Treatment of Patients with Multiple Sclerosis Transitioning Between Relapsing and Progressive Disease

Abstract

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system with a wide variety of clinical phenotypes. In spite of the phenotypic classification of MS patients, current data provide evidence that diffuse neuroinflammation and neurodegeneration coexist in all MS forms, the latter gaining increasing clinical relevance in progressive phases. Given that the transition phase of relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) is not well defined, and widely accepted criteria for SPMS are lacking, randomised controlled trials (RCTs) specifically designed for the transition phase have not been conducted. This review summarizes primary and secondary analyses and reports derived from phase III prospective clinical RCTs listed in PubMed of compounds authorised through the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of MS. The best data are available for interferon beta-1a (IFNb-1a) subcutaneous (s.c.), IFNb-1b s.c., mitoxantrone and siponimod, the latter being the most modern compound with likely the best risk-to-effect ratio. Moreover, there is a labels discrepancy for many disease-modifying treatments (DMTs) between the FDA and EMA, which have to be taken into consideration when opting for a specific DMT.

Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials

“…Many patients that most clinicians would characterize as RRMS rather than SPMS experience low-level, non-obvious progression, which is not associated with relapses 1 . To clarify this complex terminology, new terms have been coined to distinguish the way disability accumulates in patients depending on the disease course: relapse-associated worsening (RAW) describes fixed neurological deficits that occurred during a relapse with an incomplete remission on the one hand and progression independent of relapse activity (PIRA) on the other hand 2 – 5 . Recent analyses from an extensive data set show that both RAW and PIRA contribute to overall disability accumulation.…”

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis—A Real-World Scenario

“…The introduction of S1P modulators has been a success in the treatment of not only relapsing-remitting MS but also in the treatment of secondary progressive MS [28,29]. In addition to siponimod, ozanimod and ponesimod functionally antagonise S1P receptors 1 and 5, whilst the first-generation S1P fingolimod functionally antagonises S1P receptors As secondary outcomes, we monitored immunoglobulin and lymphocyte levels longitudinally under anti-CD20 treatment.…”

Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis

“…The current classification of MS encompasses four primary phases: clinically isolated syndrome, relapsing-remitting phase (RRMS), secondary progressive phase (SPMS), and primary progressive phase (PPMS). However, there is significant overlap among these stages, and the transitions between them remain unclear [ 4 , 5 , 6 ]. RRMS, which affects approximately 80% of patients, is characterized by inflammation, demyelination, and intermittent episodes of neurological dysfunction.…”