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Introduction: B cell depletion has been established as an efficacious anti-inflammatory therapy in people with relapsing forms of multiple sclerosis (MS). Ublituximab (ublituximab-xiiy) is the latest approved chimeric glycoengineered anti-CD20 monoclonal antibody (mAb) for the treatment of relapsing forms of MS., Areas Covered: In this narrative review, the authors explore the safety and effectiveness of data derived from the Phase 2 and Phase 3 ublituximab trials and from their respective post-hoc analyses. Moreover, they consider the similarities and differences between the currently available anti-CD20 antibodies for treatment of relapsing MS. Lastly, the authors discuss the role and place of ublituximab in the current disease modifying therapy landscape., Expert Opinion: Ublituximab is a rapid-acting and effective anti-inflammatory option as a treatment in people with relapsing MS that significantly reduced the annualized relapse rate and MRI-based disease activity. When compared to the Phase III trials of the other two anti-CD20 mAbs (ocrelizumab and ofatumumab), ublituximab did not result with reduction of 3 or 6-month confirmed disability progression. These differences may be attributed to the overall low rate of progression in both the ublituximab and the active comparator teriflunomide arm. Future data from open-label extensions are warranted. There was no significant reduction of ublituximab on whole-brain atrophy compared to teriflunomide.

Introduction : The successful development of anti-inflammatory disease-modifying treatments (DMT) significantly improved disease outcomes and longevity of persons with multiple sclerosis (pwMS). However, the shift toward an elderly MS population has resulted with new concerns regarding DMT efficacy and safety. Areas covered : This review summarizes the evidence of an age-based decrease in the efficacy of MS DMTs and increase in pharmacovigilance concerns. The age effects on pathophysiological MS processes, immunosenescence and its relevance to DMT selection or discontinuation are also reviewed. Lastly, the authors discuss the influence of age-associated comorbidities on DMT initiation and drug-induced events. Expert opinion : There is an age discrepancy between pwMS included in regulatory drug trials and an aging real-world MS population. Most trials demonstrate significantly diminished anti-inflammatory efficacy in patients older than 40 years old. Older age is associated with a greater risk for adverse events including serious infections. Age-associated comorbidities influence the risk-benefit analysis and sometimes cause patients to discontinue DMTs. Instead of chronological age cutoffs, therefore, studies should aim at promoting biologically-based age biomarkers.

Introduction: Conventional imaging measures remain a key clinical tool for the diagnosis multiple sclerosis (MS) and monitoring of patients. However, most measures used in the clinic show unsatisfactory performance in predicting disease progression and conversion to secondary progressive MS., Areas Covered: Sophisticated imaging techniques have facilitated the identification of imaging biomarkers associated with disease progression, such as global and regional brain volume measures, and with conversion to secondary progressive MS, such as leptomeningeal contrast enhancement and chronic inflammation. The relevance of emerging imaging approaches partially overcoming intrinsic limitations of traditional techniques is also discussed., Expert Opinion: Imaging biomarkers capable of detecting tissue damage early on in the disease, with the potential to be applied in multicenter trials and at an individual level in clinical settings, are strongly needed. Several measures have been proposed, which exploit advanced imaging acquisitions and/or incorporate sophisticated post-processing, can quantify irreversible tissue damage. The progressively wider use of high-strength field MRI and the development of more advanced imaging techniques will help capture the missing pieces of the MS puzzle. The ability to more reliably identify those at risk for disability progression will allow for earlier intervention with the aim to favorably alter the disease course.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. Over the last two decades, more favorable MS long-term outcomes have contributed toward increase in prevalence of the aged MS population. Emergence of age-associated pathology, such as cardiovascular diseases, may interact with the MS pathophysiology and further contribute to disease progression. Areas covered: This review summarizes the cardiovascular involvement in MS pathology, its disease activity, and progression. The cardiovascular health, the presence of various cardiovascular diseases, and their effect on MS cognitive performance are further explored. In similar fashion, the emerging evidence of a higher incidence of extracranial arterial pathology and its association with brain MS pathology are discussed. Finally, the authors outline the methodologies behind specific perfusion magnetic resonance imaging (MRI) and ultrasound Doppler techniques, which allow measurement of disease-specific and age-specific vascular changes in the aging population and MS patients. Expert opinion: Cardiovascular pathology significantly contributes to worse clinical and MRI-derived disease outcomes in MS. Global and regional cerebral hypoperfusion may be associated with poorer physical and cognitive performance. Prevention, improved detection, and treatment of the cardiovascular-based pathology may improve the overall long-term health of MS patients.

Introduction: Brain atrophy measurement in multiple sclerosis (MS) has become an important outcome for determining patients at risk for developing physical and cognitive disability., Areas Covered: In this article, we discuss the methodological issues related to using this MRI metric routinely, in a clinical setting. Understanding trajectories of annualized whole brain, gray and white matter, thalamic volume loss, and enlargement of ventricular space in specific MS phenotypes is becoming increasingly important. Evidence is mounting that disease-modifying treatments exert a positive effect on slowing brain atrophy progression in MS. Expert Commentary: While there is a need to translate measurement of brain atrophy to clinical routine at the individual patient level, there are still a number of challenges to be met before this can actually happen, including how to account for biological confounding factors and pseudoatrophy, standardize acquisition and analyses parameters, which can influence the accuracy of the assessments.