Biomedical subjects

Massimiliano Calabrese

Publications and source records attributed to Massimiliano Calabrese.

4 recordsLinked to original sources

PubMed2006

Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis: a comparative study.

Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one or more EDSS points in the prior two years were selected to receive either cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4 years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2 years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS patients were treated for two years with clinical evaluation (relapse rate, disability progression) every three months and radiological imaging (conventional magnetic resonance imaging) before therapy initiation and at the end of the first and second years of therapy. Safety profile and costs of the two therapeutic protocols were also analysed. In terms of clinical and radiological measures the drugs exerted a quite identical effect on both, and produced a significant reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01). Subgroups of mitoxantrone- and cyclophosphamide-responding patients were identified (14/25 and 17/25, respectively) and were characterized by a significantly shorter duration of the secondary progressive phase of the disease. In these subgroups, the improvement in the EDSS score at the end of therapy was highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of both drugs were acceptable; however, the Cy-based therapy protocol was significantly less expensive. We conclude that Cy should be considered as a therapeutic option in rapidly deteriorating SPMS patients.

Adult↗

PubMed2006

Multiple sclerosis and autoimmune diseases: epidemiology and HLA-DR association in North-east Italy.

An autoimmune background is thought to characterize the families of multiple sclerosis (MS) patients, but disease patterns and HLA-DR association seem to vary considerably among different ethnic groups. We investigated the prevalence of autoimmune diseases in 245 MS patients and 245 age- and sex-matched normal controls (NC), originating from and living in North-east Italy, and their first degree relatives, using a case-control method. Further, HLA-DRB1 expression was analysed in MS and NC. The following significant findings were observed: 1) a significant excess of autoimmunity in first-degree relatives of MS patients (p = 0.000), 2) an association of MS with Type 1 diabetes mellitus (T1DM) (p = 0.02), 3) an increase in DR4 expression (namely DRB1*0401) in MS patients from families with multiple autoimmune pathology compared with reference MS patients (p=0.02) and NC (p=0.01). We conclude that the risk of autoimmune disease is higher in first-degree relatives of MS patients and that disease association and HLA-DR expression in North-east Italy differs from other geographic regions of Europe.

Adolescent↗

PubMed2006

Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients.

To investigate whether peripheral immune abnormalities are associated with brain inflammation in multiple sclerosis, and whether differences in MRI activity are paralleled by changes in leukocyte composition, we conducted a prospective longitudinal study in patients at their clinical onset. Twenty patients presenting a first inflammatory event in the central nervous system suggestive of multiple sclerosis underwent, every 45 days for one year, immunophenotyping of 98 blood cell subsets together with brain MRI and clinical evaluation. Six patients showed intense MRI activity, six patients did not display MRI activity, while the remaining 8 patients had low (i.e. intermediate) MRI activity during the follow-up. Our results show that MRI-active and MRI-inactive patients display significant differences in ten lymphocyte subsets. Among these, there are both effector (CCR7-CD45RA-CD4+ alphabeta T cells, CCR5+ gammadelta T cells) and regulatory (DN CD28+ alphabeta T cells and CD25+CD8+ alphabeta T cells) lymphocytes pertaining to the innate and the acquired arms of the immune system. Moreover, these differences were, upon employment of a class prediction procedure based on "support vector machines" algorithm utilizing leave-one-out cross validation procedures, able to correctly assign patients to their respective MRI activity group. All 6 MRI-active and 6 MRI-inactive patients were correctly classified, and, upon application of a class prediction model in an unsupervised manner to the 8 patients with intermediate MRI activity, 6 were predicted as MRI-active and 2 as MRI-inactive patients. Also, when the mean values of the first three time points (T0, T1 and T2) were used for the prediction of all patients, the selected lymphocyte subsets correctly classified 90% of patients. Sensitivity was 91.7% and specificity was 87.5%. These results provide evidence showing that brain inflammation in multiple sclerosis is associated with distinct changes in peripheral lymphocyte subsets, and raise the possibility that the identified subsets may, after adequate validation, assist in the prediction of MRI activity in the early stages of multiple sclerosis.

Adult↗

PubMed2004

The clinical impact of interferon beta antibodies in relapsing-remitting MS.

We analysed the kinetics and clinical impact of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to three interferon beta (IFNbeta) products in patients with relapsing-remitting MS (RRMS). Patients with RRMS received IFNbeta-1b 8 MIU subcutaneously (SC) every other day, intramuscular (IM) IFNbeta-1a 30 mcg once weekly, or SC IFNbeta-1a 22 mcg three times weekly for up to 4 years. The changes of BAbs and IFNbeta were measured using enzyme-linked immunosorbent assay (ELISA), and positive BAb samples were then analysed for neutralizing activity using an antiviral cytopathic effect assay. Patients were considered BAb+ if they had a positive sample with an optical density (OD)>mean + 3SD of the OD of the control sample; high BAb titers were defined as >1:500. Patients were considered NAb+ if they had titers > or =20 LU/mL, with high NAb titers defined as >1:100. The impact of BAbs and NAbs on relapses and Expanded Disability Status Scale (EDSS) score also was evaluated. Thirty patients were enrolled in each treatment group. Over the course of the study, 83% of patients developed BAbs to IFNbeta-1b, 13% to IM IFNbeta-1a, and 47 % to SC IFNbeta-1a. Forty percent of patients developed NAbs to IFNbeta-1b, 6.7% to IM IFNbeta-1a, and 26.7% to SC IFNbeta-1a. Of 22 NAb+ patients, 10 patients (45.5%) demonstrated high titers of both NAbs and BAbs (20% IFNbeta-1b, 3.3% IM IFNbeta-1a, 10% SC IFNbeta-1a). The relapse rate significantly increased after the appearance of high NAb titers (p=0.03); however, an even higher significance level (p<0.001) was observed in patients with high titers of both NAbs and BAbs. In 10 patients with high titers of both NAbs and BAbs, an increase in mean EDSS score from 2.2 +/- 0.8 at baseline to 3.6 +/- 1.2 at year 2 (p<0.01) was observed. NAb-negative patients showed no significant change in EDSS score at year 2. These findings demonstrate that high titers of both BAbs and NAbs reduce the clinical efficacy of IFNbeta in patients with RRMS, which is important for the long-term efficacy of these drugs.

Adolescent↗