Twice Weekly Versus Daily Glatiramer Acetate: Results of a Randomized, Rater-Blinded Prospective Clinical Trial Clinical and MRI Study in Relapsing-Remitting MS
Christina Caon, Jai Perumal, Alexandros Tselis, Wendy Ching, Fen Bao, Zahid Latif, Imad Zak, Omar Khan, Detroit, MI
OBJECTIVE: To investigate in a small pilot study the safety, tolerability, and efficacy of glatiramer acetate (GA) 20 mg injected subcutaneously (SC) twice a week versus GA administered 20 mg SC daily in RRMS.
BACKGROUND: The optimal dose of GA in RRMS remains unknown. We have previously shown that GA administered on alternate days appears to be as effective as daily GA. There is considerable interest in identifying the optimal dose of GA in RRMS.
DESIGN/METHODS: We conducted a prospective, randomized, rater-blinded 2 year study to compare GA 20 mg SC twice a week to GA 20 mg SC daily. RRMS patients receiving GA 20 mg SC daily for at least one year were randomized to either continue in the same fashion or switch to GA 20 mg SC twice weekly. EDSS were recorded every 6 months and to confirm relapses, while brain MRI scans were done at baseline and month 24.
RESULTS: 48 RRMS were randomized into equal groups of GA 20 mg SC daily or GA 20 mg SC twice-weekly. Both groups were well-matched. After two years, the annualized relapse rate, mean EDSS, proportion of relapse-free patients, and the proportion of patients without disease progression were similar in the two groups. Brain MRI also did not demonstrate any significant changes in T2W or T1W lesion, or in the percentage brain volume change. However, the incidence of lipoatrophy, local injection site reactions, and immediate-post injection systemic reactions were significantly lower in the GA twice-weekly group.
CONCLUSIONS/RELEVANCE: This study provides further evidence that GA administered less frequently than daily may be as efficacious and better tolerated than GA administered daily. This may have a significant impact in the clinical use of GA. Larger, multi-center studies are warranted to confirm our findings and investigate the optimal dose of GA in RRMS.
http://www.abstracts2view.com/aan/view. ... 0L_S11.002
Omega-3 Fatty Acids Treatment in Relapsing-Remitting Multiple Sclerosis
Kjell-Morten Myhr, Sjur Reinertsen, Bergen, Norway, Antonie Giæver Beiske, Lørenskog, Norway, Harald Hovdal, Trondheim, Norway, Rune Midgard, Molde, Norway, Frøydis Dalene, Skien, Norway, Jan Schepel, Haugesund, Norway, Grete Kleveland, Lillehammer, Norway, Halfdan Kierulf, Oslo, Norway, Randi Eikeland, Arendal, Norway, Alla Bru, Stavanger, Norway, Olaf Henriksen, Bodø, Norway, Terje Kristensen,, Fredrikstad, Norway, Astrid Edland, Ingrid Bjørnå, Drammen, Norway , Søren Jacob Bakke, Oslo, Norway, Tom Pedersen, Tønsberg, Norway, Finn Lilleås, Bård Bjørnarå, Inge Christoffer Olsen, Rita Malmo Nilsen, Oslo, Norway, Kristian Bjerve, Trondheim, Norway
OBJECTIVE: To analyze the efficacy of omega-3 fatty acids treatment in relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: Polyunsaturated fatty acids have been reported to be beneficial for MS patients. We performed a randomized, placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids in RRMS.
DESIGN/METHODS: A total of 92 RRMS patients were randomized for 6 months daily treatment with omega-3 fatty acids (Triomar) or placebo (corn oil) capsules. After 6 months, both groups received in addition interferon-beta (IFNB) 44 mcg sc (Rebif) thrice weekly for another 18 months. Monthly gadolinium enhanced magnetic resonance imaging (MRI) was performed for 9 months and after 12 and 24 months. We recorded relapse rate, disability progression (Expanded Disability Status Scale - EDSS), fatigue (Fatigue Severity Scale - FSS), quality of life (QoL, SF-36), Multiple Sclerosis Functional Composite (MSFC) and safety.
RESULTS: The cumulative number of enhancing MRI lesions during the first 6 months were similar in the omega-3 group compared to the placebo group (p=0.35). The number of new enhancing MRI lesions were significantly reduced (p<0.0001) after initiation of IFNB therapy, similar in both groups. No differences in number of relapses were detected after 6 months (p=0.54) and 24 months (p=0.72). Disability progression (1.0 EDSS point) after 6 months were recorded in 13% of the omega-3 patients compared to 10% of the placebo patients (p=0.74), and 30 % in both groups had progressed after 24 months. No differences were detected in fatigue, MSFC or QoL scores, and no safety concerns appeared. Serum analyzes of fatty acids showed a significant increase in omega-3 fatty acids (p<0.001) and a corresponding reduction in omega-6 fatty acids (p<0.001) in the omega-3 treated patients compared to the placebo group.
CONCLUSIONS/RELEVANCE: No beneficial effects on disease activity were detected from omega-3 fatty acids when compared to placebo (corn oil). IFNB reduced MRI disease activity as expected.
http://www.abstracts2view.com/aan/view. ... 0L_P04.209
Pilot Phase I/II Clinical Trial with Autologous Mesenchymal Stem Cells in Patients with Multiple Sclerosis and Amyotrophic Lateral Sclerosis
Dimitrios Karussis, Jerusalem, Israel, Clementine Karageorgiou, Athens, Greece, Basan Gowda-Kurkalli, Tel Aviv, Israel, Adi Vaknin-Dembinsky, John Moshe Gomori, Ibrahim Kassis, Panayiota Petrou, Jerusalem, Israel, Jeff Bulte, Baltimore, MD, Shimon Slavin, Tel Aviv, Israel
OBJECTIVE: A phase I/II open clinical trial was designed to evaluate the feasibility and safety of intrathecal and intravenous administration of autologous MSCs in patients with severe multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).
BACKGROUND: Mesenchymal stromal cells (MSC) have shown neuroprotective and immunomodulatory effects in animal models.
DESIGN/METHODS: 15 MS patients (mean EDSS=6.71.05) and 19 ALS patients (mean ALSFRS=20.268.56), were enrolled. Following culture, a mean number of 63.22.5x106 purified MSC was injected intrathecally (n=35) and intravenously (n=14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide (SPIO) formulation Feridex.
RESULTS: In 21 patients there were injection-related side effects consisting of transient mild fever and headache. No major side effects were reported during a follow up period of up to 25 months. The mean ALSFRS remained stable during the 6 first months of observation, whereas the mean EDSS score improved from 6.71.05 to 5.91.6 at 6 months. MR imaging clearly visualized the MSCs in the occipital horns of the ventricles at 24 hours post injection. and indicated a possible migration of Feridex-labeled cells in the meninges, the subarhachnoid space and the spinal cord parenchyma. Immunological analysis in 12 of the patients, revealed a 72% increase in the proportion of CD4+CD25+ regulatory T cells, a 63% decrease in the proliferative responses of lymphocytes (accompanied by a reduction in the IFNg and IL-17 production) and a 30-60% reduction of CD40, CD83, CD86, and HLA-DR expression on myeloid dendritic cells, at 24hrs following MSC transplantation.
CONCLUSIONS/RELEVANCE: Our findings suggest that intrathecal and intravenous injection of MSC in patients with MS and ALS, is a clinically feasible and relatively safe procedure. MSC treatment resulted in immediate immunomodulatory effects. Further controlled studies and longer observation periods are needed to evaluate the long term safety and the potential clinical efficacy of MSC treatment.
http://www.abstracts2view.com/aan/view. ... 0L_S21.006
Variations in the Gender Ratio of Multiple Sclerosis Linked to Converging Smoking Trends in Men and Women
Natalia Palacios, Boston, MA, Alvaro Alonso, Minneapolis, MN, Henrik Bronnum-Hansen, Coppenhagen, Denmark, Alberto Ascherio, Boston, MA
OBJECTIVE: To examine if a time-dependent relationship exists between changing female-to male ratios of smoking and Multiple Sclerosis (MS) in worldwide birth cohorts from previously published studies.
BACKGROUND: Smoking behavior in industrialized nations has changed dramatically over the second half of the 20th century, with diverging patterns in male and female smoking rates. During the same time period, an increase in the female to male ratio in MS incidence has been reported. We examined whether MS incidence in the two genders changed concomitantly with smoking, as would be expected if smoking truly increased MS risk.
DESIGN/METHODS: We identified relevant studies reporting male and female age-specific incidence of MS throughout the world using within-country birth cohorts as units of observation. For each country and birth cohort, we then estimated the male to female ratio in MS incidence, and correlated these ratios with the corresponding male to female ratios in smoking behavior obtained from national statistics. In addition, in separate analyses we also examined in depth the within-country trends of smoking and MS for two populations in which statistics on MS are readily available: Canada and Denmark.
RESULTS: We show that the gender ratio of MS is correlated with the gender ratio of smoking (r = 0.12, 95% CI: 0.02, 0.22; p = 0.02). This correlation supports an overall incidence rate ratio of 1.40 (95% CI: 1.02, 1.89) of MS for ever smokers as compared with never smokers. Furthermore, our within-country analyses of smoking and MS trends in Canada and Denmark show that, depending on model assumptions, smoking could explain 20 to 89% of the change in the female to male ratios of MS.
CONCLUSIONS/RELEVANCE: Our results are consistent with the hypothesis that smoking increases the risk of MS. Smoking trends might partially explain changes in the MS gender ratio.
http://www.abstracts2view.com/aan/view. ... 0L_S40.001
Phase II Double-Blind Controlled Clinical Trial with T-Cell Vaccination in Multiple Sclerosis
Rivka Abulafia-Lapid, Jerusalem, Israel, Massimo Filippi, Milan, Italy, Panayiota Petrou, Adi Vaknin-Dembinsky, Michal Mor, Oded Abramsky, Henry Atlan, Dimitrios Karussis, Jerusalem, Israel
OBJECTIVE: A phase I/II double-blind controlled clinical trial for the evaluation of the safety and efficacy of the T-cell vaccination in MS patients.
BACKGROUND: Previous studies showed that it is possible to modulate T-cell mediated autoimmunity by developing a specific, anti-idiotypic, anti-T cell immune response through vaccination with the relevant effector lymphocytes.
DESIGN/METHODS: 26 patients with definite MS diagnosis were enrolled to the study. All patients had severe progression/deterioration in the functional status (at least one degree in the EDSS) during the year prior to inclusion. The patients were randomized into two groups: 17 received the active treatment (TCV) and 9 received sham injection. Peripheral blood lymphocytes were obtained from each patient and cultured in the presence of 10 different myelin peptides. According to the proliferative response to those antigens, the reactive lymphocytes were expanded in vitro and an individually tailored vaccine was prepared. The cells were subsequently deactivated by irradiation and injected at days 1, 30 and 60. The one year follow up included monthly evaluations of the EDSS, ARR and MSFC score. Brain MRI was performed at baseline and year one, measuring the number and the volume of T2 lesions, T1 Gadolinium enhancing lesions and normalized brain volume.
RESULTS: The mean change in the EDSS score from baseline to year 1, was +0.39 in the placebo group and -0.44 in the TCV group (p<0.05). The mean annualized number of relapses in the TCV group was reduced from a mean of 0.82 during the year prior to the inclusion, to 0.06 after the TCV, whereas remained unchanged (1.0) in the placebo group. MRI parameters did not differ significantly between the 2 groups.
CONCLUSIONS/RELEVANCE: This controlled, blinded clinical trial with TCV in patients with progressive MS and shows the feasiblilty and safety of the procedure and provides some indications of clinical efficacy.
http://www.abstracts2view.com/aan/view. ... 0L_P06.134