Immunomodulatory therapies delay disease progression in multiple sclerosis.

BACKGROUND: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs). OBJECTIVE: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies. METHODS: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression. Patients were stratified on the basis of the risk score BREMS (Bayesian risk estimate for multiple sclerosis), which is able to predict the unfavourable long-term evolution of MS at an early stage. RESULTS: We analysed data from 1178 patients with a relapsing form of multiple sclerosis at onset and at least 10 years of disease duration, treated (59%) or untreated with DMDs. The risk of secondary progression was significantly lower in patients treated with DMDs, regardless of the initial prognosis predicted by BREMS. CONCLUSIONS: DMDs significantly reduce the risk of multiple sclerosis progression both in patients with initial high-risk and patients with initial low-risk. These findings reinforce the role of DMDs in modifying the natural course of the disease, suggesting that they have a positive effect not only on the inflammatory but also on the neurodegenerative process. The study also confirms the capability of the BREMS score to predict MS evolution.

Duloxetine is effective in treating depression in multiple sclerosis patients: an open-label multicenter study.

OBJECTIVES: Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for its therapeutic efficacy, safety, and tolerability in the treatment of depression in patients with multiple sclerosis (MS). Lifetime depression prevalence approaches 50% in MS patients. The aim of the study was to assess the safety and efficacy of duloxetine for treatment of depression in MS patients. METHODS: An open-label study evaluated the efficacy of 12 weeks of duloxetine administration (maximal dose = 60 mg/d) in MS patients with clinical depression. The Beck scale score variation after 4 (T1) and 12 (T2) weeks of treatment was used for the primary outcome measurement, whereas secondary outcome was measured using the Modified Fatigue Impact Scale. Safety was evaluated by recording treatment-related adverse events, monitoring vital signs, and recording frequency and reasons for interruption or discontinuation of treatment. RESULTS: Seventy-five patients were enrolled in the study. Sixty-three patients completed the study by continuing duloxetine treatment for 12 weeks (T2). Twelve subjects dropped out of the study because of adverse effects or noncompliance. Nausea was the most common adverse event reported. A significant reduction in the Beck Depression Inventory and Modified Fatigue Impact Scale scores, after both 4 and 12 weeks of therapy, was observed. CONCLUSIONS: The results suggest that duloxetine is well tolerated, safe, and effective in reducing depression and fatigue in MS patients.

Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects.

BACKGROUND: The association of HLA A*02 with multiple sclerosis (MS) was recently confirmed by the authors, and it was observed that the combined presence of HLA Cw*05 significantly enhanced (threefold) the protective effect of HLA A*02. OBJECTIVES AND METHODS: Since A*02-Cw*05 is carried by two HLA extended haplotypes characterised by the B*4402 and B*1801 alleles, respectively, the association analysis was extended to HLA B*44 and B*18 in an Italian sample (1445 MS cases and 973 controls) and these associations were verified in a UK cohort (721 MS cases, 408 controls and 480 family trios). RESULTS: A strong protective effect, independent of DR15, of the A*02-Cw*05 combination carrying B*44 (OR 0.27, p=3.3×10(-5)) was seen in the Italian samples and confirmed in UK family trios (OR 0.33, p=5.5×10(-4)) and in a combined cohort of UK families and case-controls (OR 0.53, p=0.044). This protective effect was significantly stronger than that mediated by A*02 alone. Logistic regression showed that A*02-Cw*05 maintained a significant protection when adjusted for B alleles (Italy: OR 0.38, p=6.5×10(-7); UK: OR 0.60, p=0.0029), indicating that it was not secondary to linkage disequilibrium with B*44. Different from A*02, the other HLA class I tested markers individually showed no significant (Cw*05, B*18) or a modest (B*44) protection when adjusted for the remaining markers. CONCLUSIONS: This study identified at least two independent protective effects which are tagged by A*02-Cw*05 and A*02, respectively. Further studies are needed to elucidate whether this protective effect is due to the presence of an unanalysed factor characterising the HLA extended haplotype(s) carrying A*02 and Cw*05 or to a direct interaction between these alleles.

Inverse relationship between multiple sclerosis and allergic respiratory diseases.

Th1 up-regulation seems to favour autoimmunity, while Th2 up-regulation seems to favour humoral immunity. Accordingly, subjects affected by atopic diseases (such as allergic respiratory diseases, ARDs) should be less prone to autoimmune diseases (such as multiple sclerosis, MS), and vice versa. The recent identification of Th17 cells, which seem to favour the development of both autoimmunity and allergy, led to the revision of the classic Th1/Th2 paradigm. We studied 200 MS patients and 200 controls to analyze the relationships between ARDs and MS. MS patients had less probability to suffer from ARDs (OR = 0.30, p < 0.001) and allergic rhinitis (OR = 0.25, p < 0.001), after adjusting for environmental factors. MS tended to be less severe when associated to ARDs. Our findings add some elements for the comprehension of immune mechanisms involved in MS pathogenesis and suggest to analyze other MS cohorts, in order to evaluate if MS patients affected by allergic diseases show particular clinical findings.