scholarly journals Outcome Measures in Relapsing-Remitting Multiple Sclerosis: Capturing Disability and Disease Progression in Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Amy M. Lavery ◽  
Leonard H. Verhey ◽  
Amy T. Waldman
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Neurodegenerative Disease ◽  
Disease Progression ◽  
Outcome Measures ◽  
Primary Endpoint ◽  
Surrogate Endpoints ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that manifests as acute relapses and progressive disability. As a primary endpoint for clinical trials in MS, disability is difficult to both characterize and measure. Furthermore, the recovery from relapses and the rate of disability vary considerably among patients. Given these challenges, investigators have developed and studied the performance of various outcome measures and surrogate endpoints in MS clinical trials. This review defines the outcome measures and surrogate endpoints used to date in MS clinical trials and presents challenges in the design of both adult and pediatric trials.

CONCERTO: A randomized, placebo-controlled trial of oral laquinimod in relapsing-remitting multiple sclerosis

2021 ◽  
pp. 135245852110328
Author(s):  
Giancarlo Comi ◽  
Yuval Dadon ◽  
Nissim Sasson ◽  
Joshua R Steinerman ◽  
Volker Knappertz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Adaptive Immune Response ◽  
Secondary Endpoint ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Interventions targeting the adaptive immune response are needed in multiple sclerosis (MS). Objective: Evaluate laquinimod’s efficacy, safety, and tolerability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: CONCERTO was a randomized, double-blind, placebo-controlled, phase-3 study. RRMS patients were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 or 1.2 mg or placebo for ⩽24 months ( n = 727, n = 732, and n = 740, respectively). Primary endpoint was time to 3-month confirmed disability progression (CDP). The laquinimod 1.2-mg dose arm was discontinued (1 January 2016) due to cardiovascular events at high doses. Safety was monitored throughout the study. Results: CONCERTO did not meet the primary endpoint of significant effect with laquinimod 0.6-mg versus placebo on 3-month CDP (hazard ratio: 0.94; 95% confidence interval: 0.67–1.31; p = 0.706). Secondary endpoint p values were nominal and non-inferential. Laquinimod 0.6 mg demonstrated 40% reduction in percent brain volume change from baseline to Month 15 versus placebo ( p < 0.0001). The other secondary endpoint, time to first relapse, and annualized relapse rate (an exploratory endpoint) were numerically lower (both, p = 0.0001). No unexpected safety findings were reported with laquinimod 0.6 mg. Conclusion: Laquinimod 0.6 mg demonstrated only nominally significant effects on clinical relapses and magnetic resonance imaging (MRI) outcomes and was generally well tolerated. Clinical trial registration number: ClinicalTrials.gov (NCT01707992).

Relationship between Sustained Disability Progression and Functional System Scores in Relapsing-Remitting Multiple Sclerosis: Analysis of Placebo Data from Four Randomized Clinical Trials

2015 ◽  
Vol 44 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Thomas Scott ◽  
Ping Wang ◽  
Xiaojun You ◽  
Monica Mann ◽  
Bjørn Sperling
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Functional System ◽  
Validity And Reliability ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains. Methods: A post hoc analysis was performed on data from placebo-treated RRMS patients from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed. Results: The majority of patients experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains. Conclusion: The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression.

scholarly journals Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

2021 ◽  
Vol 13 ◽  
pp. 117957352110507
Author(s):  
Qi Wu ◽  
Qin Wang ◽  
Jennifer Yang ◽  
Jacob WS Martens ◽  
Elizabeth A Mills ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: The long-term prognosis of relapsing-remitting multiple sclerosis (RRMS) is usually unfavorable as most patients transition to secondary progressive multiple sclerosis (SPMS) with accumulative disability. A rare form of non-progressive multiple sclerosis (MS) also exists, known as benign MS (BMS or NPMS), which lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after 15 years of disease onset without treatment. Purpose: Our study aims to identify soluble plasma factors predicting disease progression in multiple sclerosis (MS). Research Design and Study Sample: We utilized Luminex multiplex to analyze plasma levels of 33 soluble factors, comparing 32 SPMS patients to age-, sex-, and disease duration-matched non-progressive BMS patients, as well as to RRMS patients and healthy controls. Results: Plasma levels of EGF, sCD40L, MCP1/CCL2, fractalkine/CX3CL1, IL-13, Eotaxin, TNFβ/LTα, and IL-12p40 were significantly different between the various types of MS. Plasma sCD40L was significantly elevated in SPMS compared to BMS and RRMS. The combination of MCP1/CCL2 and sCD40L discriminated between RRMS and SPMS. MCP1/CCL2 was found to be the most effective classifier between BMS and RRMS, while BMS was most effectively distinguished from SPMS by the combination of sCD40L and IFNγ levels. Conclusions: These differences may facilitate personalized precision medicine and aid in the discovery of new therapeutic targets for disease progression through the improvement of patient stratification.

ECTRIMS/ACTRIMS 2017: Closing in on neurorepair in progressive multiple sclerosis

2018 ◽  
Vol 24 (6) ◽  
pp. 696-700 ◽  
Author(s):  
David Kremer ◽  
Patrick Küry ◽  
Hans-Peter Hartung
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Progressive Multiple Sclerosis ◽  
Treatment Goal ◽  
European Committee ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Tool Set ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Stimulation Of

Background: While there is now a multitude of potent medications for relapsing-remitting multiple sclerosis (RRMS), effective therapies targeting neurodegeneration in progressive multiple sclerosis types are still lacking. Stimulation of neurorepair in this disease remains a pathogenetically defined treatment goal. However, therapeutic progress is slowed by the still inadequate tool set to capture “regeneration/repair” in MS and to define appropriate outcomes in clinical trials. Objectives: In this review, we discuss studies investigating promising regenerative agents for progressive MS which were recently presented during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 meeting in Paris.

Sign in / Sign up

Export Citation Format

Share Document