Unmet Needs and Treatment of Relapsing-Remitting Multiple Sclerosis in Saudi Arabia: Focus on the Role of Ofatumumab.

Treatment-pattern data suggest that some patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) may not be receiving optimal treatment. A virtual meeting of ten expert Saudi neurologists, held on October 23, 2020, discussed unmet needs in relapsing-remitting MS (RRMS), and the role of ofatumumab as a suitable treatment in the KSA. Multiple unmet needs were identified: poor quality of life, with high rates of depression and anxiety; a negative impact of MS on work ability; treatment choices that may compromise efficacy for safety or vice versa; inconvenient or complex dosage regimens; and limited access to patient education and support. Early use of highly effective disease-modifying treatments (DMTs) results in better patient outcomes than starting with less effective treatments and downstream escalation, but this strategy may be underutilized in the KSA. B cells are important in MS pathogenesis, and treatments targeting these may improve clinical outcomes. Ofatumumab differs from other B cell-depleting therapies, being a fully human monoclonal antibody that binds to CD20 at a completely separate site from the epitope bound by ocrelizumab, and being administered by subcutaneous injection. When compared with teriflunomide in two randomized, phase 3 clinical trials in patients with RRMS, ofatumumab was associated with significant reductions in annualized relapse rates, rates of confirmed disability worsening, and active lesions on magnetic resonance imaging. The incidence of adverse events, including serious infections, was similar with the two treatments. Ofatumumab is a valuable first- or second-line treatment option for RRMS in the KSA, particularly for patients who would benefit from highly effective DMTs early in the disease course, and for those who prefer the convenience of self-injection. Future research will clarify the position of ofatumumab in RRMS treatment, and comparative cost data may support the broad inclusion of ofatumumab in formularies across the KSA.

Stroke Incidence and Outcome in a Population With COVID-19.

Background and Purpose: COVID-19 is associated with systemic thromboembolism including stroke. The study evaluated the 30-days stroke incidence in SARS-CoV-2 PCR positive patients and described the outcome of such patients. Methods: This is a retrospective study of consecutive patients with a positive SARS-CoV-2 PCR test between March 1st, 2020 and August 30th, 2020. The study included COVID-19 patients who were hospitalized and had a stroke within 30 days from the positive PCR test. Results: During the study period, there were 4301 patients with a positive SARS-CoV-2 PCR test. Of those, 1786 patients (41.5%) were hospitalized and 4 patients developed a stroke within 30 days. The 30-days stroke incidence was 0.09% and 0.2% of all and hospitalized patients, respectively. The mean age of stroke patients was 78 years and 2 died during the same hospitalization. The 4 patients had comorbidities, one had pre-existing atrial fibrillation and all had ischemic stroke. Conclusion: This study showed a low 30-day incidence of stroke among COVID-19 patients.

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.

Prevalence of Pediatric Onset Multiple Sclerosis in Saudi Arabia.

BACKGROUND: The prevalence of multiple sclerosis (MS) appears to be increasing worldwide. However, data on the pediatric onset of MS is lacking, particularly in developing countries. OBJECTIVE: This study is aimed at reporting the current burden of the pediatric onset of MS in the five regions of Saudi Arabia. METHODS: This study used relevant data from the National Saudi MS Registry that was operational between 2015 and 2018. The data on patients with pediatric onset MS from all the hospitals included in the registry was retrospectively analyzed using the age of diagnosis. Patients who were 1-18 years old when diagnosed were included in the analysis. RESULTS: The registry included 287 patients with pediatric onset MS, with a mean age of diagnosis at 15.7 (SD: 2.06). 74.2% of the participants were females. For the included hospitals, the estimated prevalence of pediatric MS was at 2.73/100,000 pediatric Saudi population. The prevalence of pediatric MS in the remaining nonparticipant hospitals was then projected taking into account both the size of pediatric population in the Kingdom per region and the number of facilities treating and managing MS in each of the corresponding regions. The overall projected prevalence was found to be 14.33/100,000 Saudi pediatric population. CONCLUSION: To the best of our knowledge, this study reported the latest epidemiological data of pediatric onset of MS in Saudi Arabia. The current prevalence of MS among the pediatric Saudi population was found to be 2.73/100,000, and the overall projected prevalence was estimated at 14.33/100,000. Our findings were similar to those in other pediatric MS cohorts. Further studies are needed to understand the long-term prognosis, response to treatment, and disease course.

Registry of patients with multiple sclerosis and COVID-19 infection in Saudi Arabia.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread and developed as a pandemic threatening global health. Patients with multiple sclerosis (MS)-an autoimmune demyelinating inflammatory disease of the central nervous system (CNS)-are predominantly treated with immunomodulatory/immunosuppressive disease-modifying therapies (DMTs), which can increase the risk of infection. Therefore, there is concern that these patients may have a higher risk of COVID-19. In response to growing concerns of neurologists and patients, this study aimed to determine the prevalence, severity, and possible complications of COVID-19 infection in patients with MS in Saudi Arabia (SA). METHODS: In this prospective cohort study, demographic and clinical data were obtained from patients residing in SA with MS who had a positive result for COVID-19 per reverse transcription-polymerase chain reaction test or viral gene sequencing, using respiratory or plasma samples. Comparison of COVID-19 severity groups was performed using one-way ANOVA or Kruskal-Wallis test for numerical variables and Chi-squared test for categorical variables. RESULTS: Seventy patients with MS and COVID-19 (71% female) were included in this analysis. Of the 53 (75.7%) patients receiving a DMT at the time of COVID-19 infection, the most frequently used DMTs were fingolimod (25%) and interferon-beta (25%). Nine (13%) patients had MS relapse and were treated with intravenous methylprednisolone in the four weeks before COVID-19 infection. The most common symptoms at the peak of COVID-19 infection were fever (46%), fatigue (37%), and headache (36%). Symptoms lasted for a mean duration of 8.7 days; all symptomatic patients recovered and no deaths were reported. COVID-19 severity was categorized in three groups: asymptomatic (n = 12), mild-not requiring hospitalization (n = 48), and requiring hospitalization (n = 10; two of whom were admitted to the intensive care unit [ICU]). Between the three groups, comparison of age, body mass index , Expanded Disability Severity Score , MS disease duration, and DMT use at the time of infection showed no significant differences. A higher percentage of patients who were admitted to hospital or the ICU (40%; p = 0.026) presented with an MS relapse within the prior four weeks compared with those who were asymptomatic or had a mild infection (both 8.3%). CONCLUSION: These findings present a reassuring picture regarding COVID-19 infection in patients with MS. However, patients with MS who have had a relapse in the preceding four weeks (requiring glucocorticoid treatment) may have an increased risk of severe COVID-19.

Managing multiple sclerosis in the Covid19 era: a review of the literature and consensus report from a panel of experts in Saudi Arabia.

Disease-modifying therapies (DMT) for relapsing-remitting MS (RRMS) act on the immune system, suggesting a need for caution during the SARS-CoV2/Covid-19 pandemic. A group of experts in MS care from Saudi Arabia convened to consider the impact of Covid-19 on MS care in that country, and to develop consensus recommendations on the current application of DMT therapy. Covid-19 has led to disruption to the care of MS in Saudi Arabia as elsewhere. The Expert Panel considered a DMT's overall tolerability/safety profile to be the most important consideration on whether or not to prescribe at this time. Treatment can be started or continued with interferon beta, teriflunomide, dimethyl fumarate, or natalizumab, as these DMTs are not associated with increased risk of infection (there was no consensus on the initiation of other DMTs). A consensus also supported continuing treatment regimens with fingolimod (or siponimod) and cladribine tablets for a patient without active Covid-19. No DMT should be imitated in a patient with active Covid-19, and (only) interferon beta could be continued in the case of Covid-19 infection. Vaccination against Covid-19 is a therapeutic priority for people with MS. New treatment should be delayed for 2-4 weeks for vaccination. Where treatment is already ongoing, vaccination against Covid-19 should be administered immediately without disruption of treatment (first-line DMTs, natalizumab, fingolimod), when lymphocytes have recovered sufficiently (cladribine tablets, alemtuzumab) or 4 months after the last dose (ocrelizumab). These recommendations will need to be refined and updated as new clinical evidence in this area emerges.

Familial aggregation of multiple sclerosis: Results from the national registry of the disease in Saudi Arabia.

BACKGROUND: Multiple Sclerosis (MS) is a chronic CNS inflammatory disease commonly affecting young adults. Both genetics and environmental factors have been reported to have a role in pathophysiology of the disease. OBJECTIVE: This article aims to report familial nature and aspects of MS in Saudi Arabia. METHOD: The study utilized data collected by the National Saudi MS Registry between 2015 and 2018; especially data relevant to the familial history of MS. SPSS 22 was used for all analysis and reporting. Statistical significance was set at p-value < 0.05. RESULTS: The registry included 20 hospitals and a total of 2516 patients from the different regions of Saudi Arabia with median age 32.00 (Range: 11-63) and 66.5% being female. About 12.8% of all registered patients reported a family history of MS (95%CI: 11.2-13.9). Reported parental consanguinity was significantly higher among patients with family history (FMS) (56.3%) compared to non-FMS patients (27.9%). 42.53% of FMS patients reported having siblings affected with MS (95%CI: 37.01-48.21), with more female siblings affected than males (63.4% vs 36.6% respectively). CONCLUSION: Our Findings suggested that FMS was less prevalent than what was reported previously; however, parental consanguinity was significantly more prevalent among FMS patients than non-FMS. Our findings were in line with those reported in recent studies in the region, but lower than those reported by western countries indicating that increasing prevalence of MS in Saudi Arabia could be multifactorial and other environmental factors should be considered for understanding this recent rise in the prevalence of MS in Saudi Arabia.

Cladribine Tablets and Relapsing-Remitting Multiple Sclerosis: A Pragmatic, Narrative Review of What Physicians Need to Know.

Immune reconstitution therapy (IRT) is an emerging management concept for multiple sclerosis, whereby a short course of treatment provides long-lasting suppression of disease activity. "Cladribine tablets 10 mg" refers to a total cumulative dose of cladribine given over 2 years (henceforth referred to as cladribine tablets 3.5 mg/kg); it is a relatively new treatment option that is hypothesised to act as an IRT acting preferentially on the adaptive immune system. A randomised, 2-year, placebo-controlled trial (CLARITY) showed that treatment with cladribine tablets reduced indices of disease activity (relapses, lesions on magnetic resonance images, disability progression) and that this effect outlasted the pharmacologic effect of the treatment on the immune system (mainly a reduction in circulating B and T cells, with little effect on components of the innate immune system such as monocytes). CLARITY Extension, a 2-year extension to this trial, demonstrated durable efficacy, also in patients who received the standard 2-year course of cladribine tablets 3.5 mg/kg and were re-randomised to placebo for a further 2 years. Relative risk reductions for relapse rate with cladribine tablets 3.5 mg/kg were similar for patients with or without prior high disease activity. Reductions in disability progression with cladribine tablets 3.5 mg/kg were higher in patients with prior high relapse rates with or without prior treatment non-response. In this review, we describe the therapeutic profile of cladribine tablets 3.5 mg/kg and provide practical information on initiating this treatment option in the most appropriate patients.

A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia.

As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia.