Randomized study of antibodies to IFN-g and TNF-a in secondary progressive multiple sclerosis

2001 ◽  
Vol 7 (5) ◽  
pp. 277-284 ◽  
Author(s):  
S Skurkovich ◽  
A Boiko ◽  
I Beliaeva ◽  
A Buglak ◽  
T Alekseeva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Randomized Study ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Secondary Progressive ◽  
Number Of Patients ◽  
Scale Scores ◽  
Term Administration ◽  
Group A

Studies of cytokines in multiple sclerosis (MS) have shown that immune mechanisms connected with disturbance of the synthesis of cytokines probably play critical roles in the initiation and prolongation of MS. In a double-blind, placebo-controlled trial, 45 patients with active secondary progressive MS were randomized to three groups of 15 patients, each receiving a short course of antibodies to IFN-g, to tumor necrosis factor (TNF)-a, or a placebo. After 12 months with analysis of disability (Expanded Disability Status Scale scores), accompanied by interval determinations of lymphocyte subpopulations, cytokine production levels, MRI, and evoked potentials, it was found that only patients who received antibodies to IFN-g showed statistically significant improvement compared to the placebo group-a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1b, TNF-a, and IFN-g concentrations in supernatants of activated blood cells of these MS patients and an increase in TGF-b production). Neutralization of IFN-g could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-g and simultaneous use of antibodies to IFN-g together with IFN-b products are planned.

scholarly journals Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

2017 ◽  
Vol 19 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Gary Birnbaum
Keyword(s):  
Multiple Sclerosis ◽  
Acute Disease ◽  
Published Data ◽  
Secondary Progressive ◽  
Disease Modifying Therapy ◽  
Scale Scores ◽  
Group A ◽  
Multiple Variables ◽  
Disease Modifying ◽  
Group B

Background: Current disease-modifying therapies (DMTs) are of benefit only in people with relapsing forms of multiple sclerosis (RMS). Thus, safely stopping DMTs in people with secondary progressive MS may be possible. Methods: Two groups of patients with MS were studied. Group A consisted of 77 patients with secondary progressive MS and no evidence of acute central nervous system inflammation for 2 to 20 years. These patients were advised to stop DMTs. Group B consisted of 17 individuals with RMS who stopped DMTs on their own. Both groups were evaluated at treatment cessation and for a minimum of 1 year thereafter. Multiple variables were assessed to determine those that predicted recurrent acute disease. Results: Nine patients in group A (11.7%) and ten patients in group B (58.8%) had recurrent acute disease, almost always within 1 to 2 years of stopping treatment. The only variable of significance in group A distinguishing stable and relapsing patients was age (P = .0003), with relapsing patients being younger. Group B patients were younger and had significantly lower Expanded Disability Status Scale scores than group A, with no significant differences in age between relapsed and stable patients. Conclusions: The DMTs can be stopped safely in older patients with MS (≥7 decades) with no evidence of acute disease for 2 years or longer, with an almost 90% probability of remaining free of acute recurrence. The high proportion of untreated patients with RMS experiencing recurrent acute disease is consistent with published data.

Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis

1998 ◽  
Vol 4 (2) ◽  
pp. 74-78 ◽  
Author(s):  
B Dubois ◽  
M B D'Hooghe ◽  
K De Lepeleire ◽  
P Ketelaer ◽  
G Opdenakker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Tissue Type ◽  
Control Group ◽  
Double Blind ◽  
Gelatinase B ◽  
Double Blind Placebo ◽  
Secondary Progressive

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficaceous protease inhibitors than those used in the combination therapy described here.

Hopelessness Ratings in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

2002 ◽  
Vol 32 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Scott B. Patten ◽  
Luanne M. Metz
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Exact Probability ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Trial Participants ◽  
Over Time

Objective: Two recent randomized double-blind placebo controlled clinical trials of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial, evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS). Another, the SPECTRIMS trial, evaluated the same medication in secondary progressive (SP) MS. The objective of this analysis was to compare levels of hopelessness in persons with RRMS and SPMS, and to describe changes over time in the clinical trial participants. Method: Raw data from each clinical trial was obtained from the sponsor of the trials (Serono). Median BHS ratings, and the proportions at or above the BHS cut-point of 10 were calculated over a two (PRISMS) or three (SPECTRIMS) year period. Results: The analysis included n = 532 clinical trial participants. Ratings of hopelessness were higher in SPMS clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness were higher during follow-up than at baseline, in the SPMS group (McNemar's exact probability, p = 0.0015), but not in the RRMS group (McNemar's exact probability, p = 0.65). Depression was strongly associated with hopelessness in both RRMS ( z = 4.13, p < 0.001) and SPMS ( z = 5.24, p < 0.001). Conclusions: Hopelessness is associated with SPMS, and may increase over time in this group. Hopelessness may influence suicide risk in people with MS and may potentially have an impact on coping and quality of life. Additional research is necessary to define the clinical implications of hopelessness in persons with this condition.

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