¹Jihad Inshasi, ²Amir Boshra, ²Joseph Youssef

¹MS Department, Rashid Hospital and Dubai Medical College, Dubai health Authority, Dubai, UAE; ²Merck Serono Middle East FZ Ltd, an affiliate of Merck KgaA, Darmstadt, Germany.

Background:

The Gulf nations were among the first in the world to implement the COVID-19 vaccination. Regional guidelines like MENACTRIMS endorse that MS patients should be vaccinated against COVID-19. The vaccines being offered in the region include Sinopharm, Pfizer-BioNTech, Sputnik V, and Oxford-AstraZeneca. “Adveva™ Gulf is a Merck-sponsored health care provider (HCP) driven patient support program (PSP) for patients treated with cladribine tablets”

Objectives:

To describe the real-world experience on the use of COVID-19 vaccination in multiple sclerosis (MS) patients treated with cladribine tablets participating in the PSP.

Material(s) and Method(s):

MS patients treated with cladribine tablets and participating in the PSP in the Gulf region were asked to participate in a questionnaire-based survey about their COVID-19 vaccination status.  The interview was initiated by health educators over the phone, and they submitted the answers on the patient’s behalf. Patient’s verbal consent was required to start the questionnaire. Information collected included: Demographic, Treatment dates, Vaccination, and COVID-19 information.

Result(s):

Of the 106 MS patients, 92 (86%) patients provided consent to participate and completed the questionnaire. 77.5% of patients were females. All patients had been on cladribine tablets since 2018-till Sept 2021 (66% in Year 1, 15% in Year 2, and 19% in year 3 and 4). From the time of initiation of cladribine tablets, no switch to another disease modifying drugs (DMD) were observed. Overall, 74 (80.4%) of the cladribine tablets patients had received the COVID-19 vaccine. 51.4% and 41.9% of patients were vaccinated by the Pfizer and Sinopharm vaccines, respectively. Among those vaccinated in Year 1 and 2 (n=59), the mean time between the last dose of cladribine tablets and the first dose of the vaccine was 129 days. Of the patients who had not received the vaccine (n=18), 72.2% were planning to receive the vaccine. Only 2 patients were not willing to receive the vaccine for fear of complications. After completion of the COVID-19 vaccine regimen, 6 (8%) patients were infected with SARS-CoV-2, 5 of them confirmed by the RT-PCR test. All the cases were mild, and none of the patient’s required hospitalization. No safety concerns were reported after the administration of the COVID-19 vaccine. The mean time from the completion of the vaccine series till the development of the SARS-CoV-2 infection was 79 days.

Conclusion(s):

The outcomes of this survey suggest that the use cladribine tablets didn’t hinder the patients from receiving COVID-19 vaccinations. Few patients developed SARS-CoV-2 infection despite being vaccinated, but all had mild disease and did not require hospitalization. No safety concerns were observed. Continuous monitoring will be required to assess the safety and efficacy of the COVID-19 vaccine in this specific population. Meanwhile, MS patients should be encouraged to receive COVID-19 Vaccination.

¹Roya Abolfazli, ²Seyed Massood Nabavi, ³Amirereza Azimi, ⁴Mohammadali Nahayati, ⁵Koroush Gharegozli, ⁶Monireh Ghazaeian, ⁷Hamid Reza Torabi, ⁸Shahrzad Shahrokhi, ¹Sara Samadzadeh

¹Tehran University of Medical Sciences – Amiralam Hospital, Department of Neurology, Tehran, Iran; ²Shahed University of Medical Sciences, Department of Neurology, Tehran, Iran; ³Tehran University of Medical Sciences, Sina Hospital, Multiple Sclerosis Research Center, Tehran, Iran; ⁴Mashhad University of Medical Sciences, Department of Neurology, Mashhad, Iran; ⁵Shahid Beheshti University of Medical Sciences, Department of Neurology, Tehran, Iran; ⁶Mazandaran University of Medical Sciences – Faculty of Pharmacy, Department of Clinical Pharmacy, Sari, Iran; ⁷Jam Hospital, Tehran, Iran; ⁸Zistdaru Danesh Pharmaceutical Company, Medical Department, Tehran, Iran

Background:

Patient-reported outcomes (PROs) is a useful way to determine the various effects of disease modifying therapy (DMT) on patients daily lives and their disease course. This study aimed to evaluate the patients’ treatment satisfaction after switching to a brand-generic Teriflunomide product (Tebazio®, 14 mg tablet) produced by Zistdaru Danesh biopharmaceutical company and report the tolerability and safety concerns during the period of the treatment.

Material(s) and Method(s):

The study was conducted on patients with confirmed diagnosis of multiple sclerosis (MS) as defined by the Revised McDonald Criteria (2015) from Nov 2019 to Nov 2020. They were ambulatory with a EDSS of 0 to 5.5, and their treatment by Teriflunomide 14 mg was just started. Study outcomes included patients’ satisfaction was measured by Treatment Satisfaction Questionnaire for Medication [Version 1.4] (TSQM) at baseline and week 24, disability status measured by Expanded Disability Status Scale [EDSS] score at baseline and week 24, safety and tolerability evaluated over 6 months.

Result(s):

Of 200 patients enrolled, 100 patients completed the study protocol and evaluated. Patients reported significant improvements in treatment satisfaction scores of convenience and side effects domains of TSQM scores at week 24 following the switch to teriflunomide (Effectiveness: baseline, 66.53, Week 24, 68.97; Convenience: baseline, 66.31, Week 24, 78.97; Side effect: baseline, 67.13, Week 24, 75.60; Overall Satisfaction: baseline, 63 Week 24, 65.42; P < 0.001 in all comparisons). The most common adverse drug reactions were hair thinning (36%), dermatologic (17%), gastrointestinal (23%), liver function test (LFT) dysfunction (11%), and neurologic side effects (9%) which rarely caused treatment discontinuation.

Conclusion(s):

Patients reported significant satisfaction regarding TSQM scores after switching to Tebazio at week 24 which can be impressive to increase patient compliance. The 14 mg brand-generic Teriflunomide product was well tolerated in Iranian RRMS patients and no new alarming signal was detected during the study period.

¹Gavin Giovannoni, ²Thomas Leist, ³Aida Aydemir, ³Elisabetta Verdun Di Cantogno

¹Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; ²Division of Clinical Neuroimmunology, Jefferson University, Philadelphia, United States; ³EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, United States

Background:

CLASSIC-MS (NCT03961204) was an exploratory, ambispective Phase IV study designed to evaluate the long-term efficacy of cladribine tablets (CladT) in the real-world setting, for patients with relapsing multiple sclerosis (MS) who were previously enrolled to Phase III (parent) trials. The objective of this investigation was to report primary results for CLASSIC-MS in terms of long-term mobility and disability beyond the treatment courses that patients received in the parent trials, with the aim of informing future treatment approaches.

Material(s) and Method(s):

This analysis represents patients in CLASSIC-MS who participated in the Phase III CLARITY trial whether or not they participated in CLARITY Extension, and who had received ≥1 course of CladT or placebo. The primary objective of CLASSIC-MS was the evaluation of long-term mobility (no wheelchair use/bedridden; i.e. EDSS <7 in the 3 months prior to first visit in CLASSIC-MS). The main secondary objective was long-term disability status (no requirement for an ambulatory device; i.e. EDSS <6 any time since last parent study dose [LPSD]). Analyses are descriptive and shown in relation to exposed/never exposed to CladT in CLARITY.

Result(s):

The CLASSIC-MS population who previously participated in CLARITY/CLARITY Extension comprised 435 patients with relapsing MS (67.8% female; mean±SD EDSS score, 3.87±2.07 at CLASSIC-MS baseline), with a median time since LPSD of 10.9 (range 9.3–14.9) years and a median disease duration of 20.7 (range 13.9–46.5) years at CLASSIC-MS baseline. A total of 90.6% (n=394) were exposed to CladT during CLARITY/CLARITY Extension, including 160 patients who received the approved cumulative dose of 3.5 mg/kg over 2 years; the remaining 9.4% (n=41) were never exposed. The proportion of patients not using a wheelchair/bedridden in the 3 months prior to CLASSIC-MS (i.e. EDSS <7) was 90.0% of the CladT exposed cohort and 77.8% of the never exposed cohort. Regarding long-term disability status, the proportion of patients with no requirement for an ambulatory device (i.e. EDSS <6) was 81.2% of the CladT exposed and 75.6% of the never exposed cohorts, respectively.

Conclusion(s):

Baseline patient characteristics suggest that patients enrolled in CLASSIC-MS were a representative sample of all patients included in the original parent studies. Reported findings for CLASSIC-MS, with a median of 10.9 years’ follow-up after CLARITY/CLARITY Extension, suggests sustained efficacy of CladT in terms of long-term mobility and disability status.

¹Bassem Yamout, ²Kerstin Hellwig, ³Riley Bove, ⁴Pranava Katkuri, ⁵Ulf Schulze Topphoff, ⁶Dee Stoneman, ⁷Ronald Zielman, ⁸Ratnakar Pingili, ⁹Maria K. Houtchens

¹Neurology Institute and Multiple Sclerosis Center, Harley Street Medical Centre, Abu Dhabi, UAE; ²Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany; ³University of California San Francisco, San Francisco, CA, USA; ⁴Novartis Pharmaceuticals Pvt. Ltd., Hyderabad, India; ⁵Novartis Pharma GmbH, Nuremberg, Germany; ⁶Novartis Pharma AG, Basel, Switzerland; ⁷Novartis Pharma B.V., Amsterdam, Netherlands; ⁸Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; ⁹Brigham Multiple Sclerosis Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Background:

Ofatumumab, a fully human anti-CD20 monoclonal antibody, is approved for the treatment of relapsing multiple sclerosis (RMS) in adults. As per the ofatumumab label, females of childbearing potential should use effective contraception during and for at least 6 months after discontinuation of treatment. Data on the effect of ofatumumab on pregnancy outcomes are limited in humans. Based on the current knowledge, the maternal-fetal transfer of IgG during the first trimester is minimal and fetal IgG concentration starts to rise from the second trimester. Furthermore, in cynomolgus monkeys, exposure to ofatumumab during gestation did not cause maternal toxicity and there were no adverse effects on the pre- or postnatal development.

Objective(s):

To report pregnancy outcomes from the Novartis Safety Database in women with RMS inadvertently exposed to ofatumumab during pregnancy.

Material(s) and Method(s):

Pregnancy outcomes data from women with RMS exposed to ofatumumab during pregnancy or 6 months prior to last menstrual period were analyzed from clinical trials, and real-world setting in the Novartis Safety Database (cutoff: August 31, 2021). Maternal and infant outcomes including birth defects, congenital anomalies, infections, vaccination, and developmental delays were collected from the reporting of pregnancy up to 1 year of infant age.

Result(s):

As of cutoff date, 32 pregnancies with ofatumumab (ASCLEPIOS I/II, n=4; ALITHIOS, n=14; MIRROR, n=7; post-marketing, n=7) were reported in women with MS; of which 5 were ongoing and in 4 pregnancies, information on the outcomes was not reported. The remaining 23 pregnancies had the following outcomes: therapeutic/induced abortions (n=6), spontaneous abortion (n=5), early intrauterine fetal demise at ~8.5 weeks gestation and patient underwent therapeutic abortion (n=1; not suspected to be related to ofatumumab by the treating physician), and 11 live births of normal babies. Based on followed-up data (up to 1 year of infant age), no B-cell depletion, immunoglobulin/hematological/fetal abnormalities, and serious infections were reported.

Conclusion(s):

In this analysis, no birth defects or congenital anomalies were reported in 23 pregnant women exposed to ofatumumab with known outcomes. There were no reports of B-cell depletion, immunoglobulin/hematological abnormalities, or serious infections in live births to date. Sharing the up-to-date data on pregnancy and infant outcomes with ofatumumab is helpful in counseling women with MS of childbearing potential. A prospective observational registry on maternal and infant outcomes in women exposed to ofatumumab is currently being planned.

¹Sharareh Eskandarieh, ¹Mohammad Ali Sahraian, ¹Vahid Shaygannejad, ¹Abdorreza Naser Moghadasi, ¹Fereshteh Ashtari, ¹Hamidreza Ghalyanchi, ¹Seyed Mohammad Baghbanian, ¹Hossein Mozhdehipanah, ¹Nastaran Majdinasab, ¹Samaneh Houseini, ¹Maryam Poursadeghfard, ¹Nahid Beladimoghadam, ¹Nazanin Razazian , ¹Zhila Maghbooli

¹Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Background:

Recent Covid-19 outbreak around the world turned into an international public health concern. Generally, people who receives immunosuppressive treatments or have an underlying disease are more likely to be infected. Multiple sclerosis (MS) patients also may have higher risk of infection due to the taking immunosuppressive or immunomodulatory drugs (1).

Objective(s):

To identify the epidemiological characteristics of Covid-19 in patients with MS for improve quality of care and achievement to better diagnosis and treatment in MS patients in Iran.

Material(s) and Method(s):

The present data were obtained from a hospital-based registry in Imam Khomeini hospital, Tehran, Iran. Totally, 88 MS patients who was infected by Covid-19 were registered from May, 2020 to March 2021. Demographic and clinical data was collected (2).

Result(s):

55 (65.5%) of participants were female by the mean age (SD) of 37.48 ± 10.05 years. Covid-19 diagnosis of 4 (4.5%) of patients was based on positive PCR test. The most MS treatment was receiving by patients was Rituximab (20 (22.7%)) following by Dimethyl Fumarate (14 (15.9%)), Fingolimod (10 (11.4%)), Glatiramer acetate (8 (9.1%)), Interferon β-1a (IM) (5 (5.7%)), Interferon β-1a (SQ) (5 (5.7%)), Interferon β-1b (3 (3.4%)), Triflunomide (2 (2.3%)) and Natalizumab (1 (1.1%)). The mean (SD) interval from the last Rituximab injection to Covid-19 infection was 3.80 ± 3.40 months. 37 (42.0%) MS patients continued to take their drugs after Covid-19 infection, while 10 (11.4%) of them stopped taking MS medicine and 7 (8.0%) of them was taking no treatment for controlling MS. 2 (2.3%) of participants was diagnosed by MS after Covid-19 infection. 9 (9.7%) subjects hospitalized due to Covid-19 infection. The mean (SD) duration of hospitalization was 5 ± 7.81 days. One (1.1%) death cases was reported.

Conclusion(s):

Our findings revealed valuable data of Covid-19 characteristics in patients with MS which could be useful for improving health services for MS patients during the Covid-19 pandemic (3-4).

¹Amr Abdelsalam, ²Rasha Elkabany, ²Ibrahim Alahmar, ²Mona Sabry

¹Nasser institute for research and treatment, Cairo, Egypt; ²Menoufia University, Menoufia, Egypt

Objective(s):

To realize the degree of DMT adherence among MS patients in Egypt. To find the barriers contributing to medication adherence. To evaluate the clinical impact of non-adherence on MS patients.

Material(s) and Method(s):

This cross-sectional study was carried out on 150 MS patients from MS unit at Menoufia university hospitals and Nasser institute for research and treatment hospital. The degree of adherence was measured using the Arabic version of eight-item Morisky Medication Adherence Scale (MMAS-8). Other related variables were measured by a questionnaire including socio-demographic data, disease characteristics and previous treatment data.

Result(s):

A total of 150 MS patients were included with mean age ± standard deviation of 32.5±8 years and 78% females. The degree of adherence was (59%). The adherence to DMT was significantly affected by the DMT type and route of administration, MS phenotypes, line of treatment and patient satisfaction (P<0.05). However, the adherence was not affected by degree of disability measured by patients’ current EDSS, median (3.415) in adherent patients and (3.395) in non-adherent patients. The most common causes of non-adherence were forgetfulness (40.3%) and injection site reaction/flu like symptoms (38.7 %). Non-adherent patients had higher number of recurrent hospitalization and relapses (median, 1 vs. 0 times, P<0.05) and shorter time from the last hospitalization compared to adherent patient (mean, 10.5 vs. 14 months, P<0.05).

Conclusion(s):

Many factors affect Adherence to DMT and Non-adherent patients experienced significantly more relapse rate and recurrent hospitalization.

¹Maryam Poursadeghfard, ¹Mozhgan Sattar, ¹Mahnaz Bayat

¹Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Background:

Mood disorders are the most concurrent problems in multiple sclerosis (MS) that have a great influence on the quality of life of these patients.

Objective(s):

Disease-modifying drugs (DMDs) could have some positive or negative psychological effects. Rituximab is a drug commonly used as DMD in MS and its effects on mood have not been fully elucidated.

Aim:

In this study, we evaluated the effect of rituximab on mood in MS patients.

Material(s) and Method(s):

In this prospective study, all patients who were going to receives the first dose of rituximab from January 2019 to April 2020 in Fars province, south of Iran were enrolled. HADS questionnaires were filled out before treatment, 3 months after the first course, and 1 month after the second course (7 months later). Data entry and analysis were done using SPSS version 22.

Result(s):

From 108 patients who filled out the questionnaire, 70 patients had inclusion criteria. Mean differences of the HADS scale for depression were 0.54 (CI: -0.24- 1.33; p=0.17) after the first and 0.73 (CI; -0.49-1.55; p=0.30) after the second course of rituximab regarding the base scale which were not significant. For the anxiety, the mean scale at baseline was 6.6 which significantly decreased to 5.6 (p-value= 0.039) after the first and 5.3 (p-value=0.005) after the second course.

Conclusion(s):

According to this study, rituximab could have positive effects on both anxiety (statistically and clinically) and depression (clinically) in M.S patients. As a result of our data, only one dose of rituximab could improve significantly the anxiety of these patients.

¹Jacqueline Nicholas, ²Nick Belviso, ²Geentanjoli Banerjee, ²Caroline Geremakis, ²Robin Avila, ²Karthik Bodhinathan

¹OhioHealth MS Center, Riverside Methodist Hospital, Columbus, United States; ²Biogen, Cambridge, United States

Background:

Natalizumab (NTZ) and ocrelizumab (OCR) are high-efficacy disease-modifying therapies (DMTs) approved to treat relapsing forms of multiple sclerosis (MS). Real-world head-to-head data comparing relapses and related hospitalization rates for high-efficacy DMTs, including NTZ vs OCR, are limited. To compare claims-based relapses and relapse-related hospitalization rates for MS patients treated with NTZ or OCR using data from a large insurance claims database.

Material(s) and Method(s):

This retrospective analysis of the Optum claims database included patients with a diagnosis of MS (≥1 inpatient or ≥2 outpatient claims of International Classification of Diseases [ICD]-9 340 or ICD-10 G35 between 1 April 2017 and 30 September 2020), were naive to study DMTs in the year prior to the initial prescription (index date), and were treated with NTZ or OCR during the study period. Relapses included outpatient events with an MS diagnosis code followed by steroid use within 7 days and hospitalization events with MS as the primary diagnosis code. Inverse probability weighting (IPW) was used to adjust for differences between groups in 17 baseline covariates, including age, number of MS symptoms, prior DMT use, comorbidities, and baseline (index) costs.

Result(s):

The analysis included 835 NTZ and 3497 OCR patients. After IPW, NTZ (n=4342) and OCR (n=4333) patients were well balanced with all standardized differences ≤0.1. Mean follow-up time was approximately 0.9 and 1.0 years for NTZ and OCR patients, respectively. NTZ patients had longer time to first relapse vs OCR with hazard ratio (HR) significantly favoring NTZ (0.70 [95% confidence interval (CI): 0.55–0.88]; P<0.01). The HR for time to first MS-related emergency room (ER) visit did not differ significantly between groups. Mean annualized rates were significantly lower with NTZ than with OCR for any relapse (0.30 vs 0.43; mean difference: –0.13 [95% CI: –0.25, –0.02]; P=0.02) and outpatient relapse (0.22 vs 0.36; mean difference: –0.14 [95% CI: –0.24, –0.04]; P=0.01); but did not differ for MS-related ER visits (0.09 vs 0.08; P=0.82) and relapse-related hospitalizations (0.07 vs 0.07; P=0.83).

Conclusion(s):

Rates of relapses overall were significantly lower with NTZ than with OCR. Though relapses were insurance claims-based and not physician reported, these results provide a direct comparison of relapse-related outcomes and healthcare utilization in MS patients treated with NTZ or OCR in real-world settings.

¹Yousef Saleh Aldughaythir, ¹Mazen Sulaiman Alamr

¹King Fahad Medical City, Riyadh, Saudi Arabia

Background:

Progressive multifocal leukoencephalopathy (PML) is a fatal, rare viral infection of the brain that leads to demyelination and neuronal loss. It develops almost exclusively in patients with a compromised cell-mediated immunity with conditions like acquired immunodeficiency syndrome, hematologic malignancies and treatment with immunosuppression. No treatment is available to reveres or halt the progression of the disease. Pembrolizumab is a monoclonal antibody to programmed cell death-1 (PD-1) protein, inhibiting PD-1 activity allows proliferation of T-cells and enhancing the immune function. Few studies reported the use of pembrolizumab in patients with PML which showed variable response in restoring immune function and halting disease progression.

Material(s) and Method(s):

A single dose of pembrolizumab 2 mg/kg was administered to a patient with PML secondary to treatment of diffuse large B-cell lymphoma. She completed 6 cycles of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and presented 6 months later with progressive neurologic symptoms of behavioral changes, dysarthria, gait difficulty and left sided weakness. MRI brain reveled asymmetric, confluent, non-enhancing bifrontal white matter T2/FLAIR lesions with no mass effect, edema and no diffusion restriction. PCR of cerebrospinal fluid confirmed the presence of JC virus DNA.

Result(s):

Five weeks following administration of pembrolizumab, her neurologic status deteriorated, she was not producing words, not following commands, developed dysphagia, spastic quadriplegia and generalized seizures. Eventually she was pronouncing dead due to asystole.

Conclusion(s):

The unfortunate rapid progression of the disease in this patient prevented the planned treatment regimen of 3 doses separated by 6 weeks. We are hoping that this case will encourage further investigation into this untreatable fatal disease.

¹Raed Alroughani, ²Samar Farouk Ahmed, ³Amr Abokoura, ⁴Essam Alsultan, ⁵Amir Boshra, ⁵Rawan Alcharif, ⁶Rita Ojeil, ⁷Sujata Basu

¹Department of Medicine, Amiri Hospital, Sharq, Kuwait, Neurology Department, ²Neurology Department, Ibn Sina Hospital, Kuwait, Neuropsychiatry Department, Faculty of Medicine, Minia University, Egypt, ³Neurology Division, Mubarak Alkabeer hospital, Kuwait, ⁴Head of Pharmacy Department, Ibn Sina hospital, Kuwait ⁵Merck Serono Middle East FZ LTD, an affiliate of Merck KgaA, Darmstadt, Germany, ⁶HEOR, IQVIA, Middle East, ⁷HEOR, IQVIA, India.

Introduction/Objective(s):

Multiple sclerosis (MS) is a chronic demyelinating neurological disorder characterized by the loss of sensory and motor functions. In 2019, the estimated prevalence and incidence of MS in Kuwait per 100,000 people was 104.9 and 5.39, respectively. Cladribine tablets are the first oral short-course treatment approved for highly active relapsing multiple sclerosis across various geographies. The objective of the study was to estimate the budget impact (BI) of introducing Cladribine tablets compared to other disease-modifying drugs for the treatment of high-disease activity (HDA) relapsing MS patients from the payer’s perspective in Kuwait.

Material(s) and Method(s):

BI analysis was conducted using an excel-based BI model in the adult population with HDA relapsing MS in Kuwait. Three scenarios, ‘MS Treatments without Cladribine’ and ‘MS Treatments including Cladribine’ and ‘MS Treatments with 100% Cladribine’ were assessed over a five-year time horizon. Model inputs included the total number of RRMS and HDA patients, market shares for the three scenarios, and costs associated with drug acquisition, administration, monitoring, adverse events management, and relapse therapy. All costs were presented in 2021 Kuwaiti Dinars (KWD). Inputs were retrieved from literature and/or obtained from interviews with key experts in Kuwait. All the inputs used in the model were further validated by key experts.

Result(s):

Introducing Cladribine tablets for the treatment of HDA relapsing MS in Kuwait resulted in an estimated decrease in the overall net budget from 4.8% (KWD 984,282) in scenario 2 and up to 28.5% ([RB1] KWD 5,861,086) in scenario 3. The major contributors for cost savings included the drug acquisition costs, expenditure associated with adverse events and rescue treatment.

Conclusion(s):

Introduction of cladribine tablets in Kuwait as a treatment option in HDA relapsing MS patients shows cost-saving from the payer’s perspective. The savings in budget improved with an increase in the cladribine tablets market share.

¹John Foley, ²Gilles Defer, ³Lana Zhovtis Ryerson, ⁴Jeffrey A. Cohen, ⁵Douglas L. Arnold, ⁶Helmut Butzkueven, ⁷Gary Cutter, ⁸Gavin Giovannoni, ⁹Joep Killestein, ¹⁰Heinz Wiendl, ¹¹Karen Smirnakis,¹¹Shan Xiao,¹¹George Kong,¹²Robert Kuhelj,¹¹Nolan Campbell

¹Rocky Mountain MS Clinic, Salt Lake City, United States; ²Department of Neurology, Centre Hospitalier Universitaire de Caen, Caen, France; ³Department of Neurology, NYU Langone Health, New York University, New York, United States; ⁴Cleveland Clinic, Cleveland, United States; ⁵Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; ⁶Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Canada; ⁷University of Alabama School of Public Health, Birmingham, United States; ⁸Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; ⁹Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; ¹⁰Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany; ¹¹Biogen, Cambridge, MA, USA; ¹²Biogen, Baar, Switzerland

Background:

Natalizumab 4-week dosing (Q4W) with 300 mg is approved for treatment of relapsing-remitting multiple sclerosis. Dosing frequency of approximately 6 weeks (Q6W) is associated with lower progressive multifocal leukoencephalopathy (PML) risk in retrospective analyses. Real-world data suggest similar effectiveness, but NOVA is the first randomized trial to assess Q6W efficacy. The objective of NOVA was to evaluate the efficacy of natalizumab Q6W in patients previously treated with natalizumab Q4W for ≥12 months compared with continuation of Q4W over 72 weeks.

Material(s) and Method(s):

NOVA is a randomized, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months and had no enhancing lesions at screening. Patients were randomized 1:1 to Q6W or Q4W arms. The primary endpoint was number of new/newly enlarging T2 (N/NET2) hyperintense lesions analyzed by negative binomial regression with baseline (BL) weight, prior natalizumab exposure, and region as covariates. Secondary endpoints included relapses and 24-week confirmed disability worsening (CDW). Primary estimand used all observed data; secondary estimand treated post-intercurrent event data as missing. Missing data were imputed by worst value on treatment or multiple imputation depending on discontinuation reason.

Result(s):

195/248 (79%) Q4W patients and 207/251 (82%) Q6W patients completed NOVA. BL characteristics were well balanced. Proportions of patients with N/NET2 lesions among observed data were low in both arms (Q4W:4.1%; Q6W:4.3%). Mean N/NET2 lesions in the Q4W and Q6W arms with the primary estimand were 0.05 and 0.20 (P=0.0755) and 0.06 and 0.31 (P=0.0437) with the secondary estimand. The difference was mainly due to 2 Q6W patients with high values: (1) 30 lesions that occurred 3 months after natalizumab discontinuation and (2) 25 lesions that occurred with asymptomatic PML observed at week 72. The sum of all other N/NET2 lesions in NOVA was 18 with no other patient having >2. Relapse occurred in 2.1% and 2.8% (P=0.64) and CDW occurred in 8% and 10% (P=0.40) of patients in the Q4W and Q6W arms, respectively. Safety data were consistent with the known drug profile and similar between groups.

Conclusion(s):

Despite a small difference in efficacy between arms, NOVA data suggest the vast majority of patients stable on Q4W dosing can switch to Q6W dosing with no clinically meaningful loss of efficacy. No conclusions on PML risk can be drawn from NOVA.

*Additional authors: Karen Smirnakis (Biogen, Cambridge, USA); Shan Xiao (Biogen, Cambridge, USA); George Kong (Biogen, Cambridge, USA); Robert Kuhelj (Biogen, Baar, Switzerland); Nolan Campbell Biogen, Cambridge, USA).

¹Carrie M. Hersh, ²Carl De Moor, ³Deborah M. Miller, ²Robin Avila, ²James R. Williams, ⁴Kathryn C. Fitzgerald, ²Menglan Pang, ³Marisa P. Mcginley, ⁵Megan Hyland, ⁶Tjalf Ziemssen, ⁷Irene Koulinska

¹Mellen Program for MS, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, United States; ²Biogen, Cambridge, United States; ³Mellen Center, Cleveland Clinic, Cleveland, United States; ⁴Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; ⁵Department of Neurology, University of Rochester Medical Center, Rochester, United States; ⁶University Clinic Carl-Gustav Carus, Dresden, Dresden, Germany; ⁷Biogen, at the time of this study, Cambridge, United States

Background:

Understanding patient-reported changes in physical, mental, and social health after initiation of multiple sclerosis (MS) disease-modifying therapy (DMT) is important to optimize treatment.

Objective(s):

To compare time to improvement in each Quality of Life in Neurological Disorders (Neuro-QoL [NQ]) domain in patients treated with natalizumab (NAT) vs ocrelizumab (OCR).

Material(s) and Method(s):

T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. Baseline (BL) was defined as the last NQ measurement ≤1 year prior to initiating NAT or OCR, and eligible patients had >1 follow-up NQ assessment after initiation of NAT or OCR. Patients with primary progressive MS, prior NAT or OCR therapy, and/or a BL NQ score <5 points below the maximum (for positively worded domains) or <5 points above the minimum (for negatively worded domains) were excluded. T-score improvements of ≥5 points from BL were considered clinically meaningful. Time to first ≥5-point NQ improvement in propensity score (PS)–matched NAT and OCR patients was compared using a semiparametric accelerated failure time model for interval-censored data. BL variables for PS matching included age, sex, race, years of education, MS duration, prior DMT, self-reported disability and relapses in prior year, processing speed and manual dexterity test scores, co-medications, and corresponding NQ domain scores.

Result(s):

There were 146 NAT and 632 OCR patients eligible for this analysis. Mean (standard deviation) follow-up times were 1.1 (0.7) and 1.2 (0.7) years for NAT- and OCR-treated patients, respectively. After exclusion based on BL NQ scores, 88–139 NAT and OCR patients were PS matched, depending on NQ domain. For matched patients, time to improvement was significantly shorter with NAT than with OCR for cognitive function (event time ratio: 0.45; P=0.002) and satisfaction with social roles and activities (event time ratio: 0.47; P=0.04). There were no significant differences between groups in the remaining 10 NQ domains.

Conclusion(s):

NAT treatment can shorten the time to clinically meaningful improvement in the NQ domains of cognition and satisfaction with social roles and activities compared with OCR. These results complement previous findings from MS PATHS indicating that NAT treatment can produce meaningful improvements in mental and social health, with overall annualized improvement rates higher than those observed with OCR.

*Additional authors: Irene Koulinska (Biogen, Cambridge, MA, USA, at the time of this study)

^1,2Kholoud M. Al-Otaibi, ^3,4Badrah S Alghamdi, ¹Maryam A. Al-Ghamdi, ¹Ulfat Omar

¹Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; ²Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia; ³Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; ⁴Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

Introduction:

Multiple sclerosis (MS) is a chronic demyelination disease of the central nervous system (CNS) that attacks the myelin sheath around the axon and damages it. Therefore, promoting remyelination is a critical strategy for treating MS to resolve and alleviate symptoms and protect myelin sheath from further damage. Vitamin D3 (Vit D3) supplementation is increasingly advised to patients with MS. Thus, this study aimed to investigate the effects of Vit D3 supplementation to improve remyelination in a cuprizone (CPZ) mouse model of MS.

Material(s) and Method(s):

The study was designed as two stages (de and re-myelination) for nine weeks; a total of 45 male SWR/J mice were divided into two groups, Control (n=15) and CPZ (n=30) groups for the first five weeks (demyelination stage). Mice in the control group were received a normal diet with ad libitum access through all experiment stages (de and re-myelination), whereas mice in the CPZ group were fed a diet mixed with 0.3% CPZ for 5 weeks to induce demyelination. After week 5 CPZ diet was discontinued and followed by a normal diet for the last 4 weeks (remyelination stages), and mice in the CPZ group were re-divided into two groups: untreated and treated with Vit D3 orally once daily at 800 IU/kg. The effect of Vit D3 on behavioral changes was determined using grip strength meter and rotarod test. The degree of de and re-myelination in the corpus callosum (CC) of brains were assessed by Luxol Fast Blue (LFB) stain at weeks 5, 7, and 9.

Result(s):

The results showed that CPZ significantly reduced behavior performance in mice and myelin content in CC during the demyelination stage. In contrast, mice’s grip strength and motor coordination performance revealed significantly improved behavior after treatment with Vit D3 at early and last remyelination stages (7 and 9 weeks, respectively). Furthermore, LFB staining showed that Vit D3 significantly promoted remyelination in the CC of the brain compared to the untreated group at the remyelination stages.

Conclusion(s):

In conclusion, these results demonstrated that Vit D3 could improve remyelination in a CPZ-demyelinating mouse model of MS.

¹Alessandra Solari, ²Xavier Montalban, ^3,4Jeannette Lechner-Scott, ⁵Fredrik Piehl, ⁶Bruno Brochet, ⁷Dawn Langdon, ⁸Raymond Hupperts, ⁹Krzysztof Selmaj, ¹⁰Eva K. Havrdova, ¹¹Francesco Patti, ¹²Luis Brieva, ¹³Eva Maria Maida, ¹⁴Nektaria Alexandri, ¹⁴Paul Kamudoni, ¹⁴Axel Nolting, ¹⁴Birgit Keller

¹Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; ²Department of Neurology-Neuroimmunology Centre of Multiple Sclerosis of Catalonia (Cemcat), University Hospital Vall d’Hebron, Barcelona, Spain; ³University of Newcastle, Newcastle, NSW, Australia; ⁴Division of Neurology, John Hunter Hospital, Newcastle, NSW, Australia; ⁵Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; ⁶INSERM U 1215, University of Bordeaux, Bordeaux, France; ⁷Department of Psychology, Royal Holloway, University of London, Egham, UK; ⁸Zuyderland Medisch Centrum Sittard, Maastricht University Medical Center, Maastricht, The Netherlands; ⁹Center for Neurology, Lodz, Poland; ¹⁰Charles University, First Medical Faculty, Prague, Czech Republic; ¹¹Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, and Azienda Ospedaliero Universitaria Policlinico “G Rodolico”- San Marco, University of Catania, Italy; ¹²IRBLLEIDA, Hospital Arnau de Vilanova, Lérida, Spain; ¹³Multiple Sclerosis Center, Vienna, Austria; ¹⁴Merck Healthcare KGaA, Darmstadt, Germany

Background/Objective(s):

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system affecting young adults. It is considered one of the major causes of disability in adults. The prevalence of MS is increasing globally. In Saudi Arabia (KSA) it is reported that the projected overall prevalence of MS is 40/100,000 for the total population and higher for Saudi nationals at 61.95/100,000 putting Saudi Arabia above the low-risk zone as per Kurtzke classification (1). With this rising prevalence, and the established significance of multidisciplinary team management, there is a growing need for specialist MS nurses. A group of specialized MS nurses formed an advisory group to support the role of the MS nurse in the management of patients with MS in KSA. This is the first advisory board meeting aiming to optimize nursing care for MS patients in KSA.

Design and Method(s):

In CLARIFY-MS (NCT03369665), patients with highly active relapsing MS were assigned to receive CladT 3.5 mg/kg cumulative dose over 2 years. Patients were recruited as per the EU label. Results in this interim analysis, conducted prior to the second year of treatment, were assessed using a mixed-effects linear model. Analyses were also conducted for cohorts separated by treatment naïve/prior disease-modifying therapy (DMT), and MSQoL reporting performed before/after the start of the COVID-19 pandemic, as defined as the first reported fatality within each country.

Result(s):

Of the 482 patients treated with CladT, 70.1% were female and the mean age was 37.4 years. Of the 426 patients who provided MSQoL-54 data, statistically significant (p<0.0001) improvements from Baseline to Month 12 were observed for physical and mental health composite scores with estimated changes of 4.51 (95% confidence interval [CI] 3.24–5.77) and 4.53 (95% CI 3.00–6.05), respectively. Similar trends were apparent for treatment naïve (n=121) and prior DMT (n=305) cohorts. There was no indication that the start of the COVID-19 pandemic had an impact on MSQoL-54 reporting. Regarding safety, 322 patients (66.8%) experienced at least one treatment-emergent adverse event, most commonly headache (16%), nasopharyngitis (9%), and lymphopenia (9%). The majority of observed post-baseline lymphopenia events were grade 1–2; fewer patients reported grade 3 lymphopenia, no grade 4 lymphopenia was observed.

Conclusion(s):

With only half a therapeutic dose of CladT, this interim analysis demonstrates a statistically significant improvement in the physical and mental health composite scores of MSQoL-54 at 1 year. No new safety concerns were found in this 1-year interim analysis, with no new severe or opportunistic infections that could have an impact on the established benefit:risk profile of CladT in MS.

¹Rola Alarieh, ²Aida Balegh, ³Arij Khan, ⁴Asmaa Mejally, ⁵Fatima Almaghrabi, ⁶Joelle Massouh, ⁷Omar Saleh, ⁸Ouhoud Nazmi, ⁹Qamar Bukhari, ¹⁰Richel Sulague, ¹¹Sawsan Almaymani, ¹²Waad Alsaggaf, ¹³Ahmed El Boghdady

¹King Fahad Medical City, Riyadh, Saudi Arabia; ²King Abdulaziz Hospital (KAH), Al Mahiar, Jeddah, Saudi Arabia; ³King Fahad General Hospital (KFGH), Jeddah, Saudi Arabia; ⁴King Fahad National Guard Hospital (KFNGH), Riyadh, Saudi Arabia; ⁵Heraa Hospital, Makkah, Saudi Arabia; ⁶Nehme and Therese Tohme Multiple Sclerosis Center, Beirut, Lebanon; ⁷King Fahad Specialist Hospital (KFSH), Dammam, Saudi Arabia; ⁸King Faisal Specialist Hospital and Research Center (KFSH&RC), Jeddah, Saudi Arabia; ⁹KFGH, Madinah, Saudi Arabia; ¹⁰KFSH, Riyadh, Saudi Arabia; ¹¹King Abdulaziz Medical City (KAMC), Makkah, Saudi Arabia; ¹²KAMC, Jeddah, Saudi Arabia; ¹³ Merck Serono Saudi Arabia, an affiliate of Merck KGaA Merck Group, Darmstadt, Germany.

Background/Objective(s):

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system affecting young adults. It is considered one of the major causes of disability in adults. The prevalence of MS is increasing globally. In Saudi Arabia (KSA) it is reported that the projected overall prevalence of MS is 40/100,000 for the total population and higher for Saudi nationals at 61.95/100,000 putting Saudi Arabia above the low-risk zone as per Kurtzke classification (1). With this rising prevalence, and the established significance of multidisciplinary team management, there is a growing need for specialist MS nurses. A group of specialized MS nurses formed an advisory group to support the role of the MS nurse in the management of patients with MS in KSA. This is the first advisory board meeting aiming to optimize nursing care for MS patients in KSA.

Design and Method(s):

A panel of 12 registered MS nurses representing several medical institutions across the KSA were invited to participate. The advisory board was held online on 1^st of May, 2021 and was comprised of three main topics to be discussed: “Overview of the  Roles of MS Nurse”, “MS specialized nurses (MSSN) Interventions, Challenge, and Opportunities”, and: A Patient-Centric Perspective” in MS care . Each session lasted for approximately two hours and a half hour.  Following each section, a nominal group discussion was conducted to come up with a list of challenges and opportunities that are needed to improve the role of MS nurse in KSA. 

Result(s):

 Panel members reached a consensus on the valuable role of the MS nurse in empowering patients with information regarding the course of the disease, raising awareness on adverse events of disease-modifying drugs, and providing psychological support. It was agreed that a higher level of patient education correlates with a greater need to discuss diagnostic results, relapses, disability, and disease prognosis. They commented on shortages in the required number of trained and certified nurses. They also highlighted the need to empower the role of MS nurses within the MS multidisciplinary team by increasing the number of specialized MS nurses and empowering them with the needed education and knowledge. The advisory group voted on and ranked the possible topics of interest for nurse MS education.

Conclusion(s):

MS Nurses have a vital and important role in the management of MS patient. In KSA there is a clear gap in the availability of MS nurses in general with a clear shortage of certified MS nurses. It has become essential to prepare nurses in Saudi Arabia for MS patient management using preparatory courses and seminars to support their important role in MS patient care and prepare them to get certified.

^1,2Bassem I Yamout, ³Peter Rieckmann, ⁴Diego Centonze, ⁵Gavin Giovannoni, ⁶Le H. Hua, ^7,8Celia Oreja-Guevara, ⁹Daniel Selchen, ¹⁰Per Soelberg Sørensen, ¹¹Patrick Vermersch, ¹²Heinz Wiendl, ¹³Hashem Salloukh

¹Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut, Beirut, Lebanon; ²Neurology Institute, Harley Street Medical Center, Abu Dhabi, UAE; ³Center for Clinical Neuroplasticity, Medical Park Loipl, Bischofswiesen, Department of Neurology, University of Erlangen, Germany; ⁴Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy; ⁵Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; ⁶Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA; ⁷Neurology, Hospital Clínico San Carlos, Idissc, Madrid, Spain; ⁸Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, Spain; ⁹University of Toronto, Division of Neurology, St. Michael’s Hospital, Toronto, ON, Canada; ¹⁰Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark; ¹¹Université de Lille, INSERM-U1172, Centre Hospitalier Universitaire de Lille, Fédératif Hospitalo-Universitaire Precise, Lille, France; ¹²Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany; ¹³Ares Trading SA, Eysins, Switzerland (an affiliate of Merck KGaA)

Background/Objective(s):

Gaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) during the COVID-19 pandemic, particularly relating to COVID-19 vaccination. We describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice.

Design and Method(s):

A steering committee (SC) of 10 international MS experts identified seven clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations addressing each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the SC members, voted on the recommendations. Consensus on recommendations was achieved when ≥75% of respondents expressed an agreement score of 7–9, on a 9-point scale.

Result(s):

Consensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized; the timing of vaccination around dosing of cladribine tablets (i.e., before and after a treatment course); and the safety of COVID-19 vaccination for these patients.

Conclusion(s):

There was overwhelming consensus that the risks of COVID-19 outweigh risks of vaccination in people with MS who are being treated with cladribine tablets, and all people with MS treated with cladribine tablets should be vaccinated against COVID-19 as soon as possible, unless they have a contraindication. The consensus provides timely guidance on patient selection, timing, efficacy, and safety of COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to decision-making in everyday clinical practice.

¹Asmaa Eissa, ²Tarek Menecie, ³Hoda Massoud, ²Mohammad Abboud, ²Mohammad H. Rashad

¹Nasser institute hospital for research and treatment, Cairo, Egypt; ²Alazhar University, Cairo branch, Egypt; ³Alazhar university (for girls), Cairo branch, Egypt

Introduction:

Early and appropriate treatment decision for multiple sclerosis (MS) can markedly reduce disease activity and accumulation of disability to avoid many of the long-term economic and personal expenses that result from unnecessary irreversible disability. The aim of this study is to describe switching patterns between disease modifying therapies (DMTs) in our local practice and investigate clinical characteristics that could be related to the switching process.

Material(s) and Method(s):

This is a cross-sectional study based on records of 274 MS patients who had been actively receiving available DMTs at the MS unit of Nasser Institute Hospital for Research and Treatment. The data was reviewed and collected using local database registry of the unit in the duration between the year 2016 and 2020.

The patients were classified into three groups: lateral, escalation, and multiple switch groups. The data were collected in the form of patients’ demographics, disease history, switching process data, Expanded Disability Status Scale (EDSS), and Symbol Digit Modality Test (SDMT) values.

Result(s):

A total of 274 MS patients were included in the study: 24.1% were males (n=66) and 75.9% were females (n=208). 43 patients were allocated in the lateral switch group, 178 in the escalation switch group and 53 in the multiple switch group. All baselines characteristics were balanced between the three groups except for (1) the time to switch from previous drug to the new one which was longer in the escalation and multiple switch groups compared to the lateral switch group (1.6 years versus 1.4 years versus 1.2 years, respectively; p-value=0.001), (2) the SDMT score which was significantly different between the three groups (6.5 in the multiple switch group versus 5.8 in the lateral switch group versus 5.3 in the escalation group, p-value <0.001) and (3) the mean EDSS was higher in the multiple switch group compared to the lateral and escalation switch groups (p-value <0.001). Escalation switching was the most frequent strategy of shifting between DMTs (n=178; 65%) with fingolimod being the most common drug switch to in this category. However, interferon beta 1a was the most common drug switched to in the other two groups. The most common
causes for switching DMTs was inefficacy followed by tolerability. Multiple logistic regression analysis was performed to study the association between different variables and both the escalation and multiple switch groups as compared to the lateral switch group. Education level and SDMTs were significantly associated with the escalation switching (p-value= 0.035 and p-value <0.001, respectively) while EDSS and SDMT score were significantly associated with the multiple switching strategy (p-value=0.007 and p-value=0.004, respectively).

Conclusion(s):

This cross sectional Egyptian study revealed that escalation switch was the most prominent switching pattern.The most common cause of switch was the lack of efficacy. The most common drug to be switched from was INF beta 1A sc. The most common drug to be switched to was Fingolimod and INF beta 1A sc, more in escalation group and lateral switch group respectively.

Clinical variables that were significantly associated with the escalation switching were the patient’s education, and SDMT score. The variables that were significantly associated with multiple switching were the EDSS, and SDMT score.

¹Helmut Butzkueven, ²Tim Spelman, ³Suzanne Hodgkinson, ⁴Sara Eichau Madueño, ⁴Guillermo Izquierdo, ⁵Katherine Buzzard, ⁵Olga Skibina, ¹Anneke Van Der Walt, ⁶Tomas Kalincik, ⁷François Grand-Maison

¹Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; ²MSBase Foundation, Alfred Centre, 99 Commercial Road, Melbourne, Australia; ³Liverpool Hospital, Sydney, Australia; ⁴Universitary Hospital Virgen Macarena, Seville, Spain; ⁵Box Hill Hospital, Melbourne, Australia, Melbourne, Australia; ⁶MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; ⁷Neuro Rive-Sud, Greenfield Park, Canada

Background:

Cladribine tablets are approved for relapsing multiple sclerosis (RMS) treatment in many jurisdictions. MSBase investigators are committed to characterizing real-world longitudinal treatment outcomes using this registry data. The objective of this study was to describe cladribine treatment outcomes in the MSBase cohort. These include baseline characteristics, treatment pathways, discontinuation rate, and relapse outcomes.

Material(s) and Method(s):

We extracted data from the MSBase registry for all patients with a confirmed diagnosis of MS who were newly treated with cladribine tablets. Descriptive statistics were used to analyse baseline patient characteristics recorded within 3 months prior to cladribine tablets initiation, including demographics, disease course and duration, prior disease-modifying therapies (DMT), and Expanded Disability Status Scale (EDSS). Relapse and discontinuation outcomes were described in patients with a minimum 6-month observation period.

Result(s):

As of 3^rd March 2021, a total of 782 patients, predominantly from Australia, Canada and Spain, were included. From those, 696 were relapsing-remitting MS (RRMS) patients. The median age of cladribine tablets start was 43.8 years and median disease duration was 11.8 years. Median EDSS at cladribine initiation was 2 (IQR 1.5,4). Overall, 13.3% of all RRMS patients initiated cladribine tablets as first-line therapy. Of all RRMS patients switching to cladribine tablets with a treatment gap of <6 months, the most common immediate prior DMT was fingolimod (15%), followed by natalizumab (10%) and teriflunomide (9.5%). Total follow-up time was 629 patient-years. Annualized relapse rate (ARR) on cladribine tablets was 0.11 (95% confidence interval [CI]: 0.09-0.14) compared to a 12-month pre-cladribine ARR of 0.41. Treatment persistence was 96% at 12 months (95% CI: 0.94-0.98) and 90% after 24 months (95% CI: 0.85-0.94).

Conclusion(s):

The growing MSBase real-world cladribine tablets cohort shows excellent outcomes to date. The most common switches to cladribine are from other high-efficacy DMTs such as natalizumab or fingolimod. The annualized relapse rate on treatment is 0.11, consistent with clinical trial data. The observed discontinuation rate over 24 months is very low, at 9%.

¹Rasha Mohammed Alderbi, ¹Gadah Ali Alshahrany, ¹Kholoud Ahmed Alyami, ¹Hadeil Muhanna Alsufiani, ¹Ulfat Mohammed Omar, ¹Maryam A. Al-Ghamdi, ¹Mohammad Z. Alam

¹Department of biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

Introduction:

Multiple sclerosis (MS) is an inflammatory, autoimmune disease that affects the central nervous system (CNS). One of the commonly used models to study demyelination and remyelination process involved in MS is Cuprizone (CPZ)-intoxicated mouse model. During the demyelination period, CPZ has been shown to cause impaired locomotion activity and increased anxious behavior in mice. Notably, various compounds have been known for their anti-inflammatory effect on different inflammatory and neurodegenerative diseases in-vitro and in-vivo. These include 6-Shogaol (Sh), Vanillic acid (VA) (4-hydroxy-3-methoxybenzoic acid), and Retinoic acid (RA). Since their anti-inflammatory activities could be regarded as potential treatment/co-treatment for MS disease, this study has been aimed to investigate the therapeutic effect of Sh, VA, and RA on locomotion and anxiety behavior of cuprizone-model mice.

Material(s) and Method(s):

Briefly, 6–8-week-old male SWR/J mice (15-22 g) were used (n=30) and assigned randomly into 5 groups (6 mice/group). Control group has received standard rodent chow during the entire study, while CPZ-intoxicated groups have received 0.3% CPZ-mixed chow for the first 5 weeks to induce demyelination, followed by 4 weeks of standard rodent chow for recovery. During the last 4 weeks, Sh, VA, and RA groups have received intraperitoneal injections of 25 mg/kg Sh, 30 mg/kg VA, and 20 mg/kg RA, respectively. In order to evaluate locomotion and anxiety behaviors, Open Field Test was performed using EthoVision®XT software. Total distance moved (TDM) was calculated as an indicator of locomotion, whereas percentage of time spent in the center was an indicator of anxiety. Firstly, tests were performed in 5th week of the study, where maximum demyelination was achieved, and induction of the disease was confirmed accordingly. After that, the treatment regimens have been started, and the tests were done in 7th week (two weeks after starting treatment) as it represents early spontaneous remyelination. Lastly, the tests were repeated in the 9th week by the end of remyelination progress.

Result(s):

In week 5, all CPZ-intoxicated groups showed a significant decrease in TDM and % time spent in center compared to control group, which insured the induction of the MS before starting treatment. Afterward, TDM of Sh, VA, and RA treated groups were significantly improved in week 7 compared to CPZ group. However, further decrease in % spent in the center of CPZ-intoxicated groups was shown in the same week denoting highly anxious behavior. By week 9, all treated groups exhibited a significant increase in TDM and % spent in the center compared to the CPZ group.

Conclusion(s):

In conclusion, 6-Shogaol, Vanillic acid, and Retinoic acid enhance the locomotor activity and improve anxiety behaviors in the cuprizone mouse model of Multiple sclerosis.

¹Ayesha Ashfaq

¹Sheikh Zayed Medical Complex, Lahore, Pakistan

Background:

With this study we aim to establish the importance of non radiological biomarkers of MS in establishing Prognostic value of disease activity in CIS. Monitoring disease activity in Relapsing remitting Multiple Sclerosis. Establish the value of quantification of neurofilament light chains in progressive multiple sclerosis in relation to active disease and chronic stable disease

Material(s) and Method(s):

Electronic databases search included the Cochrane and Pudmed library. 12 hits were screened from pubmed out of which 3 were selected for this study and 1 hit from Cochrane which was also selected and included in this study.

Result(s):

Prognostication in CIS: The median baseline level of serum nfl was 22.0 pg/ml (interquartile range [IQR] 11.6–40.4).

1. CIS patients subsequently developing MS had higher levels (median 30.2, iqr 16.4–48.7 pg/ml) than patients who did not develop MS (median 9.7, iqr 5.5–18.1 pg/ml, p < 0.001).
2. Median CSF nfl level in CIS patients was 731.3 (iqr 346.9–1,194.6) pg/ml and they were directly related with serum levels particularly in patients with gd-enhancing lesions .
3. Among 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at 2 years.

Relapsing remitting type:

Neurofilament light chains in CSF were:-

5 x HIGHER IN REMISSION THAN NINDS. (1896.4 ng/L, vs 365.1 ng/L).

9 x higher in relapse v/s control (3272.2 ng/L vs 364.9 ng/L).

Primary & secondary progressive types:-

Neurofilament light chains in CSF were :-

Twice more than controls (1260.4 ng/L vs 469 ng/L).

Significantly lower than in patients with relapsing remitting type. (2124.8 ng/L vs 1121.4 ng/L).

Conclusion(s):

1. Study proved that serum nfl have a prognostic value for CIS patient conversion to MS.

2. Csf neurofilament light chains correlate with disease activity throughout the course of ms, reflecting the axonal damage .

3 .Relapse is more strongly associated with elevated csf nfl than the development of progression.

4.Nfl could be the most useful marker of disease activity rather than as a marker of disability or disease stage.

^1,2,3Seraj Makkawi, ⁴Nedaa Alsulaimani, ¹Fahad A Alharbi, ⁴Reem Brashi, ⁴Renad Melebary, ⁴Shuaa Aljabri, ⁴Khalid Altowairqi, ⁴Albaraa Ashoor, ⁴Amal Alkhotani

¹College of Medicine, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; ²King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; ³Department of Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia; ⁴College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia

Background:

Multiple Sclerosis (MS) is an autoimmune disease that can be disabling to patients. Smoking has been proposed to be a risk factor for MS and to increase the risk for progression of the disease and its severity. However, it is still not clear how smoking affects MS patients regarding disease phenotype, symptoms, relapses, course, and disability. We aim to investigate the effect of smoking patients with MS patients living in Saudi Arabia.

Material(s) and Method(s):

This is an online questionnaire-based cross-sectional study. MS patients were randomly contacted through different MS societies and associations to participate in the study. The questionnaire inquired about demographics, MS phenotype and severity, and smoking status of participants. Data were collected between 30th of May 2021 and 5th of July 2021.

Result(s):

429 MS patients participated in the study. The mean age was 33.7, with a mean disease duration of 8.1 years. 61.1% of participants were female. 62.2% did not know the specific MS phenotype they have. 35.7% were current or previous smokers, with a mean smoking duration of 13.9 years. Smoking was significantly associated with the presence of multiple MS symptoms (p-value = 0.009) and their number (p-value = 0.050). In addition, there was a significant positive correlation between pack-years smoking and the number of MS symptoms with a Pearson’s r value of 0.209 (p-value < 0.05). No significant associations were found between smoking and recent relapses and disease progression, disability in terms of walking, needing a cane, or needing a wheelchair.

Conclusion(s):

Smoking was shown to have a significant effect on the number of symptoms experienced by MS patients. Higher pack-years of smoking correlate positively and significantly with a higher number of MS symptoms. Further studies to examine these relations are hence warranted.