MULTIPLE SCLEROSIS: Edited by Giancarlo ComiThe window of opportunity for treatment of progressive multiple sclerosisSorensen, Per Soelberga; Fox, Robert J.b; Comi, GiancarlocAuthor Information aDepartment of Neurology, Danish Multiple Sclerosis Center, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark bMellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA cInstitute of Experimental Neurology, San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy Correspondence to Per Soelberg Sorensen, MD, DMSc, Department of Neurology, Danish Multiple Sclerosis Center, 2082, Rigshospitalet, 9, Blegdamsvej, DK-2100 Copenhagen, Denmark. Tel: +45 35452080; fax: +45 35452626; e-mail: [email protected] Current Opinion in Neurology: June 2020 - Volume 33 - Issue 3 - p 262-270 doi: 10.1097/WCO.0000000000000811 Buy Metrics Abstract Purpose of review Based on the knowledge of disease mechanisms in the progressive course of multiple sclerosis and the experience from randomized clinical trials, we assessed the timing of disease-modifying therapy in patients with progressive multiple sclerosis to define the optimal window of opportunity for treatment of progressive multiple sclerosis. Recent findings In progressive multiple sclerosis both small molecules that cross the blood--brain barrier (siponimod) and monoclonal antibodies (ocrelizumab) have shown therapeutic efficacy and have been approved for treatment of progressive multiple sclerosis. However, the majority of phase II and phase III trials in progressive forms of multiple sclerosis have been negative, probably owing to either late start of treatment or use of drugs that are ineffective for treatment of progressive multiple sclerosis. Summary Results from phase II and III trials suggest that the window of opportunity for treatment of progressive multiple sclerosis with anti-inflammatory drugs is predominantly in the early phase of the progressive disease course when patients have lower age, shorter duration of progressive multiple sclerosis, and more pronounced clinical and MRI inflammatory activity. Ongoing trials of neuroprotective drugs may widen the window of opportunity by expanding targeted pathophysiologies. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.