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Saviola G.,Rheumatology and Rehabilitation Unit | Abdi-Ali L.,Rheumatology and Rehabilitation Unit | Campostrini L.,Laboratory and Clinical Biochemistry Unit | Sacco S.,Laboratory and Clinical Biochemistry Unit | And 4 more authors.
Modern Rheumatology | Year: 2012

We evaluated the efficacy of clodronate for treating active erosive osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7 days followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days followed by 200 mg daily for the next 11 months. In group A 21/24 patients completed the trial and obtained significant pain reduction (p<0.001) Dreiser's score (p = 0.012) and number of tender joints (p = 0.011). Strength of right (p = 0.04) and left (p = 0.016) hands, physician's global assessment (p ≤ 0.001), and patient's global assessment (p = 0.021) improved. In group B, 8/14 patients completed 12 months of the study, which showed the inefficacy of hydroxychloroquine and its lack of acceptance by patients (worsening pain and patient's global assessment). Therefore, enrolment was stopped. Differences between groups showed a pain decreasing trend for group A and a slightly increasing one for group B (p = 0.018). Physician and patient global assessments showed a strong increase in group A compared with group B (p<0.001). Clodronate is effective in erosive osteoarthritis; hydroxychloroquine seems to be ineffective. © Japan College of Rheumatology 2011. Source


Benucci M.,Rheumatology Unit | Saviola G.,Rheumatology and Rehabilitation Unit | Manfredi M.,Immunology and Allergology Laboratory Unit | Sarzi-Puttini P.,University of Milan | Atzeni F.,University of Milan
Biologics: Targets and Therapy | Year: 2013

Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are reports indicating that tumor necrosis factor (TNF) blockers may exert favorable but transient effects on the lipid profile, flow-mediated vasodilatation (FMD) of the brachial artery, and the common carotid intima-media thickness (ccIMT) in RA. We evaluated 38 RA patients (33 females and five males with a mean age of 66.7 ± 10.2 years) who were unresponsive to TNF blockers. The patients received one or more courses of two rituximab (RTX) 1000 mg infusions. Disease activity was evaluated at each visit. Investigations included erythrocyte sedimentation rate, C-reactive protein (CRP) levels, the 28-joint disease activity score (DAS28), DAS28CRP, the Health Assessment Questionnaire, the FMD percent change from baseline (FMD%), and the postnitroglycerine endothelium-independent vasodilatation. In comparison with the baseline, there was a significant improvement in clinical variables and acute-phase reactants 24 months after the start of RTX therapy. There was also a major improvement in FMD% (from baseline 5.24 ± 1.12 to 5.43 ± 1.16; P = -0.03) and a smaller change in the ccIMT (from baseline 0.69 ± 0.16 to 0.67 ± 0.12 mm P = 0.25). Univariate analysis showed that global health (P < 0.034) was associated with the improvement in FMD%. Multivariate models showed that GH (odds ratio [OR] 0.91; 95% CI: 0.99-0.83; P = 0.032), CD19+ cells (OR 1.024; 95% CI: 1.045-1.003; P = 0.025), IgM (OR 1.025; 95% CI: 1.045-1.004; P = 0.016), and interleukin (IL)-8 (OR 0.487; 95% CI: 0.899-0.264; P = 0.021) were statistically associated with the improvement of FMD%, and that IL-8 (OR 0.717; 95% CI: 0.926-0.555; P = 0.018) was also statistically associated with improvement of ccIMT The findings of the study confirm that RTX reduces the progression of accelerated atherosclerosis in patients with RA. They also show that improvement in CD19+ cells, IgM and GH after treatment are statistically associated with the improvement of FMD%, and that improvement in IL-8 levels after treatment is statistically associated with improved FMD% and with decrease in the ccIMT. © 2013 Benucci et al, publisher and licensee Dove Medical Press Ltd. Source


Benucci M.,Rheumatology Unit | Saviola G.,Rheumatology and Rehabilitation Unit | Manfredi M.,Immunology and Allergology Laboratory Unit | Sarzi-Puttini P.,University of Milan | Atzeni F.,University of Milan
Acta Biomedica | Year: 2012

Five anti-TNF agents, infliximab, adalimumab, etanercept, golimumab and certolizumab pegol are approved worldwide for the treatment of RA. Anti-TNF agents, bind to and neutralize soluble TNF-α, but exert different effects on transmembrane TNF-α-expressing cells (TNF-α-producing cells). Differences on affinity and avidity for soluble and transmembrane TNF-α were showed. Different activity on cells apoptosis, Complement-dependent cytotoxicity (CDC) antibody dependent cell-mediated cytotoxicity (ACDC) were described. Some dramatic changes in gene expression were seen with all the anti-TNFs. Reviewing the biology of transmembrane TNF-α and its interaction with anti-TNF agents will contribute to understanding the bases of differential clinical efficacy of these promising treatment modalities, (www.actabiomedica.it). © Mattioli 1885. Source


Benucci M.,Rheumatology Unit | Saviola G.,Rheumatology and Rehabilitation Unit | Baiardi P.,University of Pavia | Manfredi M.,Immunology and Allergology Laboratory Unit
Rheumatology International | Year: 2011

The cost-effectiveness of treatments that have the potential to change the "natural history" of a chronic progressive disease has to be evaluated over the long term. Cost-effectiveness estimates have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. This analysis focused on the use of Rituximab in treating patients with moderate to severe RA for whom at least one anti-TNFα blocking agent had failed. The aim of our study was to evaluate the cost-effectiveness in 32 patients with rheumatoid arthritis in therapy with a single infusion of Rituximab 1,000 mg given on days 1 and 15 of each month for 1 year. After 6 months of treatment, we observed for all 32 patients a total quality-adjusted life year (QALY) gained of 11,840 with an average of 0.37 QALY for a single patient, a treatment cost of €5,610 and a QALY/cost ICER (incremental cost-effectiveness ratio) of €15,114. After 1 year of treatment, we observed data for 28 patients with a total QALY gained of 11,480 with an average of 0.41 QALY for a single patient, a treatment cost of €9,690 and a QALY/cost ICER (incremental cost-effectiveness ratio) of €23,696. The benefit of using Rituximab is cost-effectiveness with a QALY/gained under the acceptable threshold of €50,000 in our observational study. These are important data for discussion from the economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice. © 2010 Springer-Verlag. Source


Buzzulini F.,Biomedical University of Rome | Rigon A.,Biomedical University of Rome | Soda P.,Biomedical University of Rome | Onofri L.,Biomedical University of Rome | And 4 more authors.
Arthritis Research and Therapy | Year: 2014

Introduction: In recent years, there has been an increased demand for computer-aided diagnosis (CAD) tools to support clinicians in the field of indirect immunofluorescence. To this aim, academic and industrial research is focusing on detecting antinuclear, anti-neutrophil, and anti-double-stranded (anti-dsDNA) antibodies. Within this framework, we present a CAD system for automatic analysis of dsDNA antibody images using a multi-step classification approach. The final classification of a well is based on the classification of all its images, and each image is classified on the basis of the labeling of its cells.Methods: We populated a database of 342 images-74 positive (21.6%) and 268 negative (78.4%)- belonging to 63 consecutive sera: 15 positive (23.8%) and 48 negative (76.2%). We assessed system performance by using k-fold cross-validation. Furthermore, we successfully validated the recognition system on 83 consecutive sera, collected by using different equipment in a referral center, counting 279 images: 92 positive (33.0%) and 187 negative (67.0%).Results: With respect to well classification, the system correctly classified 98.4% of wells (62 out of 63). Integrating information from multiple images of the same wells recovers the possible misclassifications that occurred at the previous steps (cell and image classification). This system, validated in a clinical routine fashion, provides recognition accuracy equal to 100%.Conclusion: The data obtained show that automation is a viable alternative for Crithidia luciliae immunofluorescence test analysis. © 2014 Buzzulini et al.; licensee BioMed Central Ltd. Source

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