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Background: Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.Objective: To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.Methods: We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.Results: 195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).Conclusion: Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-β administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-β treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or -non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-β in naïve MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-β treatment are more likely to be non-responders to this therapy. [ABSTRACT FROM AUTHOR]

Adherence to an immunomodulatory therapy still needs to be improved in MS patients. We analyzed the data of 396 MS patients of 40 German MS outpatient centers who had stopped an ongoing immunomodulatory treatment. Items analyzed were among others adherence data, reasons for the interruption and willingness to start a new therapy. It became obvious that 74.6 % of the patients made the decision to withdraw from therapy on their own. The most commonly mentioned reasons for the withdrawal were proven or putative lack of efficacy (51.4 %), side effects (58.1 %), and complaints of fatigue and depression. There was no difference concerning sex, duration of the treatment and medication taken. The expectations correlated with the empathy of the treating physician and the setting with MS nurses taking care of the patient. A total of 199 patients (51.8 % of the females, 48.9 % of the males) wanted to restart another IMT. Reasons for not wanting to restart were lack of conviction that a therapy may influence the disease (29.4 %), fear of injection (18.7 %), fear of bringing the disease to mind regularly (17.9 %) and doubt about the diagnosis (11.2 %). The results suggest that adherence is most effectively promoted by cultivating an appropriate and individual therapeutic setting for each MS patient on a medical, organizational and last but not least psychological level. [ABSTRACT FROM AUTHOR]

Various types of experimental autoimmune encephalomyelitis (EAE) reflect some of the pathogenetic, clinical, and therapeutic features of the different forms of multiple sclerosis (MS), thereby, providing some, albeit limited, insight into the molecular and cellular basis of the human disease. Specific questions of MS therapy including the search for new therapeutic targets and strategies and their validation require investigations in different available EAE models. A survey is given of experimental therapeutic approaches that are currently under study with the most promising examples of monoclonal antibodies, gene therapy, stem cell transplantation and orally applied small molecular weight disease-modifying drugs. Reasons for therapy failure and adverse side-effects of some experimental trials are discussed. Precaution is advised, if results of new experimental approaches are translated into clinical practice. [ABSTRACT FROM AUTHOR]