Klaus Schmierer1,2, Per S Sørensen3,4, David Baker1. 1. The Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London. 2. Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK. 3. Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet. 4. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Abstract
PURPOSE OF REVIEW: Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy. RECENT FINDINGS: With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy. SUMMARY: The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.
PURPOSE OF REVIEW: Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy. RECENT FINDINGS: With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy. SUMMARY: The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.
Authors: Kimberley Allen-Philbey; Stefania De Trane; Zhifeng Mao; Cesar Álvarez-González; Joela Mathews; Amy MacDougall; Andrea Stennett; Xia Zhou; Ozlem Yildiz; Ashok Adams; Lucia Bianchi; Camilla Blain; Christine Chapman; Karen Chung; Cris S Constantinescu; Catherine Dalton; Rachel A Farrell; Leonora Fisniku; Helen Ford; Bruno Gran; Jeremy Hobart; Zhaleh Khaleeli; Miriam Mattoscio; Sue Pavitt; Owen Pearson; Luca Peruzzotti-Jametti; Antonio Scalfari; Basil Sharrack; Eli Silber; Emma C Tallantyre; Stewart Webb; Benjamin P Turner; Monica Marta; Sharmilee Gnanapavan; Gunnar Juliusson; Gavin Giovannoni; David Baker; Klaus Schmierer Journal: Ther Adv Neurol Disord Date: 2021-11-25 Impact factor: 6.570