Overview of London trial of intramuscular interferon-b1a in primary-progressive multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S56-S57 ◽  
Author(s):  
David H Miller ◽  
Siobhan M Leary ◽  
Alan J Thompson

This short monograph describes the rationale, design and outcome of a pilot study of beta interferon in patients with primary progressive MS. A total of 50 patients were studied for 2 years using a randomized, double-blinded, placebo -controlled design. There was an emphasis on using MRI measures to evaluate outcome. The study showed that with the numbers studied, useful data could be obtained on safety and on efficacy on certain MRI measures. A larger study would be required to evaluate treatment on disability in this patient cohort and further work is needed to elucidate the relationship between quantitative MR and clinical measures over the longer term.

2013 ◽  
Vol 20 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Regina Schlaeger ◽  
Marcus D’Souza ◽  
Christian Schindler ◽  
Leticia Grize ◽  
Ludwig Kappos ◽  
...  

Background: Currently no valid surrogate marker exists for primary progressive multiple sclerosis (PPMS). Objective: Our aim was to prospectively investigate multimodal evoked potentials (EPs) as markers and predictors of the disease course in PPMS. Methods: Twenty-two PPMS patients were prospectively examined with visual, somatosensory and motor EPs and Expanded Disability Status Scale (EDSS) assessments at baseline (T0) and at six-month intervals over three years. Spearman rank correlation was used to determine the relationship between EP measures and EDSS. The relationship between disease evolution and a numerical score derived from z-transformed EP-latencies ( s-EP-Q) and baseline characteristics was further assessed using multivariable linear regression analysis. Results: s-EP-Q correlated with EDSS score at all points in time in cross-sectional comparison (0.53≤rs ≤0.68; 0.0007≤p≤0.0232) and also longitudinally by trend ( rs=0.46, p=0.0740). The s-EP-QT0 correlated with the EDSS score at year 3 (T6) ( rs=0.77, p<0.0001). The s-EP-Q changes became statistically significant six months before corresponding changes were seen in the EDSS score. EDSST6 as predicted by EDSST6= −1.027+0.037* age+0.217* s-EP-QT0 + 0.695* EDSST0 correlated with the observed values ( rs=0.92, p<0.0001). Conclusions: Multimodal EPs correlate well with disability in PPMS, and allow some prediction of the disease course over three years. These findings support a role of EPs as surrogate markers in clinical trials in PPMS.


2016 ◽  
Vol 22 (13) ◽  
pp. 1750-1758 ◽  
Author(s):  
A Scalfari ◽  
C Lederer ◽  
M Daumer ◽  
R Nicholas ◽  
GC Ebers ◽  
...  

Background: The multiple sclerosis (MS) clinical course and relapses frequency before progression vary widely. Objective: To investigate the influence of age on the MS phenotype. Methods: Among 751 primary progressive (PP = 217) and secondary progressive (SP = 534) MS patients from the London Ontario database, we assessed the relationship of age on the relapse frequency and on the progressive phase evolution, and the impact of relapses on the age at onset of progression. Results: Age at onset did not influence the early attacks frequency, but patients younger at onset had larger number of total attacks before progression (age = 27.4, 31.0 and 32.8 mean years; ⩾4, 2–3 and 1 relapses, respectively) and longer latency to SP. Although frequent early relapses predicted younger age at SP onset, patients with no attacks (primary progressive multiple sclerosis (PPMS)), or 1, 2–3 and ⩾4 relapses during the relapsing-remitting phase started progressing at similar age (38.6, 41.3, 41.4 and 39.2 mean years, respectively). The age at onset of progressive phase did not affect its evolution. Conclusions: Age strongly influences the phenotype before progression. Relapsing-remitting patients younger at onset are more likely to display a predominantly inflammatory course, yet relapses number does not affect the age at onset of progression.


2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S62-S64 ◽  
Author(s):  
Xavier Montalban

This short monograph describes a trial of interferon b-1b in patients with primary progressive multiple sclerosis (PPMS) or transitional MS. Designed as a randomized, placebo -controlled pilot, the trial randomly placed 73 eligible patients into two groups, placebo or interferon b-1b 8 MIU given subcutaneo usly every other day for two years. Significant differences favouring interferon b-1b in the MSFC score, T2 lesion volume and T1 lesion volume at 24 months were observed. Further study of interferon b-1b therapy in PPMS patients is warranted.


2004 ◽  
Vol 10 (4) ◽  
pp. 376-380 ◽  
Author(s):  
J Sastre-Garriga ◽  
M Comabella ◽  
L Brieva ◽  
A Rovira ◽  
M Tintoré ◽  
...  

Background: An increase in MMP-9 levels has been found in relapsing-remitting (RR) multiple sclerosis (MS) showing correlation with magnetic resonance (MR) parameters mainly during relapses. However, data regarding primary progressive (PP) MS is scarce. Objectives: To determine both the pro and active forms of MMP-9 in PPMS and transitional progressive (TP) MS, RRMS and healthy controls (HC), and to assess the relationship between MMP-9 levels and clinical and radiological variables in PP/TPMS. Methods: 73 patients with PP/TPMS, 50 RRMS and 43 HC were studied. Levels of pro and active forms of MMP-9 in serum were measured with ELISA. EDSS and MSFC scores were recorded and T2- and T1-weighted MR scans were obtained at the time of blood sampling and one and two years later for PP/TP MS cases. Results: MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC. MMP-9 levels were significantly lower in PP/TPMS compared to RRMS(P-0.026) and HC (P- 0.001). No significant correlations were found between MMP-9 levels and clinical scores or radiological parameters. Conclusions: These results point to different regulatory mechanisms of MMP-9 production and/or activity between PP/TPMS and RRMS.


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