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

Abstract 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

Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD.

ObjectiveTo define the frequency, duration, and severity of intractable nausea, vomiting, or hiccups in aquaporin-4-immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and propose diagnostic criteria and a severity scale for area postrema syndrome (APS).MethodsAn International NMOSD database was interrogated for frequency of APS. Patients with AQP4-IgG-positive NMOSD completed an APS symptom questionnaire. Nausea and vomiting severity was derived from the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score. The diagnostic criteria, severity scale, and immunotherapy response was applied to a prospective validation cohort of patients from multiple centers.ResultsAnalysis of an international database for AQP4-IgG-seropositive NMOSD (n = 430) revealed a high prevalence of isolated APS attacks (onset 7.1%-10.3%; subsequent 9.4%-14.5%) across continents. For 100 patients with 157 episodes of APS, nausea (n = 127, 81%) lasted for a median of 14 days (range 2-365), vomiting (113, 72%) with a median of 5 episodes/d (2-40) lasted 1-20 minutes, and hiccups (102, 65%) lasted a median of 14 days (2-365). Symptoms consistently and completely resolved following immunotherapy. Data were used to propose APS diagnostic criteria and repurpose PUQE score (hiccups severity grade based on symptom duration). The clinical utility was demonstrated in a prospective validation cohort.ConclusionIsolated APS attacks are frequently encountered both at onset and during the NMOSD course. The diagnostic criteria proposed here will assist clinicians in recognizing APS. Diagnosis of an APS attack earlier than 48 hours is possible if a dorsal medulla lesion is detected. Accurate diagnosis and evaluation of APS attack severity will assist in outcome measurement in NMOSD clinical trials

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Family Planning within the Management of MS

This review article addresses the complex issues faced by individuals with Multiple Sclerosis (MS) who are planning a family, becoming pregnant, or wishing to breastfeed their baby. Recommendations and guidelines were discussed and agreed upon by neurologists, neuroradiologists, nurses, and pharmacists involved in the management of MS in the Kingdom of Saudi Arabia (KSA). MS itself does not harm a pregnancy, and people with MS of childbearing age can be encouraged to enjoy family life. Family planning should be a part of the initial conversation with a newly diagnosed patient of childbearing age. Interferons and glatiramer acetate can be continued throughout pregnancy and can be administered during breastfeeding if the benefits outweigh the risks. These DMTs may be considered for a woman with well-controlled MS who is planning a pregnancy or otherwise not using contraception, according to an individualized risk-benefit analysis. The use of contraception should be maintained during the administration of other disease-modifying therapies (DMTs). Natalizumab can be administered at a reduced administration frequency to women with high MS disease activity up to 30 weeks gestation (this agent may induce hematological abnormalities in the fetus). Other DMTs should be withdrawn for variable periods before contraception is stopped and immediately after the discovery of a pregnancy (beware of rebound disease activity after withdrawing natalizumab or fingolimod). Resumption of treatment should not be delayed in women at risk of relapse during the postpartum period and especially in those who do not wish to breastfeed

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Symptom Management and Vaccination

This article deals with recommendations on the management of symptoms of MS and on the provision of vaccinations in patients receiving disease-modifying therapies (DMTs). Symptoms of MS, such as fatigue, depression, urinary symptoms, spasticity, impairment of gait, and sexual dysfunction, are common in this population. Recognizing and addressing these symptoms is key to maintaining the quality of life of people with MS. Vaccination status should be reviewed and updated prior to initiation of DMTs. In general, vaccination should be avoided for variable periods after the initiation of some DMTs. Live attenuated vaccines are contraindicated and should be considered on a case-by-case basis. These consensus recommendations will present the best practices for vaccination in Saudi Arabia before, during, and after the COVID-19 pandemic. The recommendations will be updated periodically and as needed as new evidence becomes available

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Disease-Modifying Therapies and Management of Relapses

For the past 10 years, disease-modifying therapy (DMT) options for multiple sclerosis (MS) have grown remarkably where DMTs have been shown to reduce the risk of MS relapses. MS patients are advised to begin treatment with a DMT shortly after diagnosis to limit the possibility of disease progression over time. While patients with radiologically isolated syndrome do not require pharmacologic treatment, high-risk patients with clinically isolated syndrome are advised to start DMTs. This article provides evidence-based recommendations for DMT use in MS management, helping healthcare practitioners advise patients on treatment decisions. We aim to provide recommendations for the management of acute MS relapses. The recommendations herein were developed following the gathering of a panel of experts after evaluating international guidelines, and the latest evidence was collected through a comprehensive literature review

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Disease-Modifying Therapies and Management of Relapses

For the past 10 years, disease-modifying therapy (DMT) options for multiple sclerosis (MS) have grown remarkably where DMTs have been shown to reduce the risk of MS relapses. MS patients are advised to begin treatment with a DMT shortly after diagnosis to limit the possibility of disease progression over time. While patients with radiologically isolated syndrome do not require pharmacologic treatment, high-risk patients with clinically isolated syndrome are advised to start DMTs. This article provides evidence-based recommendations for DMT use in MS management, helping healthcare practitioners advise patients on treatment decisions. We aim to provide recommendations for the management of acute MS relapses. The recommendations herein were developed following the gathering of a panel of experts after evaluating international guidelines, and the latest evidence was collected through a comprehensive literature review

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

Objective To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD