those previously reported for EVOLVE-MS-1; discontinuations due to adverse events were low. Re-baselining may be useful for assessing DRF efficacy by mitigating the influence of disease activity prior to the onset of efficacy. <b>Disclosure:</b> Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen IDEC. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for BristolMyers Squibb. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bowen has received research support from Biogen IDEC. The institution of Dr. Bowen has received research support from Genentech. The institution of Dr. Bowen has received research support from Genzyme. The institution of Dr. Bowen has received research support from Novartis. The institution of Dr. Bowen has received research support from Roche. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD serono . Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD serono . Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi . The institution of Dr. Stulc has received research support from EMD serono . The institution of Dr. Stulc has received research support from Novartis . The institution of Dr. Stulc has received research support from Sanofi . The institution of Dr. Stulc has received research support from Genentech. The institution of Dr. Stulc has received research support from Biogen. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbview. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMDSerono. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Osmotica. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMDSerono. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Hunter has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Hunter has received research support from Biogen. The institution of Dr. Hunter has received research support from Abbvie. The institution of Dr. Hunter has received research support from Genentech/Roche. The institution of Dr. Hunter has received research support from Janssen. The institution of Dr. Hunter has received research support from Novartis. The institution of Dr. Hunter has received research support from Osmotica. The institution of Dr. Hunter has received research support from Sanofi. Dr. Hunter has received intellectual property interests from a discovery or technology relating to health care. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with MS Views and News. Dr. Hunter has a non-compensated relationship as a CEO - Volunteer with NeuroNexes/Novel Pharmaceutics Institute that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Novartis Pharmaceuticals that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Osmotica that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Mallinckrodt that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Sanofi that is relevant to AAN interests or activities. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Hailu Chen has received personal compensation for serving as an employee of Biogen.com. Hailu Chen has received stock or an ownership interest from Biogen.com. Dr. Lewin has received personal compensation for serving as an employee of Biogen. Dr. Lewin has stock in Biogen. Mr. Scaramozza has received personal compensation for serving as an employee of Biogen. Mr. Scaramozza has stock in Biogen. Mr. Scaramozza has received intellectual property interests from a discovery or technology relating to health care. Dr. Bozin has received personal compensation for serving as an employee of Biogen. Dr. Bozin has received personal compensation for serving as an employee of Arvelle Therapeutics. Dr. Bozin has stock in Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Actelion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Fresenius. The institution of Dr. Then Bergh has received research support from Actelion. The institution of Dr. Then Bergh has received research support from Novartis. The institution of Dr. Then Bergh has received research support from DFG (German Science Fund). Dr. Then Bergh has received personal compensation in the range of $10,000-$49,999 for serving as a Member of the Institutional Ethics Board with University of Leipzig, Medical Faculty.

An Interim Analysis of Efficacy and Safety Data in Black and Hispanic Patients With Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (S31.006)

<h3>Objective:</h3> To analyze the interim efficacy and safety data for ocrelizumab (OCR) treatment in Black and Hispanic patients with relapsing multiple sclerosis (pwRMS). <h3>Background:</h3> Black and Hispanic patients are underrepresented in MS trials, and these patients may have higher MS incidence, faster disease progression and/or an increased risk of progression to disability vs White patients. The CHIMES trial (NCT04377555) was designed to evaluate disease activity and OCR response in Black and Hispanic patients. <h3>Design/Methods:</h3> This prospective, open-label, single-arm, Phase IV study included pwRMS who self-identified as Black or Hispanic, were aged 18–65 years and had Expanded Disability Status Scale (EDSS) scores of 0–5.5 points at screening. Patients received two 300-mg OCR infusions 14 days apart, and 600 mg every 24 weeks for 1 year, with an optional 3-year extension. The interim data cutoff was March 30, 2022, with patients who completed 1-year OCR treatment. The primary outcome was no evidence of disease activity (NEDA), defined as the proportion of patients free from a protocol-defined event at Week 48. <h3>Results:</h3> This interim analysis included 49/182 patients enrolled, 36 (73.5%) Black and 13 (26.5%) Hispanic. Mean (SD) age was 33.3 (8.1) years, weight was 90.6 (23.9) kg and 85.7% of patients were female. Patients had a mean (SD) time since first MS symptoms of 3.8 (5.1) years and time since RMS diagnosis was 1.6 (3.4) years. Baseline mean (SD) EDSS score was 2.5 (1.5), Gd-enhancing T1 lesions was 2.5 (3.9) and total T2 lesion volume was 21.7 (21.8) cm³. The proportion of patients with NEDA was 40.8% (95% CI 27.0%–55.8%). Overall, 38 patients experienced ≥1 AE, 3 had a serious AE and 22 had a non-serious infusion-related reaction. No deaths occurred. <h3>Conclusions:</h3> The CHIMES interim analysis provides essential preliminary data for OCR treatment response among Black and Hispanic patients. <b>Disclosure:</b> Dr. Bernitsas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen@Janssen. Dr. Bernitsas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Bernitsas has received research support from Roche/Genentech. The institution of Dr. Reder has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for genentech. Dr. Reder has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for biogen . Dr. Reder has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for serono. Dr. Reder has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NK max. Dr. Reder has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for genentech. Dr. Reder has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for medlink. The institution of Dr. Reder has received research support from genentech. The institution of Dr. Reder has received research support from biogen. The institution of Dr. Reder has received research support from serono. The institution of Dr. Reder has received research support from novartis. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for novartis. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for biogen. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for emd serono. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for genentech. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for sanofi. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for biogen. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for emd serono. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for sanofi. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Chinea has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for allergan. The institution of Dr. Herrman has received research support from Genentech. The institution of Dr. Herrman has received research support from Merck . The institution of Dr. Herrman has received research support from Novartis. Dr. O’Brien has nothing to disclose. Dr. Sater has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffman-LaRoche. Dr. Sater has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Sater has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Sater has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Sater has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Sater has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Sater has received research support from Biogen. The institution of Dr. Sater has received research support from Roche. The institution of Dr. Sater has received research support from EMD Serono. Dr. Amezcua has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for serono. Dr. Amezcua has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Amezcua has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Amezcua has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for genentech. The institution of Dr. Amezcua has received research support from National MS Society. The institution of Dr. Amezcua has received research support from Genentech. The institution of Dr. Amezcua has received research support from Medday. The institution of Dr. Amezcua has received research support from Bristol Myers Squibb Foundation. The institution of Dr. Amezcua has received research support from NIH NINDS. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen Idec. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis Pharmaceuticals. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Williams has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Williams has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Williams has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Meyers Squibb. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis Pharmaceuticals. Dr. Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Janssen. Dr. Williams has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Williams has received publishing royalties from a publication relating to health care. Dr. Williams has a non-compensated relationship as a National Board Member with National MS Society that is relevant to AAN interests or activities. Dr. Wu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Progentec. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Wu has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimmunology. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Department of Justice. Dr. Vartanian has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Vartanian has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Vartanian has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Vartanian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tisch MS Center. Dr. Vartanian has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Jinglan Pei has nothing to disclose. Dr. Acosta has received personal compensation for serving as an employee of Genentech. Nancy Monson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Nancy Monson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Nancy Monson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Nancy Monson has received stock or an ownership interest from TGM Life Sciences, LLC. The institution of Nancy Monson has received research support from NIH. The institution of Nancy Monson has received research support from DOD. Nancy Monson has received intellectual property interests from a discovery or technology relating to health care.

Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study (S46.004)

<h3>Objective:</h3> To report 4-year efficacy and safety data from the ENSEMBLE trial (NCT03085810) of ocrelizumab (OCR) in patients with early-stage relapsing-remitting multiple sclerosis (RRMS). <h3>Background:</h3> Early and sustained treatment of MS with high-efficacy therapy reduces the risk of long-term disease progression. ENSEMBLE is a multicenter, open-label, single-arm Phase IIIb study, evaluating the efficacy and safety of OCR in patients with early-stage RRMS. <h3>Design/Methods:</h3> At the time of enrollment, eligible patients were treatment naive, aged 18–55 years, had an active early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) ≤3.5 and ≥1 clinically reported relapse(s) or ≥1 signs of magnetic resonance imaging (MRI) activity (T1-weighted contrast-enhancing lesions or new/enlarging T2-weighted lesions, with MRI measurements rebaselined at W8) in the prior 12 months. Patients received OCR 600 mg every 24 weeks for 192 weeks. Key endpoints were no evidence of disease activity (NEDA)-3 (defined as no relapses, no 24-week [W] confirmed disability progression [CDP] and no MRI activity), annualized relapse rate (ARR), mean change in EDSS score from baseline (BL) and safety. <h3>Results:</h3> BL characteristics (N=678) were consistent with early-stage RRMS (patients ≤40 years with a median age of 31.0 years; duration since MS symptom onset, 0.78 years; duration since RRMS diagnosis, 0.24 years; mean BL EDSS score [SD], 1.71 [0.95]). At W192, the majority of patients had NEDA (n=394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses and 81.8% had no 24W-CDP. Adjusted ARR at W192 was low, 0.020 (95% CI, 0.015–0.027). No new or unexpected safety signals were observed. <h3>Conclusions:</h3> Disease activity based on clinical and MRI measures was minimal in most patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab, with no new signals. <b>Disclosure:</b> Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck Serono. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for celgene. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for jansen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novartis. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for merck. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for biogen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for celgene. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Roche. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Benedict has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Brystal Mier Squibb. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Benedict has received research support from Genzyme. The institution of Dr. Benedict has received research support from Biogen. The institution of Dr. Benedict has received research support from Bristol Myer Squib. Dr. Benedict has received intellectual property interests from a discovery or technology relating to health care. Prof. Berger has received personal compensation in the range of $10,000-$49,999 for serving as a speaker at scientific meetings and participant of local and international advisory boards with various companies producing and markerting treatments for multiple sclerosis (Almirall, Biogen, Biologix, Bionorica, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme, TG Therapeutics, UCB). William M. Carroll, MBBS, MD, FRACP has nothing to disclose. The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Norwegian MS Society. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Karabudak has nothing to disclose. Joep Killestein has nothing to disclose. Dr. Nos has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche Ltd.. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Almirall, Bayer, Biogen, Bristol Meyers and Squibb Merck, Roche, Sanofi, TEVA. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for University of Catania and AISM/FISM, Fondazione Italiana Sclerosi Multipla. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for Horizon. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for EMD Serono. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for Alexion. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for celgene. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen . Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F Hoffmann La Roche. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Wuerfel has received personal compensation for serving as an employee of MIAC AG. The institution of Dr. Wuerfel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Actelion. The institution of Dr. Wuerfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Wuerfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Thomas Kunzel has received personal compensation for serving as an employee of Roche. Karen Kadner has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Inessa Kulyk has received personal compensation for serving as an employee of Roche. Inessa Kulyk has stock in Roche. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&amp;J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&amp;J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.

Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis (S46.002)

<h3>Objective:</h3> To assess the efficacy and safety of first-line ocrelizumab (OCR) in a subgroup of treatment-naive patients (N=757) with early relapsing multiple sclerosis (RMS) (diagnosis ≤2 years) from the OPERA I/II trials (NCT01247324/NCT01412333) over 9 years of follow-up. <h3>Background:</h3> The benefits and risks of highly effective therapy as first-line treatment early in RMS should inform evidence-based decisions, to improve patient outcomes compared with escalating from low efficacy treatments. <h3>Design/Methods:</h3> Patients were randomized to OCR or interferon (IFN)-β-1a during the 96-week, double-blind period (DBP). In the open-label extension (OLE), patients continued with OCR (OCR–OCR) or switched to OCR (IFN–OCR). Efficacy endpoints included no evidence of disease activity (NEDA) with MRI rebaselining at Week 24 (defined as absence of: Protocol-defined relapses, 24-week confirmed disability progression [24W-CDP], contrast-enhancing T1-weighted and new/enlarging T2-weighted lesions) and annualized relapse rate. Safety measures included incidence/nature of adverse events (AEs) and the association between immunoglobulin (Ig)G below the lower limit of normal (LLN) and serious infections (SIs). <h3>Results:</h3> Of 757 analyzed patients (OCR, 375; IFN, 382), 67% remained on treatment for over 9 years (OCR, 69%; IFN, 65%). During DBP, a higher proportion of OCR-treated patients, compared with IFN, had NEDA (72% vs 44%; p&lt;0.001) and no 24W-CDP (92% vs 88%; p=0.062). In DBP+OLE, OCR–OCR patients had higher rates of NEDA compared with IFN–OCR (48% vs 26%; p&lt;0.001) and no 24W-CDP (79% vs 75%; p=0.2) or relapses (0.05 vs 0.09; p=0.004). Rates of AEs, serious AEs, SIs and malignancies remained low over 9 years of OCR treatment. In DBP+OLE, 1.8% (12/668) of patients reported SIs during periods of IgG &lt;LLN, with comparable types, characteristics and treatment outcomes to the overall SI profile over 9 years. <h3>Conclusions:</h3> In this treatment-naive, early RMS OPERA subgroup, long-term safety and efficacy data over 9 years support the use of ocrelizumab as first-line therapy. <b>Disclosure:</b> Dr. Cerqueira has received personal compensation for serving as an employee of João José Cerqueira Unipessoal Lda. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zambon. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. The institution of Dr. Cerqueira has received research support from Biogen. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche Genentech. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS / Celgene. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Pearson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen . Dr. Pearson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Pearson has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Dr. Pearson has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Pearson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen . Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. The institution of Dr. Traboulsee has received research support from Roche. The institution of Dr. Traboulsee has received research support from Genzyme. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Ziemssen has received research support from Biogen. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics. Corrado Bernasconi has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Roche. Corrado Bernasconi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GeNeuro. Corrado Bernasconi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Santhera. Corey Mandel has received personal compensation for serving as an employee of Genentech. Corey Mandel has received stock or an ownership interest from Genentech. Inessa Kulyk has received personal compensation for serving as an employee of Roche. Inessa Kulyk has stock in Roche. Cathy Chognot has received personal compensation for serving as an employee of Hoffmann-LaRoche LtD. Dr. Schneble has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.. Dr. Schneble has received stock or an ownership interest from F. Hoffmann-La Roche, Ltd.. Kalpesh Prajapati has nothing to disclose. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Actelion. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Havrdova has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen.

Serum NfL in MS Patients Treated with Cladribine: Course and Predictive Value (P1-3.006)

<h3>Objective:</h3> We here aimed to assess the impact of CLAD on serum neurofilament light chain (sNfL), a biomarker for neuroaxonal damage. Moreover, we investigated whether sNfL at baseline and at 12 months from CLAD start can predict treatment response. <h3>Background:</h3> Cladribine (CLAD) acts as semi-selective immune reconstitution therapy (IRT) for patients with multiple sclerosis (MS). As such, short treatment cycles in year one and two promise long-term disease control. <h3>Design/Methods:</h3> We included 14 patients with MS about to start CLAD and assessed sNfL values at baseline (BL) and at the end of the first treatment year (12 months from BL). Long-term clinical and radiological data were extracted from medical records. Disease activity was classified according to relapses, MRI activity and EDSS progression. We also calculated a time to loss of “no evidence of disease activity (NEDA)” analysis to evaluate the predictive value of sNfL. <h3>Results:</h3> Patients (12/14 female, mean age 35 ± 9 years, median EDSS 1.75 range 0 – 3.5) were followed-up for 39 (± 9) months after CLAD start. A breakthrough disease was recorded in 36% (5/14) while 64% had no or mild disease activity. The sNfL was significantly reduced by CLAD therapy (mean: 24,72 pg/ml to 8,75 pg/ml, p = 0.0008) and increased in only one patient (from 4,63 pg/ml to 5,55 pg/ml). SNfL values at BL and 12 months did not correlate with long-term disease control. <h3>Conclusions:</h3> CLAD therapy prevents neuroaxonal damage as reflected by sNfL. Most patients had no or only mild disease progression on long-term outcome. SNfL at the end of the first treatment cycle appears no suitable marker to predict long-term treatment response. <b>Disclosure:</b> Mr. Moser has nothing to disclose. Michael Seiberl has nothing to disclose.

Relapsing-remitting and primary progressive multiple sclerosis treated with ocrelizumab: A comparative study.

To compare the clinical and radiological effectiveness of ocrelizumab in primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) in a clinical practice setting and describe its tolerability and adverse events. A retrospective observational cohort study was conducted comparing clinical and magnetic resonance imaging (MRI) data of all patients with (pw)PPMS and RRMS who had received treatment with ocrelizumab at least one cycle and have been followed up for one year at minimum. 42 patients (27 women) were treated with ocrelizumab: 30 had RRMS and 13 PPMS. The follow-up period was 26.4±8.4 months. The proportion of pwRRMS with no evidence of disease activity (NEDA) in the first year was 69.2% and in the second was 80%. In the first year, radiological activity was reduced by 80.0% in pwRRMS and 91.7% in pwPPMS. In the second year, radiological activity was completely reduced in both groups. A statistically significant difference (p<0.05) was observed between the pre-ocrelizumab rate of disability progression vs. the first year rate of progression for pwRRMS and pwPPMS. However, an increase in the disability progression rate in the second year of treatment was found in pwPPMS. Ocrelizumab was mostly well tolerated and some adverse effects were reported: infusion-related reactions (IRRs) were the most frequent adverse event, followed by infections and hematological side effects. Discontinuations were due to infections, hematological complications, and perception of ineffectiveness. Ocrelizumab was very effective in reducing relapses and MRI activity. The rate of progression was slowed down; however, the effect was more evident for pwRRMS than for pwPPMS over time.

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in multiple sclerosis: preliminary clinical results of approbation of the method

Introduction. In 2018–2020, a study was conducted in the Russian Federation on the efficacy and safety of highdose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT-AHSCT) in multiple sclerosis (MS).The aim of the study was to analyze preliminary data on the effectiveness and safety of the HDIT-AHSCT in patients with MS who participated in the clinical approbation of the method.Material and methods. 21 patients were included in a single-center Pavlov University (Saint Petersburg) observational study. In 10 patients (47.6%) the Expanded Disability Status Scale (EDSS) ranged from 1.0 to 4.0, in 10 — from 4.5 to 6.0 points, 1 patient with primary-progressive MS (PPMS) had 6.5 EDSS points. Cyclophosphamide conditioning regimen (200 mg/kg) in combination with rituximab (1000 mg/m2) was used. Neurological assessment (EDSS, SNRS, T25-FW, 9-HPT, PASAT, MoCA, HADS) and brain MRI were performed before and after 12 months. The early and long-term complications of HDIT-AHSCT were also analyzed.Results. One year after HDIT-AHSCT improvement and significant improvement were noted in 10 patients (47.6%), stabilization — in 8 (38.1%), relapse/progression — in 3 (14.3%). A lower effect was observed in patients with spasticity of more than 3 points by the MAS. According to MRI data 18 patients (85.7%) had stabilization of MS with no disease activity after 1 year, that met the No Evidence of Disease Activity (NEDA) criteria. Long-term complications included autoimmune thyroiditis (n = 1) and amenorrhea in two patients older than 38 years. No TRM were registered during the observation period.Conclusion. HDIT-AHSCT is an effective method of treating patients with multiple sclerosis. The results of the research demonstrate the safety and effectiveness of HDIT-AHSCT and it can be used to expanse the opportunities for providing treatment of patients with MS in the Russian Federation.

Real-Life Experience of the Effects of Cladribine Tablets on Lymphocyte Subsets and Serum Neurofilament Light Chain Levels in Relapsing Multiple Sclerosis Patients.

Although cladribine induces sustained reductions in peripheral T and B lymphocytes, little is known about its effect on axonal damage reduction in multiple sclerosis (MS), which could be demonstrated by assessing the serum neurofilament light chain (sNfL) levels. We investigated the reduction/reconstitution of different lymphocyte subsets (LS) by verifying the correlation with no evidence of disease activity (NEDA) and the variation in sNfL levels during cladribine treatment. We analysed 33 highly active relapsing MS patients and followed them up for 12 ± 3.3 months; blood samples were collected at treatment start (W0) and after 8, 24 and 48 weeks. Seventeen patients (60.7%) showed NEDA during the first treatment. At week 8, we observed a significant decrease in B memory cells, B regulatory 1 CD19+/CD38+ and B regulatory 2 CD19+/CD25+, a significant increase in T regulatory CD4+/CD25+, a slight increase in T cytotoxic CD3+/CD8+ and a non-significant decrease in T helper CD3+/CD4+. Starting from week 24, the B subsets recovered; however, at week 48, CD19+/CD38+ and CD19+/CD25+ reached values near the baseline, while the Bmem were significantly lower. The T cell subsets remained unchanged except for CD4+/CD25+, which increased compared to W0. The LS changes were not predictive of NEDA achievement. The sNfL levels were significantly lower at week 24 (p = 0.046) vs. baseline. These results could demonstrate how cladribine, by inflammatory activity depletion, can also reduce axonal damage, according to the sNfL levels.