Secondary Progressive Multiple Sclerosis: New Insights

In most cases, multiple sclerosis (MS) begins with a relapsing–remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and is termed secondary progressive multiple sclerosis (SMPS). Major differences exist between relapsing–remitting MS (RRMS) and SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, and challenges in the diagnosis and treatment of SPMS. We emphasize the criticality of conversion from a relapsing–remitting to a secondary progressive disease course not only because such conversion is evidence of disability progression, but also because, until recently, treatments that effectively reduced disability progression in relapsing MS were not proven to be effective in SPMS. Clear clinical, imaging, immunological, or pathological criteria marking the transition from RRMS to SPMS have not yet been established. Early identification of SPMS will require tools which, together with the use of appropriate treatments, may result in better long-term outcomes for the population of patients with SPMS.

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Interferon beta-1b — the first long-term effective treatment of relapsing-remitting and secondary progressive multiple sclerosis (MS)

Biopharmaceuticals, an Industrial Perspective ◽

10.1007/978-94-017-0926-2_7 ◽

1999 ◽

pp. 173-184 ◽

Cited By ~ 1

Author(s):

R. Horowski ◽

J.-F. Kapp ◽

M. Steinmayr ◽

St. Stuerzebecher

Keyword(s):

Multiple Sclerosis ◽

Effective Treatment ◽

Interferon Beta ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Relapsing Remitting

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Cost-effectiveness of different interferon beta products for relapsing-remitting and secondary progressive multiple sclerosis: Decision analysis based on long-term clinical data and switchable treatments

DARU Journal of Pharmaceutical Sciences ◽

10.1186/2008-2231-21-50 ◽

2013 ◽

Vol 21 (1) ◽

Cited By ~ 17

Author(s):

Shekoufeh Nikfar ◽

Abbas Kebriaeezadeh ◽

Rassoul Dinarvand ◽

Mohammad Abdollahi ◽

Mohammad-Ali Sahraian ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cost Effectiveness ◽

Decision Analysis ◽

Clinical Data ◽

Interferon Beta ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Relapsing Remitting

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PND36 Cost-Effectiveness of Different Interferon-Beta Therapies for Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: A Markov Model Based on Long-Term Clinical Data

Value in Health ◽

10.1016/j.jval.2012.08.1960 ◽

2012 ◽

Vol 15 (7) ◽

pp. A552

Author(s):

S. Nikfar ◽

A. Akbarisari ◽

A. Kebriaee ◽

R. Dinarvand ◽

M. Abdollahi

Keyword(s):

Multiple Sclerosis ◽

Cost Effectiveness ◽

Markov Model ◽

Clinical Data ◽

Interferon Beta ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Relapsing Remitting

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Repurposing Domperidone in Secondary Progressive MS

Neurology ◽

10.1212/wnl.0000000000011863 ◽

2021 ◽

pp. 10.1212/WNL.0000000000011863

Author(s):

Marcus W. Koch ◽

Kayla Sage ◽

Sharanjit Kaur ◽

Janet Kim ◽

Graziela Cerchiaro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Phase 2 ◽

Disability Progression ◽

Two Stage ◽

Serious Adverse Events ◽

Secondary Progressive ◽

Link Type

ObjectiveTo assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon two-stage design.MethodsWe enrolled patients in an open-label, Simon two-stage, single-center, phase 2, single-arm futility trial at the Calgary MS Clinic if they met the following criteria: age 18–60 years, SPMS, screening EDSS score of 4.0–6.5 and screening T25FW of 9 seconds or more. Patients received domperidone 10 mg QID for one year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by 20% or more at 12 months compared to at baseline. This trial is registered with ClinicalTrials.gov, number NCT02308137.ResultsBetween February 13, 2015 and January 3, 2020, 110 patients were screened, 81 received treatment, 64 completed follow-up, of whom 62 were analysed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40%, and above the pre-defined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients.ConclusionsDomperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon two-stage trial model may be a useful model for phase 2 studies in progressive MS.Classification of evidenceThis study provides Class III evidence that in individuals with secondary progressive multiple sclerosis participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.

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Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318783347 ◽

2018 ◽

Vol 4 (2) ◽

pp. 205521731878334 ◽

Cited By ~ 6

Author(s):

Francisco Coret ◽

Francisco C Pérez-Miralles ◽

Francisco Gascón ◽

Carmen Alcalá ◽

Arantxa Navarré ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Disease Modifying Therapies ◽

Relapsing Remitting ◽

Disease Modifying ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

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