Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

A retrospective claims analysis of fatigue in patients with multiple sclerosis on disease-modifying therapy.

Background: Fatigue, one of the most common symptoms in patients with multiple sclerosis (MS), severely impairs quality of life and the ability to work or perform activities of daily living. Real-world data on fatigue in MS can help inform healthcare decisions and identify care gaps. We identified fatigue in patients with MS, using existing codes for fatigue and proxies of fatigue in healthcare claims database records and characterized cohorts with and without markers of fatigue who had been prescribed disease-modifying therapies for MS (MS-DMTs).

Revealing the immune cell subtype reconstitution profile in patients from the CLARITY study using deconvolution algorithms after cladribine tablets treatment.

Immune Cell Deconvolution methods utilizing gene expression profiling to quantify immune cells in tissues and blood are an appealing alternative to flow cytometry. Our objective was to investigate the applicability of deconvolution approaches in clinical trial settings to better investigate the mode of action of drugs for autoimmune diseases. Popular deconvolution methods CIBERSORT and xCell were validated using gene expression from the publicly available GSE93777 dataset that has comprehensive matching flow cytometry.

T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy.

Background: Multiple sclerosis (MS) is a neurological disorder marked by accumulating immune-mediated damage to the central nervous system. The dysregulated immune system in MS combined with immune effects of disease-modifying therapies (DMTs) used in MS treatment could alter responses to infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Most of the literature on immune response to SARS-CoV-2 infection and COVID-19 vaccination, in both the general population and patients with MS on DMTs, has focused on humoral immunity.

Multiple sclerosis: relationship between locus of control and quality of life in persons with low versus high disability.

Health Locus of Control (HLOC) is the degree to which individuals believe that their health outcomes are controlled by 'external' factors - environmental forces, chance, fate, other people, or some higher power - or by 'internal' factors - their own behavior or action. Most of the literature on HLOC associates an Internal Health Locus of Control (IHLOC) to pro-health behaviors and better health outcomes. However, a few studies also suggest that in chronic illnesses, an External Health Locus of Control (EHLOC) could be beneficial with respect to pro-health behaviors and perceptions of Quality of Life (QoL), challenging assumptions about what leads to the most effective psychological coping in the face of difficult circumstances.

Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary.

People with multiple sclerosis (also shortened to MS) may have difficulties staying on treatment due to side effects. Cladribine tablets, approved for treating relapsing forms of MS, are given by mouth for four short periods over two years. The benefit of convenient dosing may be lost if side effects prevent people with MS from finishing their treatment.

Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets.

Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or >50 years) on lymphopenia following CladT 3.

Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial.

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT).

Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs.

Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled.

N-acetyl cysteine administration affects cerebral blood flow as measured by arterial spin labeling MRI in patients with multiple sclerosis.

Background: The purpose of this study was to explore if administration of N-acetyl-cysteine (NAC) in patients with multiple sclerosis (MS) resulted in altered cerebral blood flow (CBF) based on Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI).

Methods: Twenty-three patients with mild to moderate MS, (17 relapsing remitting and 6 primary progressive) were randomized to either NAC plus standard of care (N = 11), or standard of care only (N = 12). The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500mg 2x/day) the other six days.

Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis.

Background: Treatment-emergent adverse events (TEAEs) that occur close to treatment initiation may negatively affect overall tolerability and adherence. It is important to develop a clear understanding of potential early TEAEs after initiating treatment with cladribine tablets.

Objective: To identify TEAEs that begin early in the course of treatment in patients enrolled in CLARITY and ORACLE-MS studies.

Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study.

Background: In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE).

Challenges in multiple sclerosis care: Results from an international mixed-methods study.

Background: Disease-modifying treatment (DMT) selection for people with multiple sclerosis (MS) is challenging. Neurologists and advanced practice nurses (APNs) in MS care may be facing knowledge and confidence gaps when screening patients to initiate or switch between DMTs, assessing the safety of new DMTs and monitoring for adverse events. Healthcare providers are required to demonstrate enhanced patient communication skills, to share treatment decisions and assess treatment adherence.

Subgroup analysis of clinical and MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study.

Background: In the Phase 3, 96-week ORACLE-MS study, cladribine 10 mg tablets (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly reduced the rate of conversion to clinically definite multiple sclerosis (CDMS) per the Poser criteria (henceforth referred to as CDMS), multiple sclerosis (MS) per the 2005 McDonald criteria, and the number of new or persisting T1 gadolinium-enhancing (Gd+), new or enlarging T2, and combined unique active (CUA) lesions versus placebo in participants with a first clinical demyelinating event (FCDE).

Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety.

Introduction: Although use of contraception was pre-specified during cladribine clinical trials for multiple sclerosis, some pregnancies did occur.

Objective: This analysis reports on pregnancy outcomes in the cladribine clinical development program.

Methods: Pregnancy outcomes in female patients (direct pregnancies) and those arising from partner pregnancies (i.

N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study.

Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS).

The Relationship Between Multiple Sclerosis Symptom Severity Measures and Performance on Driving Variability Metrics in a Virtual Reality Simulator.

Objective: Driving ability can be compromised in individuals with multiple sclerosis (MS); however, the progressive nature of multiple sclerosis makes it difficult for clinicians to assess when performance on functional tasks, such as driving, has started to decline. The aim of the study was to evaluate the relationship between two measures of multiple sclerosis severity, the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite, and minor driving errors in a virtual reality driving simulator.

Design: Symptom severity was measured in 31 active drivers with multiple sclerosis using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite.

Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers.

Background: Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and CLARITY Extension).

Development and Validation of the FSIQ-RMS: A New Patient-Reported Questionnaire to Assess Symptoms and Impacts of Fatigue in Relapsing Multiple Sclerosis.

Objectives: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format.

Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised.

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis.

Background: Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously.

Objective: Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets.