scholarly journals Teriflunomide Safety and Efficacy in Advanced Progressive Multiple Sclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Vanessa F. Moreira Ferreira ◽  
Danielle Caefer ◽  
Natalie Erlich-Malona ◽  
Brian C. Healy ◽  
Tanuja Chitnis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Confidence Interval ◽  
Glatiramer Acetate ◽  
Progressive Multiple Sclerosis ◽  
Small Sample ◽  
Cox Proportional Hazards Model ◽  
Safety And Efficacy ◽  
Status Score ◽  
Disability Status ◽  
Multiple Sclerosis Population

Objectives. To explore the safety and efficacy profile of teriflunomide in progressive multiple sclerosis. Methods. We conducted a single-center retrospective observational analysis of a progressive multiple sclerosis population, assessing safety and efficacy in patients treated at least one year with teriflunomide or glatiramer acetate. Sustained progression of expanded disability status scale and sustained worsening of timed 25-foot walk were compared using a Cox proportional hazards model. Results. Teriflunomide group ( n = 29 ) mean characteristics: age = 58 years ( SD ± 7.6 ), disease   duration = 16.7 years ( SD ± 9.5 ), expanded   disability   status   score = 5.9 ( SD ± 1.3 ), and follow − up = 32.4 months ( SD ± 13.6 ). Glatiramer acetate group ( n = 30 ) mean characteristics: age = 52.4 years ( SD ± 11.3 ), disease   duration = 15.1 years ( SD ± 10.4 ), expanded   disability   status   score = 5.7 ( SD ± 1.6 ), and follow − up = 46.9 months ( SD ± 43.9 ). Both treatments were well tolerated without serious side effects. After adjustment for age, sex, and baseline expanded disability status score, sustained expanded disability status score progression did not differ between groups ( hazard   ratio = 1.17 ; 95% confidence interval: 0.45, 3.08; p = 0.75 ). Sustained timed 25-foot walk worsening after adjustment also did not differ ( hazard   ratio = 0.56 ; 95% confidence interval: 0.2, 1.53; p = 0.26 ). Conclusion. In an advanced progressive multiple sclerosis population, no substantial differences in tolerability, safety, sustained EDSS progression, or sustained T25FW worsening over time were observed between glatiramer acetate and teriflunomide-treated groups. The small sample precluded definitive determination.

scholarly journals Effectiveness and safety of dimethyl fumarate in progressive multiple sclerosis

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110108
Author(s):  
Vanessa F Moreira Ferreira ◽  
Yanqing Liu ◽  
Brian C Healy ◽  
James M Stankiewicz
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Dimethyl Fumarate ◽  
Progressive Multiple Sclerosis ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Cox Proportional Hazards Models ◽  
Disability Status ◽  
Clinically Significant ◽  
One Year

Background There is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population. Objective To analyze the safety and effectiveness of DMF in patients with PMS. Methods We used Cox proportional hazards models to compare the time to confirmed worsening and improvement on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) between patients treated with DMF and glatiramer acetate (GA) for at least one year. Results We included 46 patients treated with DMF and 42 patients treated with GA. The safety and tolerability of GA and DMF were consistent with established profiles. There was no difference in confirmed EDSS progression. A trend towards reduced T25FW was seen in the DMF compared to GA after adjustment (HR = 0.86; 95% CI:0.37, 1.98; p = 0.72 and HR = 0.60; 95% CI:0.27, 1.34; p = 0.21, respectively). Conclusion Dimethyl fumarate showed a trend towards reduction in T25FW but no evidence of clinically significant impact on EDSS. The small sample precluded definitive determination.

scholarly journals Benefit with methylprednisolone in continuous pulsetherapy in progressive primary form of multiple sclerosis: study of 11 cases in 11 years

2008 ◽  
Vol 66 (2b) ◽  
pp. 350-353 ◽  
Author(s):  
Edmar A.S. de Araújo ◽  
Marcos R. Gomes de Freitas
Keyword(s):  
Multiple Sclerosis ◽  
Glucose Solution ◽  
Progressive Multiple Sclerosis ◽  
Small Sample ◽  
Primary Progressive Multiple Sclerosis ◽  
The Third ◽  
Weekly Session ◽  
Clinical Worsening ◽  
Progressive Course ◽  
Primary Form

Primary progressive multiple sclerosis (PPMS) is defined clinically with a progressive course from onset. There is no approved treatment for the PPMS. Methylprednisolone IV (MP) hastens the recovery from MS relapses. We studied 11 patients that met the MacDonald's diagnostic criteria for PPMS. The dose of MP was 30 mg/kg in 250 mL of glucose solution in three consecutive days during the first week, two doses during the second and one dose in the third week. One weekly session for eight consecutive weeks was given. After, a once-a week/eight-week interval was maintained. The medium EDSS before treatment was 6.2, and after 11.2 years of treatment, the EDSS was 4.9. Although we studied a small sample of PPMS we may conclude that therapy with IVMP prevents clinical worsening of MS in the majority of patients with improvement in EDSS scores.

scholarly journals Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Isobel A. Scarisbrick ◽  
Rachel Linbo ◽  
Alexander G. Vandell ◽  
Mark Keegan ◽  
Sachiko I. Blaber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Neurons ◽  
Serine Proteases ◽  
Serum Levels ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Neurite Retraction ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Potential Activity

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

scholarly journals Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

2017 ◽  
Vol 24 (4) ◽  
pp. 501-511 ◽  
Author(s):  
Jeffrey A Cohen ◽  
Peter B Imrey ◽  
Sarah M Planchon ◽  
Robert A Bermel ◽  
Elizabeth Fisher ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Scale Score ◽  
Pilot Trial ◽  
Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Serious Adverse Events ◽  
Mesenchymal Stem Cell Transplantation ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri

Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0–6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1–2 × 106 MSCs/kg were thawed and administered IV. Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1–3 passages) was 1.9 × 106 MSCs/kg (range, 1.5–2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

scholarly journals Improved relapse recovery in paediatric compared to adult multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2733-2741
Author(s):  
Tanuja Chitnis ◽  
Greg Aaen ◽  
Anita Belman ◽  
Leslie Benson ◽  
Mark Gorman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional System ◽  
Progressive Multiple Sclerosis ◽  
Age Related ◽  
Younger Age ◽  
Disability Status ◽  
The Us ◽  
The Difference ◽  
Effect Of Age

Abstract Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.

scholarly journals Personal and societal costs of multiple sclerosis in the UK: A population-based MS Registry study

2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090172 ◽  
Author(s):  
Richard S Nicholas ◽  
Martin L Heaven ◽  
Rodden M Middleton ◽  
Manoj Chevli ◽  
Ruth Pulikottil-Jacob ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
United Kingdom ◽  
Disease Severity ◽  
Medical Costs ◽  
Medical Interventions ◽  
The United Kingdom ◽  
Status Score ◽  
Impact Scale ◽  
Patient Reported ◽  
Disability Status

Objectives To investigate through survey and data linkage, healthcare resource use and costs (except drugs), including who bears the cost, of multiple sclerosis in the United Kingdom by disease severity and type. Methods The United Kingdom Multiple Sclerosis Register deployed a cost of illness survey, completed by people with multiple sclerosis and linked this with data within the United Kingdom Multiple Sclerosis Register and from their hospital records. Resource consumption was categorised as being medical or non-medical and costed by National Health Service and social services estimates for 2018. Results We calculated £509,003 in non-medical costs over a year and £435,488 in medical costs generated over 3 months. People with multiple sclerosis reported self-funding 75% of non-medical costs with non-medical interventions having long-term potential benefits. Costs increased with disability as measured by patient-reported Expanded Disability Status Score and Multiple Sclerosis Impact Scale, with Multiple Sclerosis Impact Scale physical being a more powerful predictor of costs than the patient-reported Expanded Disability Status Score. Two distinct groups were identified: medical and non-medical interventions ( n = 138); and medical interventions only ( n = 399). The medical and non-medical group reported increased disease severity and reduced employment but incurred 80% more medical costs per person than the medical-only group. Conclusions The importance of disability in driving costs is illustrated with balance between medical and non-medical costs consistent with the United Kingdom health environment. People with multiple sclerosis and their families fund a considerable proportion of non-medical costs but non-medical interventions with longer term impact could affect future medical costs.

scholarly journals Safety and Tolerability of Subcutaneous Cladribine Therapy in Progressive Multiple Sclerosis

1998 ◽  
Vol 25 (4) ◽  
pp. 295-299 ◽  
Author(s):  
R. Selby ◽  
J. Brandwein ◽  
P. O'Connor
Keyword(s):  
Multiple Sclerosis ◽  
Lymphocyte Count ◽  
Antineoplastic Agent ◽  
Absolute Lymphocyte Count ◽  
Progressive Multiple Sclerosis ◽  
Disability Status ◽  
Chronic Progressive Multiple Sclerosis ◽  
Clinically Significant ◽  
One Year ◽  
Post Therapy

ABSTRACT:Objective:To evaluate the safety and tolerability of subcutaneous (s.c.) cladribine therapy in patients with chronic progressive multiple sclerosis (CPMS), and to evaluate the effects on lymphocyte subsets.Background:Cladribine, a synthetic antineoplastic agent with immunosuppressive effects, may favourably affect the course of CPMS. However results of a previous reported clinical trial showed significant myelosuppression in some patients.Design/Methods:19 patients with severe (mean extended disability status score [EDSS] = 6.7) CPMS were treated on a compassionate basis with cladribine 0.07 mg/kg/ day s.c. for 5 days per cycle, repeated every 4 weeks for a total of 6 cycles. Patients underwent clinical evaluation, EDSS, and hematologic analysis before, during, and following therapy.Results:The treatment was very well tolerated with no clinically significant side effects observed. Between baseline and the end of cycle 6, mean decreases were noted in absolute lymphocyte count from 1697 to 463 (p = 0.000012), CD4 count from 865 to 187 (p = 0.0000008), CD8 from 418 to 165 (p = 0.005) and CD19 from 197 to 26 (p = 0.000002). Platelet, granulocyte and RBC counts were unaffected. Approximately one year after completion of therapy, some recovery of CD4 and CD8 counts had occurred although both counts remained suppressed compared to baseline (302 and 227 respectively); the CD19 count had recovered essentially to normal by one year. EDSS scores post-therapy revealed some deterioration in 8 patients and stable scores in the remaining 11. Global patient evaluations of the treatment were mixed.Conclusions:Cladribine therapy, at lower doses than previously reported, was remarkably well tolerated in CPMS, with no significant myelosuppression. Profound effects occurred in total lymphocyte count and CD4, CD8 and CD19 subsets.

Predicting risk of secondary progression in multiple sclerosis: A nomogram

2018 ◽  
Vol 25 (8) ◽  
pp. 1102-1112 ◽  
Author(s):  
Ali Manouchehrinia ◽  
Feng Zhu ◽  
Daniela Piani-Meier ◽  
Markus Lange ◽  
Diego G Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Predictive Ability ◽  
Progressive Multiple Sclerosis ◽  
Patient Counselling ◽  
Derivation Cohort ◽  
Efficacious Treatment ◽  
Disability Status ◽  
Using Data ◽  
Worse Prognosis

Objectives: We aimed at designing a nomogram, a prediction tool, to predict the individual’s risk of conversion to secondary progressive multiple sclerosis (SPMS) at the time of multiple sclerosis (MS) onset. Methods: One derivation and three validation cohorts were established. The derivation cohort included 8825 relapsing-onset MS patients in Sweden. A nomogram was built based on a survival model with the best statistical fit and prediction accuracy. The nomogram was validated using data from 3967 patients in the British Columbia cohort, 176 patients in the ACROSS and 2355 patients in FREEDOMS/FREEDOMS II extension studies. Results: Sex, calendar year of birth, first-recorded Expanded Disability Status Scale (EDSS) score, age at the first EDSS and age at disease onset showed significant predictive ability to estimate the risk of SPMS conversion at 10, 15 and 20 years. The nomogram reached 84% (95% confidence intervals (CIs): 83–85) internal and 77% (95% CI: 76–78), 77% (95% CI: 70–85) and 87% (95% CI: 84–89) external accuracy. Conclusions: The SPMS nomogram represents a much-needed complementary tool designed to assist in decision-making and patient counselling in the early phase of MS. The SPMS nomogram may improve outcomes by prompting timely and more efficacious treatment for those with a worse prognosis.

scholarly journals Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

2018 ◽  
Vol 24 (14) ◽  
pp. 1862-1870 ◽  
Author(s):  
Edward J Fox ◽  
Clyde Markowitz ◽  
Angela Applebee ◽  
Xavier Montalban ◽  
Jerry S Wolinsky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Upper Extremity ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Intention To Treat ◽  
Disability Status ◽  
Upper Extremity Impairment ◽  
Post Hoc

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS). Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO. Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT. Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses. Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.

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