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.

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.

Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis - outline of a double-blind randomized, placebo-controlled trial

1997 ◽  
Vol 3 (2) ◽  
pp. 149-152 ◽  
Author(s):  
D. Poehlau ◽  
J. Federlein ◽  
T. Postert ◽  
M. Sailer ◽  
F. Bethke ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Ivig Treatment ◽  
Double Blind ◽  
Disability Status ◽  
Chronic Progressive Multiple Sclerosis ◽  
Phase Iii Study ◽  
Two Measures

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point: (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

scholarly journals Risk factors for fingolimod-induced lymphopenia in multiple sclerosis

2018 ◽  
Vol 4 (1) ◽  
pp. 205521731875969 ◽  
Author(s):  
Ryohei Ohtani ◽  
Masahiro Mori ◽  
Tomohiko Uchida ◽  
Akiyuki Uzawa ◽  
Hiroki Masuda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Disease Duration ◽  
Area Under The Curve ◽  
Absolute Lymphocyte Count ◽  
Medication History ◽  
Disability Status ◽  
History Of ◽  
One Year

Background Lymphopenia is a well-known adverse event of fingolimod, a disease-modifying drug for multiple sclerosis (MS). Objectives The objective of this paper is to investigate risk factors for predicting fingolimod-induced lymphopenia in MS by frequent hematological monitoring. Methods We retrospectively reviewed data of fingolimod-treated MS patients. Data assessed were sex, age, disease duration, medication history, body mass index, all attacks, Kurtzke’s Expanded Disability Status Scale score, and absolute lymphocyte count (ALC) within two days before initiating fingolimod (baseline), on the day after first administration (day 2), and at least every other month after initiating fingolimod therapy. Results Of 41 MS patients, marked lymphopenia (ALC <200/µl) was confirmed in 12 patients (lymphopenia group) within one year. A significantly more frequent history of treatment with any interferon-beta and lower median baseline ALC was observed in the lymphopenia group than in the non-lymphopenia group ( n = 29) (91.7% vs. 44.8%; p = 0.006 and 1469/µl vs. 1879/µl; p = 0.005). An ALC of ≤952/μl on day 2 was the most responsible risk factor for predicting marked lymphopenia (sensitivity, 92%; specificity, 76%; area under the curve, 0.823; p < 0.001). Conclusions Low baseline ALC and treatment history with any interferon-beta were risk factors for fingolimod-induced lymphopenia, possibly predicted from ALC on day 2.

Low-dose oral methotrexate in chronic progressive multiple sclerosis: Analyses of serial MRIs

Neurology ◽  
1996 ◽  
Vol 47 (5) ◽  
pp. 1153-1157 ◽  
Author(s):  
D.E. Goodkin ◽  
R.A. Rudick ◽  
S. V. Medendorp ◽  
M.M. Daughtry ◽  
C. Van Dyke
Keyword(s):  
Multiple Sclerosis ◽  
Low Dose ◽  
Progressive Multiple Sclerosis ◽  
Oral Methotrexate ◽  
Chronic Progressive Multiple Sclerosis ◽  
Dose Oral

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.

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