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Background and purpose: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. Methods: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double‐blind, multicentre, non‐inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non‐inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non‐inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium‐enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. Results: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, −0.26 (−0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium‐enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. Conclusions: A lesser high‐dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response. [ABSTRACT FROM AUTHOR]

Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti‐inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti‐inflammatory disease‐modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease‐modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention‐to‐treat and an as‐treated approach in paired, pairwise‐censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on‐study pairwise‐censored follow‐up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3‐month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease‐modifying agents suggests that these therapies have no substantial effect on short‐ to medium‐term disability outcomes in PPMS. [ABSTRACT FROM AUTHOR]

Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP.Trial registration: clinicaltrials.gov identifier: NCT00753792 [ABSTRACT FROM AUTHOR]

The article focuses on the study which compares the clinical and radiologic efficacy of intravenous methylprednisolone (ivMP) against oral methylprednisolone (oMP) at equivalent high doses for multiple sclerosis (MS) relapse. It states the main outcome of noninferiority at four weeks for improved expanded disability status scale (EDSS) score. It mentions that oMP is not inferior to ivMP in reducing the score of EDSS.

Background: The identification of major immunogenic peptides in multiple sclerosis (MS) is of great importance for the development of antigen-specific therapies. Cellular reactivity against a selected mix of seven myelin peptides was evaluated in vitro. The evolution of this reactivity over time and its correlation with clinical variables was also analysed. Material and methods: Forty-two patients with MS, 15 with other demyelinating diseases and 40 healthy donors (HD) were studied. Cell proliferation was measured by 3[H] thymidine incorporation into samples obtained at 0, 3, 6 and 12 months of MS patient follow-up. Results: A positive reaction to the peptide mix was detected in 31 of the 42 patients (74%), 12 of the 40 HD (30%) and 6 of the 15 (40%) patients with other demyelinating diseases. Patients with positive proliferation had greater disability (EDSS score, 3 [1-5.5] vs. 1.0[1-2], P = 0.021), higher number of relapses (7 ± 4.1 vs. 3 ± 1.2, P < 0.001) and shorter time since the last relapse (9 ± 7.5 vs. 32 ± 12.3 months, P = 0.036). After 12 months of follow-up, cell reactivity was maintained in 33 patients (78%). Conclusion: A high percentage of patients exhibit a significant and maintained reactivity to myelin peptides over time. Therefore, this mix may be useful as a source of antigen in the development of protocols aimed at inducing specific tolerance in MS. [ABSTRACT FROM AUTHOR]

The post-marketing international Global Adherence Project investigated adherence to disease-modifying therapy for relapsing-remitting multiple sclerosis. We report adherence data from the first 2 years in the Spanish subset of patients (n = 254 at baseline). The overall adherence rate was 85.4%. Patients taking intramuscular (IM) interferon-β (IFNβ)-1a were significantly more adherent (96.4%) compared with patients taking subcutaneous (SC) IFNβ-1a 22 μg (79.1%; p = 0.0064), SC IFNβ-1a 44 μg (79.6%; p = 0.0064) and glatiramer acetate (82.7%; p = 0.0184). At year 1 (n = 142), the overall adherence rate was 86.6%. Patients on IM IFNβ-1a were significantly more adherent than patients on SC IFNβ-1a 22 μg (93.9 vs. 66.7%; p = 0.0251). At year 2 (n = 131), the overall adherence rate was 82% (87.5% for IM IFNβ-1a, 80.0% for SC IFNβ-1a 22 μg, 77.8% for SC IFNβ-1a 44 μg, 85.2% for IFNβ-1b, and 80.0% for glatiramer acetate). In conclusion, adherence remained high among all disease-modifying therapies over the first 2 years of the study and was significantly higher for IM IFNβ-1a, at visit 1, compared with SC IFNβ-1a. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. This was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNβ-1a), subcutaneous IFNβ-1a, IFNβ-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. Two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients ( n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life ( P < 0.05) and fewer neuropsychological issues ( P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease ( P < 0.001) and shorter duration of therapy ( P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. Identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs. [ABSTRACT FROM AUTHOR]

Background: The use of tolerogenic DCs is a promising therapeutic strategy for transplantation and autoimmune disorders. Immunomodulatory DCs are primarily generated from monocytes (MDDCs) for in vitro experiments following protocols that fail to fulfil the strict regulatory rules of clinically applicable products. Here, we compared the efficacy of three different tolerance-inducing agents, dexamethasone, rapamycin and vitamin D3, on DC biology using GMP (Good Manufacturing Practice) or clinical grade reagents with the aim of defining their use for human cell therapy.Methods: Tolerogenic MDDCs were generated by adding tolerogenic agents prior to the induction of maturation using TNF-α, IL-β and PGE2. We evaluated the effects of each agent on viability, efficiency of differentiation, phenotype, cytokine secretion and stability, the stimulatory capacity of tol-DCs and the T-cell profiles induced.Results: Differences relevant to therapeutic applicability were observed with the cellular products that were obtained. VitD3-induced tol-DCs exhibited a slightly reduced viability and yield compared to Dexa-and Rapa-tol-DCs. Phenotypically, while Dexa-and VitD3-tol-DCs were similar to immature DCs, Rapa-tol-DCs were not distinguishable from mature DCs. In addition, only Dexa-and moderately VitD3-tol-DCs exhibited IL-10 production. Interestingly, in all cases, the cytokine secretion profiles of tol-DCs were not modified by a subsequent TLR stimulation with LPS, indicating that all products had stable phenotypes. Functionally, clearly reduced alloantigen T cell proliferation was induced by tol-DCs obtained using any of these agent. Also, total interferon-gamma (IFN-γ) secretion by T cells stimulated with allogeneic tol-DCs was reduced in all three cases, but only T cells co-cultured with Rapa-tol-DCs showed impaired intracellular IFN-γ production. In addition, Rapa-DCs promoted CD4+ CD127 low/negative CD25high and Foxp3+ T cells.Conclusions: Our results demonstrate contrasting influences of different clinical-grade pharmacological agents on human tol-DC generation. This should be taken into account for decisions on the use of a specific agent for the appropriate cellular therapy in the context of a particular disease. [ABSTRACT FROM AUTHOR]