Diagnosis and treatment of progressive multiple sclerosis: A position paper

Authors: Carlo Pozzilli ^1 2, Maura Pugliatti ^3 4, Patrick Vermersch ⁵, Nikolaos Grigoriadis ⁶, Mona Alkhawajah ⁷, Laura Airas ^8 9, Celia Oreja-Guevara ^10 11

1) Multiple Sclerosis Center, Sant’Andrea Hospital, Rome, Italy, 2) Department of Human Neuroscience, University Sapienza, Rome, Italy, 3) Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy, 4)Interdepartmental Center of Research for Multiple Sclerosis and Neuro-inflammatory and Degenerative Diseases, University of Ferrara, Ferrara, Italy, 5) Inserm U1172 LilNCog, CHU Lille, FHU Precise, University of Lille, Lille, France, 6) Laboratory of Experimental Neurology and Neuroimmunology, Second Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, 7) Section of Neurology, Neurosciences Center, King Faisal Specialist Hospital and Research Center, College of Medicine, Al Faisal University, Riyadh, Kingdom of Saudi Arabia, 8) Division of Clinical Neurosciences, University of Turku, Turku, Finland, 9) Neurocenter of Turku University Hospital, Turku, Finland, 10) Department of Neurology, Hospital Clinico San Carlos, IdISSC, Madrid, Spain, 11) Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain.

Abstract

Background and purpose: Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians. This article examines how the diagnostic definitions of progressive MS impact clinical research, the design of clinical trials and, ultimately, treatment decisions.

Methods: We carried out an extensive review of the literature highlighting differences in the definition of progressive forms of MS, and the importance of assessing the extent of the ongoing inflammatory component in MS when making treatment decisions.

Results: Inconsistent results in phase III clinical studies of treatments for progressive MS, may be attributable to differences in patient characteristics (e.g., age, clinical and radiological activity at baseline) and endpoint definitions. In both primary and secondary progressive MS, patients who are younger and have more active disease will derive the greatest benefit from the available treatments.

Conclusions: We recommend making treatment decisions based on the individual patient’s pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. Because the definition of progressive MS differs across clinical studies, careful selection of eligibility criteria and study endpoints is needed for future studies in patients with progressive MS.

Keywords: diagnosis; multiple sclerosis; primary progressive; secondary progressive; treatment.

© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.