A Rare and Challenging Presentation of Acute Hemorrhagic Leukoencephalitis With Tumefactive Demyelinating Lesions in a 41-Year-Old Male.

Acute hemorrhagic leukoencephalitis (AHLE) is a rare and severe inflammatory condition of the central nervous system (CNS), characterized by hemorrhagic lesions in the brain's white matter. Here, we present a case of AHLE with concurrent tumefactive demyelinating disease, highlighting the diagnostic and management challenges associated with this complex presentation. Tumefactive multiple sclerosis (MS) is a rare variant of MS characterized by large, space-occupying lesions in the CNS. Concurrently, hemorrhagic leukoencephalitis (HLE) represents a severe inflammatory disorder characterized by hemorrhagic lesions within the CNS white matter. The diagnosis of tumefactive MS with associated HLE posed significant diagnostic challenges due to overlapping clinical and radiological features. Management involved high-dose corticosteroid therapy and supportive care measures, with longitudinal follow-up to assess treatment response and prevent complications. The patient exhibited a favorable clinical response to treatment, with gradual improvement in symptoms and resolution of radiological abnormalities. The coexistence of tumefactive MS with HLE is exceptionally rare and presents diagnostic and therapeutic challenges. We report a 41-year-old male presenting with acute neurological symptoms, including severe headache, confusion, left-sided body weakness, slurred speech, and blurred vision. Neurological examination revealed dysarthric speech, right homonymous hemianopia, left upper motor neuron facial palsy, and motor deficits. MRI demonstrated multifocal areas of T2 hyperintensity with associated hemorrhage, suggestive of tumefactive MS with associated HLE. Diagnostic workup included neurological examination, MRI imaging, cerebrospinal fluid analysis, and serological testing. Management involved high-dose corticosteroid therapy and supportive care measures. The patient exhibited a favorable clinical response to treatment, with gradual improvement in symptoms and resolution of radiological abnormalities. Longitudinal follow-up confirmed sustained improvement. In conclusion, the coexistence of tumefactive MS with HLE poses diagnostic challenges due to overlapping features. This case underscores the importance of considering rare and atypical presentations of CNS demyelinating disease and the potential complications, including associated HLE. Comprehensive evaluation, multidisciplinary collaboration, and individualized management are essential for optimizing outcomes in patients with complex CNS inflammatory disorders.

Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

BACKGROUND AND OBJECTIVES: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

Multicentre Observational Study of Treatment Satisfaction with Cladribine Tablets in the Management of Relapsing Multiple Sclerosis in the Arabian Gulf: The CLUE Study.

INTRODUCTION: Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf. METHODS: This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent. RESULTS: Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0-82.6]), ease of use (87.4 [83.7-91.0]), tolerability (94.2 [91.0-97.3]) and effectiveness (76.2 [71.6-80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 109/L and 1.3 ± 0.3 × 109/L, respectively. CONCLUSIONS: Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment.

External validation of a clinical prediction model in multiple sclerosis.

BACKGROUND: Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS). OBJECTIVE: We aimed to validate a previously published predictive model of individual treatment response using a non-overlapping cohort from the Middle East. METHODS: We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously. RESULTS: The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%-96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%-91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%. CONCLUSION: The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.

Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Background: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. Objective: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. Methods: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. Results: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). Conclusion: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

Prevalence, severity, outcomes, and risk factors of COVID-19 in multiple sclerosis: An observational study in the Middle East.

A cross-sectional hospital records-based study was conducted to evaluate the prevalence, severity, outcomes, and identify demographic and clinical risk factors of coronavirus disease (COVID-19) in patients with MS. The study was conducted at multiple clinics in Oman, Kuwait, and the United Arab Emirates (UAE) from March 2020 to February 2021. The association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes of COVID-19 illness were evaluated using odds ratio. A total of 134 MS patients with COVID-19 (prevalence rate of 3.7%) having a median age of 35.5 years were analyzed in the study. A majority (126 [94.0%]) of patients had mild COVID-19 illness and 122 (91.0%) made a full recovery, while 1 (0.7%) patient died. The median EDSS score reported in the study was low (1.0). Univariate regression analysis showed high EDSS scores, progressive MS disease, and use of anti-CD20 therapy such as rituximab as risk factors for moderate to severe COVID-19 requiring hospitalization. Comorbidities were associated with a higher risk of non-recovery from COVID-19 in both univariate and multivariate analyses. Age, sex, smoking history, and duration of MS did not show a significant association with severity or adverse COVID-19 disease outcome. Identification of risk factors can aid in improving the treatment and monitoring of pwMS and COVID-19.

Real-world effectiveness and safety profile of teriflunomide in the management of multiple sclerosis in the Gulf Cooperation Council countries: An expert consensus narrative review.

Background: The prevalence of multiple sclerosis (MS) is increasing in Gulf Cooperation Council (GCC) countries. Multiple sclerosis contributes to significant burden on patients and caregivers. The pharmacological treatment in MS involves treating acute exacerbations and preventing relapses and disability progression using disease-modifying therapies. Clinical evidence suggests that teriflunomide is one of the therapeutic choices for patients with relapsing-remitting MS (RRMS). However, genetic and cultural differences across different regions may contribute to variations in drug use. Therefore, it is necessary to consider real-world evidence for teriflunomide usage in GCC countries. Methods: An expert group for MS gathered from GCC countries in December 2020. The consensus highlighting role of teriflunomide in MS management has been developed using clinical experiences and evidence-based approach. Results: The expert-recommended patient profile for teriflunomide usage includes individuals aged 18 years and above, both men and women (on effective contraceptives) with clinically isolated syndrome or RRMS. The factors considered were cost-effectiveness of the drug, patient preference, adherence, monitoring, established safety profile, and coronavirus disease 2019 status. Conclusion: Expert recommendations based on their clinical experience will be more helpful to clinicians in clinical settings regarding the usage of teriflunomide and provide valuable insights applicable in day-to-day practice.

MENACTRIMS practice guideline for COVID-19 vaccination in patients with multiple sclerosis.

Patients with multiple sclerosis (MS) should be vaccinated against COVID-19. All COVID-19 vaccines are effective and do not appear to carry any additional risk for patients with MS. Patients with MS should get a COVID-19 vaccine as soon as it becomes available. The risks of COVID-19 disease outweigh any potential risks from the vaccine. Even if vaccinated, patients with MS should continue to practice standard and recommended precautions against COVID-19, such as wearing a face mask, social distancing and washing hands. There is no evidence that patients with MS are at higher risk of complications from the mRNA, non-replicating viral vector, inactivated virus or protein COVID-19 vaccines, compared to the general population. COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs). The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided. For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy.

Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies.

BACKGROUND: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. METHODS: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. RESULTS: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. CONCLUSIONS: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination.

Utilization of Multiple Sclerosis Therapies in the Middle East Over a Decade: 2009-2018.

BACKGROUND: The multiple sclerosis (MS) landscape has changed over the past two decades across the world and in the Middle East. The Middle East is an ethnically diverse region located between 12° and 42° of latitude and 35° and 54° of longitude and varying altitudes. The magnitude of the shifts observed in the epidemiology and management of MS differ in each region and from country to country. OBJECTIVES: The aim of this study was to provide a clinicodemographic overview of the cohorts of patients contributed to MSBase, a large international MS registry, in the Middle East and describe disease-modifying treatment (DMT) utilization in the different countries within the region. Understanding the differences between these cohorts is integral to interpretation of the studies conducted using registry data and provides insight into clinical practice in these cohorts. METHODS: The MSBase registry was searched for patients with MS or clinically isolated syndrome from the Middle Eastern countries with data captured between 2009 and 2018. In 2-year epochs, and with special focus on the most recent epoch (2017-2018), we explored the demographic, clinical characteristics and treatment exposures of the studied cohorts and reported the results using standard descriptive statistics. RESULTS: Over the 10-year study period, 13,356 patients from 17 centers in 8 Middle Eastern countries fulfilled the inclusion criteria. The represented countries were Egypt, Iran, Kuwait, Lebanon, Oman, Saudi Arabia, Turkey and the United Arab Emirates. Overall, the represented cohort was young (median 36 years, quartiles 29-45) and captured relatively early after the onset of MS (median disease duration < 10 years, quartiles 3-12). The relapsing-remitting phenotype was the most prevalent phenotype in all countries (73-97%) and the highest proportion of progressive MS was reported in Saudi Arabia (12%). Median Expanded Disability Status Scale (EDSS) ranged from 0 to 3, depicting a mildly disabled cohort, with the exception of Saudi Arabia where the median EDSS was 4 (quartiles 1.5-6.5). The median relapse frequency was highest in Lebanon (median 1.03, 95% CI 0.94-1.16) followed by Egypt (median 1.02, 95% CI 0.89-1.24) and lowest in Saudi Arabia (median 0.70, 95% CI 0.58-0.95) and Kuwait (median 0.75, 95% CI 0.71-0.80). The treatment landscape greatly varied between different countries. Platform injectable therapies were mostly utilized in Egypt, Iran and Turkey (86%, 79% and 53%, respectively), while oral therapies and monoclonal antibodies were more commonly used in Kuwait, Lebanon and the United Arab Emirates (87.2%, 67.3% and 58.7%, respectively). CONCLUSION: Patients in the Middle East enrolled in a large multinational registry are representative of the general MS population. The spectrum of therapies used in the individual countries, however, is highly variable. Further studies that include rural and non-academic practices are needed to enhance our understanding of the MS cohorts in the Middle East.

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates.

The use of immune reconstitution therapies (IRT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a prolonged period of freedom from relapses in the absence of continuously applied therapy. Cladribine tablets is a disease-modifying treatment (DMT) indicated for highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features. Treatment with cladribine tablets is effective and well tolerated in patients with active MS disease and have a low burden of monitoring during and following treatment. In this article, an expert group of specialist neurologists involved in the care of patients with MS in the United Arab Emirates provides their consensus recommendations for the practical use of cladribine tablets according to the presenting phenotype of patients with RRMS. The IRT approach may be especially useful for patients with highly active MS insufficiently responsive to treatment with a first-line DMT, those who are likely to adhere poorly to a continuous therapeutic regimen, treatment-naïve patients with high disease activity at first presentation, or patients planning a family who are prepared to wait until at least 6 months after the end of treatment. Information available to date does not suggest an adverse interaction between cladribine tablets and COVID-19 infection. Data are unavailable at this time regarding the efficacy of COVID-19 vaccination in patients treated with cladribine tablets. Robust immunological responses to COVID-19 infection or to other vaccines have been observed in patients receiving this treatment, and treatment with cladribine tablets per se should not represent a barrier to this vaccination.

Real-world retrospective study of effectiveness and safety of FINgOlimod in relapsing remitting multiple sclerosis in the Middle East and North Africa (FINOMENA).

OBJECTIVES: Evidence on the effectiveness and safety of fingolimod in real-world clinical practice in the Middle East and North African (MENA) region is limited. This study aimed to evaluate the effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) in real-world setting in the MENA region. PATIENTS AND METHODS: RRMS patients who had been treated with fingolimod for at least 12 months were retrospectively identified from the databases of 34 centers across the MENA region. Study outcomes included the annualized relapse rate (ARR), relapse-free rate (RFR), time to first and second relapses, mean change in Expanded Disability Status Scale (EDSS), proportion of patients with Magnetic Resonance Imaging (MRI) activity and no evidence of disease activity (NEDA)-3, retention of patients on treatment, as well as all safety measures. RESULTS: A total of 806 patients were included: 66.34 % female; mean age 32.97 ± 9.62 years; mean disease duration 4.92 ± 4.66 years; mean fingolimod use 37.2 ± 16.7 months. Most patients had received previous disease-modifying therapy (79.65 %). Compared to the year preceding fingolimod initiation, RFR improved (33.00%-86.35%; p < 0.001), ARR decreased (0.84 ± 0.73 to 0.16 ± 0.45; p = 0.005), EDSS decreased (2.69 ± 1.74-2.01 ± 1.66; p < 0.001), and the proportion of patients with Gadolinium-enhancing T1 lesions decreased (57.84 % to 12.93 %; p < 0.001), after 12 months of fingolimod treatment. NEDA-3 was achieved in 41.3 % of patients. Median time to first and second relapses was not reached since 86.35 % and 98.39 % of patients had not experienced relapses for the first time and second time, respectively. Eight-hundred one (99.38 %) patients continued fingolimod treatment beyond 12 months. One-hundred thirty patients (16.13 %) experienced adverse events, mainly lymphopenia (5.46 %) and leukopenia (2.11 %), while 13 patients (1.61 %) experienced serious adverse events. CONCLUSION: This study confirms the effectiveness and safety profile of fingolimod in real-world setting in the Middle East and North African (MENA) region.

The use of alemtuzumab in patients with relapsing-remitting multiple sclerosis: the Gulf perspective.

Over the past decade, the development of high-efficacy disease-modifying therapies (DMTs) has been responsible for more effective management of relapsing-remitting multiple sclerosis (RRMS). However, the gaps in optimal care for this complex disease remain. Alemtuzumab (Lemtrada®) is a highly efficacious DMT that shows better patient outcomes and therapeutic benefits, but its use is under-recognized in the Gulf region. Experts in the care of multiple sclerosis shared their opinions based on study data and daily clinical experience in identifying the appropriate patient profile suitable for alemtuzumab's therapeutic benefits. Age, disease activity and severity, disability status, physician experience, and economic condition are some of the key indicators for alemtuzumab use.

Disease-Modifying Drugs and Family Planning in People with Multiple Sclerosis: A Consensus Narrative Review from the Gulf Region.

Most disease-modifying drugs (DMDs) are contraindicated in pregnancy. Management of MS is especially challenging for pregnant patients, as withdrawal of DMDs leave the patient at risk of increased disease activity. We, a group of experts in MS care from countries in the Arab Gulf, present our consensus recommendations on the management of MS in these patients. Where possible, a patient planning pregnancy can be switched to a DMD considered safe in this setting. Interferon ß now can be used during pregnancy, where there is a clinical need to maintain treatment, in addition to glatiramer acetate. Natalizumab (usually to 30 weeks' gestation for patients with high disease activity at high risk of relapse and disability progression) may also be continued into pregnancy. Cladribine tablets and alemtuzumab have been hypothesised to act as immune reconstitution therapies (IRTs). These drugs provide a period of prolonged freedom from relapses for many patients, but the patient must be prepared to wait for up to 20 months from initiation of therapy before becoming pregnant. If a patient becomes pregnant while taking fingolimod, and requires continued DMD treatment, a switch to interferon ß or natalizumab after a variable washout period may be prescribed, depending on the level of disease activity. Women who wish to breastfeed should be encouraged to do so, and interferon ß may also be used during breastfeeding. There is a lack of data regarding the safety of using other DMDs during breastfeeding.

High-efficacy therapies for relapsing-remitting multiple sclerosis: implications for adherence. An expert opinion from the United Arab Emirates.

The number of disease-modifying treatments (DMDs) for relapsing-remitting multiple sclerosis has increased. DMDs differ not only in their efficacy and safety/tolerability, but also in the treatment burden of, associated with their initiation, route/frequency of administration, maintenance treatment and monitoring. High-efficacy DMDs bring the prospect of improved suppression of relapses and progression of disability, but may have serious safety issues, and burdensome long-term monitoring. Studies of patient preferences in this area have focused on side effects, efficacy and route of administration. Adherence to DMDs is often suboptimal in relapsing-remitting multiple sclerosis and there is a need to understand more about how the complex therapeutic and administration profiles of newer DMDs interact with these barriers to support optimal adherence to therapy.

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review.

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era.

Neuromyelitis optica spectrum disorders in Arabian Gulf (NMOAG); establishment and initial characterization of a patient registry.

OBJECTIVE: To describe the clinical and radiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) patients from the Arabian Gulf relative to anti-aquaporin 4 antibody serostatus. METHODS: Retrospective multicentre study of hospital records of patients diagnosed with NMOSD based on 2015 International Panel on NMOSD Diagnosis (IPND) consensus criteria. RESULTS: One hundred forty four patients were evaluated, 64.3% were anti-AQP4 antibody positive. Mean age at onset and disease duration were 31±12 and 7 ±â€¯6 years respectively. Patients were predominantly female (4.7:1). Overall; relapsing course (80%) was more common than monophasic (20%). Optic neuritis was the most frequent presentation (48.6%), regardless of serostatus. The proportion of patients (54.3%) with visual acuity of ≤ 0.1 was higher in the seropositive group (p = 0.018). Primary presenting symptoms of transverse myelitis (TM) were observed in 29% of patients, and were the most significant correlate of hospitalization (p<0.001). Relative to anti-APQ4 serostatus, there were no significant differences in terms of age of onset, course, relapse rates or efficacy outcomes except for oligoclonal bands (OCB), which were more often present in seronegative patients (40% vs.22.5%; p = 0.054). Irrespective of serostatus, several disease modifying therapies were instituted including steroids or immunosuppressives, mostly, rituximab and azathioprine in the cohort irrespective of serostatus. The use of rituximab resulted in reduction in disease activity. CONCLUSION: This is the first descriptive NMOSD cohort in the Arabian Gulf region. Seropositive patients were more prevalent with female predominance. Relapsing course was more common than monophasic. However, anti-AQP4 serostatus did not impact disease duration, relapse rate or therapeutic effectiveness. These findings offer new insights into natural history of NMOSD in patients of the Arabian Gulf and allow comparison with patient populations in different World regions.

Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity.

Recent research has expanded our understanding of the natural history and clinical course of multiple sclerosis (MS) in the Arabian Gulf region. In addition, the number of available therapies for MS has increased greatly in recent years, which complicates considerably the design of therapeutic regimens. We, an expert group of physicians practising in Arabian Gulf countries, present pragmatic consensus recommendations for the use of disease-modifying therapy, according to the level of MS disease activity, according to objective criteria, and prior treatment (if any) received by a given patient.