Treatment Of Multiple Sclerosis Patients Research Articles

MOG-specific CAR Tregs: a novel approach to treat multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS) with the immune system attacking myelin sheaths leading to neuronal death. While several disease-modifying therapies are available to treat MS, these therapies are not universally effective and do not stop disease progression. More personalized long-term treatment options that target specific aspects of the disease, such as reducing relapse frequency, delaying disability accumulation, and addressing symptoms that impact daily functioning, as well as therapies that can promote neuroprotection and repair are needed. Chimeric Antigen Receptor (CAR) Tcell therapies have revolutionized cancer treatment by intravenously (IV) administering a defined dose of T cells with high specificity provided by the CAR. An autologous CAR T cell therapy using suppressive regulatory T cells (Tregs) inducing long-lasting tolerance would be the ideal treatment for patients. Hence, we expanded the application of CAR-T cells by introducing a CAR into Tregs to treat MS patients. We developed a myelin oligodendrocyte glycoprotein (MOG)-specific CAR Treg cell therapy for patients with MS. MOG is expressed on the outer membrane of the myelin sheath, the insulating layer the forms around nerves, making it an ideal target for CAR Treg therapy. Our lead candidate is a 2nd generation CAR, composed of an anti-MOG scFv screened from a large human library. In vitro, we demonstrated CAR-dependent functionality and showed efficacy in vivo using a passive EAE mouse model. Additionally, the MOG-CAR Tregs have very low tonic signaling with a desirable signal-to-noise ratio resulting in a highly potent CAR. In summary our data suggest that MOG-CAR Tregs are a promising MS treatment option with the potential to induce long-lasting tolerance in patients.

Interferon Signature's Members, a Novel Altered Correlation upon Interferon-β Treatment in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system and is characterized by extensive brain damage and neurodegeneration. Immunological, genetic, and histological analyses of MS patients provide data in support of the concept that autoimmunity plays a crucial role in the condition's course. It has been proposed that MS may be treated with interferon (IFN)-β and other members of the type I family. Low levels of type I IFN in MS patients may affect immunological control, establish the threshold for an IFN therapeutic response, and be"primed" or "fixed" by IFN therapy. This study was conducted as a cross-sectional study. qRT-PCR was used to examine the expression of two critical IFN regulatory genes, IFI44 and MX1, in MS patients receiving IFN-β treatment. The findings demonstrated a considerable rise in the expression of both genes in MS patients treated with IFN-β compared to those newly diagnosed with the illness. In addition, IFI44 and MX1 might be positively associated with their expression after IFN-β therapy and be regarded as IFN-β responsiveness indicators. The IFI44/MX1 axis could act as one of the crucial regulators of the disease following IFN-β treatment.

The Effectiveness of Vitamin D Intake in Improving Symptoms and Relapses of Multiple Sclerosis: A Systematic Review.

There are disagreements over the effectiveness of vitamin D supplementation in treating multiple sclerosis (MS) patients' symptoms and reducing relapses. The goal of this systematic review is to assess the effect of vitamin D supplements on improving symptoms and relapses in MS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted by searching eight databases: Embase, PubMed, Cochrane Library, MEDLINE, CINAHL, Web of Science, Scopus, and Google Scholar. The RoB 2 tool was used to evaluate the quality of the studies that were included in the analysis. From the 1,345 studies identified, 16 randomized controlled trials were selected. All studies reported that vitamin D administration significantly increased the mean serum 25(OH)D compared with the placebo group. Also, most included studies revealed a significant improvement in magnetic resonance imaging (MRI) brain lesion markers. However, most studies showed that being treated with vitamin D instead of placebo showed no significant effect on relapse rates, fatigue, Expanded Disability Status Scale (EDSS), serum neurofilament light chain (NfL), calcium, and cytokine levels, except for quality-of-life transforming growth factor beta (TGF-β). This systematic review shows that the effect of vitamin D supplements on improving symptoms and relapses during treatment in MS patients remains inconclusive.

Enhancing Drug Delivery of Glatiramer Acetate Through In Vitro Development of Controlled-Release Nanoliposomes: Investigating Drug Release Kinetics and Cytotoxic Effects

Background: Multiple sclerosis (MS) damages the myelin sheath covering nerve fibers. This condition affects 400,000 individuals in the United States and 2.5 million people globally, with a higher rate of diagnosis in women aged 20 - 40, with a ratio of 2:1. Liposomes facilitate drug dispersion, making them valuable in biomedicine. They enhance the stability of therapeutic medications, improve cellular and tissue absorption, and increase chemical bioactivity at specific locations. This technique delivers encapsulated compounds with high precision while minimizing negative consequences observed in laboratory settings. Objectives: This study aims to develop an optimal nanoliposome formulation using glatiramer acetate (GA) as the active pharmaceutical ingredient by examining drug release and associated adverse effects to achieve the most effective nanoliposomal system. Methods: The thin layer hydration method was used to prepare nanoliposomes. A comprehensive array of analytical techniques, including FE-SEM, FTIR, XRD, HPLC, and DLS, were employed to examine the physicochemical characteristics of the product. Additionally, the biosafety of the nanoliposomes was assessed using the MTT assay on the 1321N1 human astrocytoma cell line. The release profile of GA from the carrier was studied using the dialysis diffusion method, and the stability of the nanoliposomes was also inspected. Results: The size, Polydispersity Index (PDI), and zeta potential of the nanoliposomes were 91.2 ± 1.3 nm, 0.34 ± 0.03, and -27.3 ± 1.2 mV, respectively. The drug entrapment efficiency (DEE%) in nanoliposomes was approximately 70.2 ± 1.7%. The results from XRD and FTIR revealed no chemical interaction between the drug and carrier, and the nanoliposomes were safe for the cultured cell line. The nanoliposomes were stable under storage conditions and exhibited a sustained release profile. Conclusions: Nanoliposomes, as drug carriers, are known to be a potent drug delivery system due to their numerous advantages. Based on the results, GA-nanoliposomes show promise as a strategy for treating MS patients, pending further in vivo experiments and clinical trials.

Fatigue in multiple sclerosis: can we measure it and can we treat it?

Fatigue is a common and debilitating symptom in multiple sclerosis (MS). However, after over 100 years of inquiry its definition, measurement and understanding remains elusive. This paper describes the challenges clinicians and researchers face when assessing and treating MS patients, as well as our understanding of neural mechanisms involved in fatigue. Challenges for the future are discussed.

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis.

B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE. Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model. The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed. Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.

Efficacy and Safety of Mirabegron Add-on Therapy After Failure With Solifenacin in Multiple Sclerosis Patients With Overactive Bladder: A Pilot Study.

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative progressive disease of central nervous system that mostly affects young adults. (1) Because of involvement of spinal cord and brain, lower urinary dysfunction symptoms are commonly encountered. MS patients mostly show overactive bladder symptoms like urgency, frequent daytime urination, and urgency incontinence. Among MS patients, antimuscarinic therapy is the first-line treatment with overactive bladder symptoms as well as in general population yet 30% of the patients show insufficient improvement or intolerance to the treatment (2). In our study, our aim is to evaluate the efficacy and safety of mirabegron add-on treatment in MS patients after inadequate response to antimuscarinic monotherapy. University of Kyrenia and Dr Burhan Nalbantoglu State hospital's databases were screened for the study. Seventy patients who were residents diagnosed with MS according to McDonald criteria were questioned. Among these patients, a total of 22 of them were included in the study. Inclusion criteria was at least 3 years of MS diagnosis, score of <6 at Expanded Disability Status Scale, and a score of ≥3 at Overactive Bladder Symptom Score Scale. Among selected patients, 10 mg solifenacin treatment was daily started and followed for 4 weeks. Mirabegron add-on treatment was initiated to the 11 patient who had inadequate improvement in overactive bladder symptom score. After mirabegron add-on treatment among 11 patient, there was a sufficient improvement in overactive bladder symptom score ( P < 0.008). In our study, we have found that antimuscarinic and mirabegron combination causes improved efficacy for overactive bladder in MS population.

Discovery of a brain penetrant small molecule antagonist targeting LPA1 receptors to reduce neuroinflammation and promote remyelination in multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease characterized by inflammatory demyelination that disrupts neuronal transmission resulting in neurodegeneration progressive disability. While current treatments focus on immunosuppression to limit inflammation and further myelin loss, no approved therapies effectively promote remyelination to mitigate the progressive disability associated with chronic demyelination. Lysophosphatidic acid (LPA) is a pro-inflammatory lipid that is upregulated in MS patient plasma and cerebrospinal fluid (CSF). LPA activates the LPA1 receptor, resulting in elevated CNS cytokine and chemokine levels, infiltration of immune cells, and microglial/astrocyte activation. This results in a neuroinflammatory response leading to demyelination and suppressed remyelination. A medicinal chemistry effort identified PIPE-791, an oral, brain-penetrant, LPA1 antagonist. PIPE-791 was characterized in vitro and in vivo and was found to be a potent, selective LPA1 antagonist with slow receptor off-rate kinetics. In vitro, PIPE-791 induced OPC differentiation and promoted remyelination following a demyelinating insult. PIPE-791 further mitigated the macrophage-mediated inhibition of OPC differentiation and inhibited microglial and fibroblast activation. In vivo, the compound readily crossed the blood–brain barrier and blocked LPA1 in the CNS after oral dosing. Direct dosing of PIPE-791 in vivo increased oligodendrocyte number, and in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS, we observed that PIPE-791 promoted myelination, reduced neuroinflammation, and restored visual evoked potential latencies (VEP). These findings support targeting LPA1 for remyelination and encourage development of PIPE-791 for treating MS patients with advantages not seen with current immunosuppressive disease modifying therapies.

Torben Fog – A Danish pioneer in a multi-faceted spectrum of multiple sclerosis research

Torben Fog was committed to multiple sclerosis (MS) research for more than four decades, starting before the defence of his thesis in 1948 and lasting until his death in 1987. His research was multi-facetted, making him one of the great pioneers in the study of essential parts of the pathology, immunology and treatment of MS. He has contributed with meticulous studies of the MS plaques, documenting the perivenous distribution of plaques in the spinal cord. He constructed a scoring system for the disability in MS and used a computer programme to calculate a total neurological deficit. Together with his co-workers, Fog in 1972 was the first to report the association between MS and the human leukocyte antigen system. Fog can be considered as the father of immunomodulatory therapy in MS, treating MS patients with the first transfer factor, and as early as 1980, he was the first to treat MS with intramuscular natural interferon.

Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS

To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.

The first experience with the use of divozilimab in the treatment of multiple sclerosis patients in daily clinical practice

The aim of this study is to assess the efficacy and safety of divozilimab in patients who have received post-marketing treatment and participants of clinical trials BCD-132-2 and BCD-132-4 were conducted at the IHB RAS. Additionally, we will present a case report of divozilimab therapy in a patient with highly active multiple sclerosis (MS). The study included 27 patients with MS. We assessed the dynamics of neurological status, magnetic resonance imaging (MRI) findings, and disability level during divozilimab treatment. We also analyzed the incidence and severity of adverse events (AE), including infusion reactions. During treatment with divozilimab, no exacerbations or radiological disease activity were observed after the first six months. Complete clinical remission was achieved in 25 patients. All 12 patients who received the drug as part of post-marketing use met the NEDA-3 criteria, and five of them showed improvement. Most AE were mild, none exceeding grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE). Laboratory parameter changes were also mild and did not exceed I-II grade according to CTCAE. There were no instances of therapy discontinuation due to intolerance. The data from post-registration use of divozilimab confirm the results of clinical trials, showing high efficacy of the drug with a predictable and favorable safety profile.

A based-rule fuzzy expert system to estimate the response to treatments in multiple sclerosis patients

A based-rule fuzzy expert system to estimate the response to treatments in multiple sclerosis patients

The Comparison of General Characteristics and Early and Late Post-intervention Results in Patients With Trigeminal Neuralgia Secondary to Multiple Sclerosis and Idiopathic Trigeminal Neuralgia Treated With Radiofrequency Thermocoagulation.

Aim The aim of this study was to investigate possible differences (in terms of demographic structure, disease history, complaints, clinical findings, early and late treatment outcomes, and complications) between patients with idiopathic trigeminal neuralgia (ITN) and trigeminal neuralgia (TN) secondary to multiple sclerosis (MS) who were admitted to our clinic and underwent radiofrequency (RF) thermocoagulation procedure. Materials and methods Patients who underwent percutaneous radiofrequency thermocoagulation with a diagnosis of trigeminal neuralgia by a single neurosurgeon in a single neurosurgery clinic between January 2005 and January 2020 were included in this study. Patients were divided into two groups: idiopathic trigeminal neuralgia and trigeminal neuralgia secondary to multiple sclerosis (MSTN) according to their diagnosis. In our study, 215 TN patients who underwent 286 procedures were included. These patients were categorized according to age, sex, involved side, pain localization, and pain history. Postoperative complications were determined after each intervention. The early and late results of all interventions were evaluated, and the results were compared between both groups. All results were statistically analyzed. Results Considering the age of the patients, the mean age of the idiopathic group was higher than the multiple sclerosis group (58.18>49.46). In terms of the side of pain, bilateral involvement was significantly more common in the MS secondary group (1.48%<30.77%). There was no significant difference between the early results of both groups. In terms of remission periods, the pain-free period in the MS secondary group was significantly shorter than in the idiopathic group (mean value in months, 30.87>23.81). Conclusion The radiofrequency thermocoagulation of the trigeminal nerve is a highly effective, low-complication, reproducible procedure for trigeminal neuralgia, but the search for ways to improve the efficacy of treatment in MS patients should continue.

Real world study of ocrelizumab in multiple sclerosis: Kuwait experience

BackgroundOcrelizumab is a humanized anti-CD20 antibody that has been approved for the treatment of patients with multiple sclerosis (MS). Real-world data in the Middle East is very limited. ObjectivesTo describe the effectiveness and safety of ocrelizumab treatment in MS patients in a real clinical setting. MethodsThis is an observational, registry-based study. MS patients who were treated with ocrelizumab and completed at least one-year follow-up post-treatment were included. Baseline clinical and radiological characteristics were collected before ocrelizumab initiation. The relapse rate, disability measures, magnetic resonance image (MRI) activity (new T2 lesions and/or GD+ enhancing T1 lesions), and adverse events (AE) at the last follow-up visits were assessed. ResultsData from 447 patients were analyzed, of which 260 (58.2%) were females. The mean age and mean disease duration were 37.39 ± 11.61 and 9.38 ± 7.57 years respectively. Most of the cohort was of a relapsing form (74.3%; n = 332), whereas active secondary and primary progressive forms represented 15.4% (n = 69) and 10.3% (n = 46) respectively. In the relapsing cohort, Ocrelizumab was prescribed in 162 (48.8%) patients due to highly active disease, and in 99 (29.8%) patients due to disease breakthrough while on prior therapies. In the last follow-up visits, most of the relapsing cohort was relapse-free (95.8% vs. 27.4%; p <0.001), had no evidence of MRI activity (3.6% vs. 67.5%; p <0.001) while EDSS score was stable (1.80+1.22 vs. 1.87+1.16; p < 0.104) when compared to baseline. NEDA-3 was achieved in 302 (91%) of RRMS patients. Confirmed disability progression was 27.5% and 23.9% in SPMS and PPMS respectively. Adverse events were observed in 139 (31.1%); infusion reactions and infections represented the most. ConclusionThis study showed that ocrelizumab is an effective and safe treatment for MS patients in a real clinical setting similar to what was observed in clinical trials.

Consensus recommendations on regional interdisciplinary standardization of MRI diagnostics for multiple sclerosis in the metropolitan area of Essen

Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g., for making the diagnosis or treatment monitoring. To address these challenges a group of neurologists and (neuro)radiologists developed a consensus proposal for standardization of image acquisition, interpretation and transmission of results and for improvement in interdisciplinary cooperation. This pilot project in the metropolitan area of Essen used a modified Delphi process and was based on the most up to date scientific knowledge. The recommendation takes the medical, economic, temporal and practical aspects of MRI in MS into consideration. The model of interdisciplinary cooperation between radiologists and neurologists with the aim of a regional standardization of MRI could serve as an example for other regions of Germany in order to optimize MRI for MS.

Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis.

In spite of the advances in therapeutic modalities, morbidity, due to multiple sclerosis (MS), still remains high. Therefore, a large body of research is endeavouring to discover or develop novel therapies with improved efficacy for treating MS patients. In the present study, we examined the immunomodulatory effects of apigenin (Api) on peripheral blood mononuclear cells (PBMCs) isolated from MS patients. We also developed an acetylated form of Api (apigenin- 3-acetate) to improve In its blood-brain barrier (BBB) permeability. Additionally, we compared its anti-inflammatory properties to original Api and methyl-prednisolone-acetate (a standard therapy), as a potential option in treating MS patients. The current study was an experimental-interventional research. The half maximal inhibitory concentration (IC50) values for apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate were determined in healthy volunteers' PBMCs (n=3). Gene expressions of T-box transcription factor (TBX21 or T-bet) and IFN-γ, as well as proliferation of T cells isolated from MS patients' PBMCs (n=5), were examined in co-cultures of apigenin-3-acetate, Api and methyl-prednisolone-acetate after 48 hours of treatment, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings showed that apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate at concentrations of 80, 80, and 2.5 M could inhibit Th1 cell proliferation after 48 hours (P=0.001, P=0.036, and P=0.047, respectively); they also inhibited T-bet (P=0.015, P=0.019, and P=0.022) and interferon-γ (IFN-γ) gene expressions (P=0.0001). Our findings suggested that Api may have anti-inflammatory properties, possibly by inhibiting proliferation of IFN-producing Th1 cells. Moreover, comparative immunomodulatory effects were found for the acetylated version of apigenin-3-acetate versus Api and methyl-prednisolone-acetate.

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.

Safety and efficacy of Cladribine in real life sitting, Kuwait Experience (P8-3.014)

<h3>Objective:</h3> To study the effectiveness and the safety of Cladribine treatment in MS patients in a real-world clinical setting. <h3>Background:</h3> Cladribine was approved for treatment of multiple sclerosis (MS). Real-world data is very limited. <h3>Design/Methods:</h3> This observational, prospective study included MS patients who had at least one year follow-up after second course of Cladribine treatment. Baseline patient clinical and radiological characteristics recorded within one year prior to Cladribine initiation. The relapse rate, disability measures, radiological activity and adverse events at last visit were assessed. <h3>Results:</h3> A total of seventy-two patients, 59 (81.9%) were females, mean age 36.32 ±10.06 years old, mean disease duration 7.21±6.19. Most patients (n=32; 44.4%) were naïve to any treatment. Forty patients (55.6%) completed two courses of treatment. At the end of observational period, most of our cohort was relapse free (85% versus 25%; P&lt;0.001) and few had new T2 lesions (7.5% versus 70.8%; P&lt;0.001 and gadolinium enhancement 5% versus 66.7%; P&lt;0.001) in MRI compared to baseline. ARR was significantly reduced 0.15 ±0.36 versus 0.85±0.53; P&lt;0.01). Most of cohort 90% has no progression of disability. No evidence of disease activity 3 (NEDA-3) was achieved in 30 (75%) patients. It was achieved in 87.5% of naive patients versus 66.7% in patients who received prior disease modification drugs before Cladribine initiation. Infections 6 (n=6; 8.4%) lymphocytopenia (n=3; 4.2%), and elevated liver enzymes (n=1; 1.4%) were reported. <h3>Conclusions:</h3> The effectiveness and safety profile of cladribine in this study were consistent with data of phase 3 clinical trials. Early initiation of cladribine is associated with favorable outcome. <b>Disclosure:</b> Dr. AlMojel has nothing to disclose. Dr. Al-Hashel has nothing to disclose. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Bayer, Novartis, Merck, Roche, Sanofi. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen, Novartis, Merck, Roche, Sanofi. Dr. Ahmed has nothing to disclose.

The Challenges of MRI in Clinical Practice (P11-3.008)

The Challenges of MRI in Clinical Practice (P11-3.008)

Symptom stability throughout Ocrelizumab infusion cycle in patients with Multiple Sclerosis: final results of SYMptom Burden on Ocrelizumab, a Longitudinal Study (SYMBOLS) (P7-3.017)

<h3>Objective:</h3> To determine whether symptom burden in Ocrelizumab (OCR)-treated MS patients varies over the 6-month infusion cycle. <h3>Background:</h3> OCR is a humanized anti-CD20 antibody therapy for multiple sclerosis (MS) given at 6-month intervals. Some patients report an increase in symptoms toward the end of the infusion cycle (“wearing off”). <h3>Design/Methods:</h3> One-year, prospective, observational, two-center study (NCT04855617) enrolled MS patients aged 18–80 with EDSS scores between 0–7 who were treated with OCR for ≥ 1 year or were initiated on OCR. All patients were followed at NYU MS Care Center (NYU), New York, NY, and the Elliot Lewis MS Center (ELC), Wellesley, MA. Patients completed NeuroQol short forms, SymptoMScreen, work productivity (WPAI:MS), and medical screening questionnaires at 4-, 12-, and 24-weeks post-infusion for two consecutive infusion cycles as well as a post-study completion questionnaire. <h3>Results:</h3> 115 participants were included in the study (n=53 NYU/n=62 ELC); 64% were female; 36% - non-White; baseline age - 46.2±12.5 years; disease duration −15.3±10.7 years; OCR treatment duration - 2.54 ±1.04 years; median (IQR) EDSS - 3.0 (1.5, 5.3); EDSS was &gt;= 4 in 48 patients (42%). Paired Wilcoxon nonparametric tests used to evaluate the changes in outcome scores from pre- to post-infusion showed no significant changes on any NeuroQol and SymptoMScreen scales. Scores on two WPAI-MS subscales (“impairment while working due to health” and “overall work impairment”) increased by 10% during the 2^nd cycle (p-values=0.02 and 0.001) but not the 1^st cycle. On the post-completion questionnaire, the percentage of patients who reported ‘wearing off’ always was 4%, usually - 33%, sometimes - 45%, and never - 17%. <h3>Conclusions:</h3> Although symptom burden remained stable throughout two OCR infusion cycles on multiple scales, most patients reported “wearing off” at least sometimes. We will discuss possible explanations for this discrepancy. <b>Disclosure:</b> Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. The institution of Dr. Kister has received research support from Genentech. Dr. Kister has received publishing royalties from a publication relating to health care. Prof. Oh has nothing to disclose. Ms. Douglas has nothing to disclose. Ms. O’Shea has nothing to disclose. An immediate family member of Tamar Bacon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of an immediate family member of Tamar Bacon has received research support from Gentech. An immediate family member of Tamar Bacon has received publishing royalties from a publication relating to health care. Dr. Bouley has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Bouley 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. Bouley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bouley has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Bouley has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Bouley has received research support from Novartis. Dr. Lathi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Katz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Theraputics. The institution of Dr. Katz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen Pharmaceuticals. The institution of Dr. Katz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. The institution of Dr. Katz has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Katz has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Katz has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi-Genzyme. The institution of Dr. Katz has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Genentech. The institution of Dr. Katz has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD-Serono.