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G Ferraccioli

Publications and source records attributed to G Ferraccioli.

At least 19 recordsLinked to original sources
PubMed2006

Consensus statement on the use of rituximab in patients with rheumatoid arthritis.

A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell-targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed2006

B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.

OBJECTIVES: To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation. METHODS: BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied. RESULTS: A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 +/- 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 +/- 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data. CONCLUSIONS: BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies.

Adult↗
PubMed2006

Pharmacogenetic of antirheumatic treatments: clinical implications.

Preliminary pharmacogenetic data suggest that germline genetic informations might be of value in individualizing disease-modifying antirheumatic drugs (DMARDs) therapy in various autoimmune chronic inflammatory diseases. Either DMARDs small molecules (DMARDs-SM) or DMARDs biological therapies (DMARDs-BT) might be selected for their lower toxicity or better efficacy based on single-nucleotide polymorphisms (SNPs) of genes governing the metabolism of drugs, or the response of immune cells to proinflammatory molecules, or the proinflammatory molecular activity of immune cells. Data available for one DMARDs-SM, methotrexate, suggest that a careful assessment of the SNPs of four enzymes involved in the folate metabolism allow one to construct a genetic index of toxicity (toxicogenetic index) that might be employed in daily practice to find the patient's most at risk. Only the full knowledge of the various gene polymorphisms controlling the phenotypic manifestations of the inflammatory-immunological milieu of each rheumatic disease will allow one to obtain the clear definition of a personalized medicine. Few different cytokine gene SNPs seem to be of importance in determining the susceptibility to diseases, or the aggressiveness of diseases. The role of genetics in affecting a possible clinical response to DMARDs-BT targeting specific inflammatory molecules or their receptors still has to be defined. However, the available data suggest that cytokine (and/or receptors) gene SNPs might indeed play a role in determining the biological effects, hence the clinical effectiveness of DMARDs-BT. Crucial to this aim will be the prospective analysis of clinical benefits and safety on the basis of the at baseline stratification of gene SNPs in each chronic inflammatory rheumatic disease before starting any new DMARDs-SM or DMARDs-BT.

Animals↗
PubMed2006

Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids.

OBJECTIVE: Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus nephritis and membranous idiopathic nephropathy and has proved effective in non-renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We investigated the possible efficacy and safety of rituximab in the treatment of cryoglobulinaemic nephritis. METHODS: Five patients with active, biopsy-proven, glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were treated with four weekly infusions of rituximab (375 mg/m2) in monotherapy, without steroids whenever possible. Rituximab was the first-line therapy in three cases. RESULTS: A rapid and sustained renal response was observed in all patients, in one of them without retreatment up to the last follow-up (month 21+). Renal biopsy was repeated after 6 months in one patient and histopathological improvement was documented. Three patients relapsed, at months +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with rituximab and again presented a rapid improvement in renal function. Maintenance therapy with rituximab was performed in two patients: nephritis remission was maintained in both. Fc-gamma receptor 3a (FcgammaRIIIa) genotype characterization was consistent with the clinical response observed. Rituximab also proved effective against other active MC manifestations, when present. No major side-effects occurred and steroids were not required in the follow-up. CONCLUSIONS: Rituximab may provide effective and safe therapy in type II MC-related glomerulonephritis, possibly as first-line therapy, avoiding steroids and hazardous immunosuppressive treatment.

Aged↗
PubMed2006

EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To formulate EULAR recommendations for the management of early arthritis. METHODS: In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. RESULTS: 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. CONCLUSIONS: 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.

Antirheumatic Agents↗
PubMed2006

Efficacy of cyclosporin-A in the long-term management of thrombocytopenia associated with systemic lupus erythematosus.

Thrombocytopenia frequently complicates systemic lupus erythematosus (SLE), and its long-term management may be problematic. Intravenous immunoglobulins and high doses of steroids are often effective as induction therapy, but thrombocytopenia frequently relapses during steroid tapering. Several immunosuppressive agents have been evaluated as induction or maintenance therapy in small series or in case reports. We describe six consecutive unselected SLE patients where cyclosporin-A (CyA) was effective and safe in the long-term management of thrombocytopenia and allowed steroid tapering. One relapse occurred during CyA reduction and responded to CyA dose adjustment. Steroids could be stopped in three out of six patients, and were maintained at very low doses in the remaining patients. CyA was stopped in one patient after one year of treatment, without relapse at month 11+ from discontinuation. No severe side effects were documented. Overall, these data suggest that CyA may prove to be an effective and safe therapeutic option for SLE-related thrombocytopenia.

Adrenal Cortex Hormones↗
PubMed2005

[Biologic therapy with anti-TNFα in rheumathoid arthritis].

OBJECTIVE: To evaluate the efficacy, the tolerability, and treatment survival of the association of anti-TNFα (Infliximab, Etanercept, Adalimumab) plus Methotrexate vs Methotrexate as monotherapy in patients with reumathoid arthritis (RA). METHODS: Review of published controlled randomized clinical studies on the association of anti-TNFα plus Methotrexate vs Methotrexate alone in patients with rheumathoid arthritis (RA). Results in terms of remission and progression of radiologic damage, and clinical response expressed in terms of ACR 50 or ACR 70 were reviewed in the different studies. RESULTS: In patients with RA the association of anti-TNFα plus Methotrexate led to a greater remission of radiologic damage and marked improvement of clinical response expressed as ACR 50 or ACR 70 compared to therapy with Methotrexate only. CONCLUSIONS: In the absence of controlled studies, review of the published studies showed that in RA patients the association of anti-TNFα plus Methotrexate is extremely more efficacious than therapy with Methotrexate only. Choice of the drug depends on the activity of the disease, the necessity of a fast response, the presence of side effects, the schedule of treatment and consequently the direct and indirect costs of the drug, and the easiness on supply and distribution.

Adalimumab↗
PubMed2003

[Neuropsychological tests, MRI and SPECT in the evaluation of CNS involvement in SLE].

OBJECTIVE: To assess the agreement between presence and location of central nervous system (CNS) structural damage and neuropsychological performance. METHODS: 21 unselected SLE patients underwent a 3 hours-long battery of neuropsychological tests sampling 15 cognitive functions. A neuropsychologist hypothesized for each SLE patient the most likely site of possible involvement, according to the neuropsychological performance. Patients underwent MRI scans within 6 months (3 months before or after) from neuropsychological tests and SPECT. RESULTS: 14 of the 21 SLE patients (66.6%) were impaired in at least 1 function; among these, 7 patients (33.3%) were mildly impaired and 7 (33.3%) had more than 3 functions impaired. 10 patients (48%) had abnormal MRI scan. Negative and positive agreements between neuropsychological performance and MRI scan were detected in 15 patients (71%; ?2 with Yates' correction 6.09, p 0.007, measure K for concordance 0.44, p 0.03). All the 6 negative agreements had no records of major neurologic or psychiatric events; among the 9 positive agreements, 6 presented previous major neurologic events and 2 minor neuropsychiatric symptoms. Among the subjects with disagreement, 1 was unimpaired with positive MRI and without neuropsychiatric symptoms, 5 were mildly impaired with negative MRI. CONCLUSIONS: A detailed neuropsychological evaluation along with MRI arose as a valid method to exclude or to identify, localize and clinically interpret CNS involvement in SLE. Disagreement between MRI and neuropsychological tests was detected mainly for mild cognitive impairment that might be the expression of functional (inflammatory or ischemic) processes.

Adult↗
PubMed2002

Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review.

Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr to supplement data from randomized controlled clinical trials over 6-24 months.

Antirheumatic Agents↗
PubMed2002

Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional combination therapy: direct and indirect evidence for a possible association with infections.

OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (ACA) (as well as of anti-DNA antibodies) in patients with rheumatoid arthritis treated with etanercept or combination therapy. METHODS: Eight patients treated with etanercept 25 mg twice weekly were studied for a period of 85 weeks. A control group of 39 patients with rheumatoid arthritis undergoing combination treatment (methotrexate (MTX) + cyclosporin A or MTX + chloroquine) were studied for the same period of time. The occurrence of anticardiolipin antibodies (ACA-IgG) and anti-DNA was examined, together with the possible occurrence of infections due to bacteria capable of inducing B cell activation. RESULTS: In 5/8 patients receiving etanercept an increase of ACA-IgG was seen, while anti-DNA became positive in 3/8 patients. A nasal or bronchial infection due to Staphylococcus aureus (Staph aureus) or a urinary tract infection due to E coli, occurred in all five cases. Antibiotic treatment produced a return to normal of ACA-IgG, and also of anti-DNA, in all cases except one. The infectious agent was eradicated in all subjects but one. In the control group Staph aureus was found in the nasal swab in 10/39 subjects; ACA-IgM (followed by ACA-IgG) appeared at the same time as infection occurred in 6/10, while no infection related to the increased ACA-IgM was recorded in the other four. CONCLUSIONS: Bacterial DNA, especially that enriched in CpG motifs, is a powerful immunostimulant that may, in some cases, lead to ACA or anti-DNA positivity, once tumour necrosis factor alpha is blocked. Eradication of the infections leads to a rapid decrease of ACA-IgG and of anti-DNA levels.

Adolescent↗
PubMed2002

[TNF- alpha gene polymorphisms in rheumatoid arthritis patients treated with anti-TNF-alpha agents: preliminary results].

OBJECTIVES: To study -238 and +489 TNF-alpha polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA). METHODS: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment length polymorphism procedure. Several clinical and serological parameters were also examined. RESULTS: Severe RA patients disclosed the -238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy. CONCLUSION: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus -238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

Adolescent↗
PubMed2001

A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis.

OBJECTIVE: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA). METHODS: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle. RESULTS: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction. CONCLUSION: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Adult↗
PubMed2000

Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia: clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma.

OBJECTIVE: Type II mixed cryoglobulinemia (type II MC) is often characterized by features of indolent B cell lymphoma (IBCL) found on pathologic examination of bone marrow, whereas the clinical evidence does not indicate a neoplastic disorder. To better address the issue of indolent malignant versus nonmalignant bone marrow lymphoproliferation underlying type II MC, molecular analyses of B cell clonality were performed in the present study, in conjunction with clinical and pathologic characterization. METHODS: Polymerase chain reaction DNA amplification of immunoglobulin heavy chain genes was performed in bone marrow biopsy specimens obtained from 15 selected patients with type II MC, all infected with hepatitis C virus. Five of them had also developed overt B cell lymphoma (OBCL) during followup. Bone marrow features were consistent with IBCL in 9 of the 15 patients (group 1) and with reactive lymphoplasmacytosis in 6 of the 15 (group 2). RESULTS: An oligoclonal B cell expansion was detected in 6 of 9 baseline bone marrow lesions from group 1 patients (biclonal or monoclonal expansion in the remaining 3 cases), and in 6 of 6 from group 2 patients. OBCL was always monoclonal. Selected lesions were analyzed by clonospecific hybridization and by cloning and sequence analysis in patients who had developed OBCL at followup. In 4 of 5 cases, OBCL did not originate from the dominant B cell clones that were overexpanded in the putative neoplastic baseline bone marrow lesions. OBCL clones showed significant homology with rheumatoid factor database sequences. CONCLUSION: Based on the present results, as well as on evidence from previous studies of liver lesions, oligoclonal non-neoplastic B cell proliferation in the course of chronic infection-related inflammation appears to be the key feature of type II MC. Of note, molecular evidence from target tissues supports the clinical findings both at the time of type II MC diagnosis and in cases of OBCL complication. Bone marrow pathologic findings resembling those of IBCL should thus be considered in the light of clinical and molecular evidence.

Adult↗
PubMed2000

Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: viral detection in gastric low-grade lymphoma associated with autoimmune disease and in chronic gastritis.

The hepatitis C virus (HCV) has been linked to B-cell lymphoproliferation and autoimmunity, and has been localized in several tissues. The clinical observation of an HCV-infected patient with Sjögren's syndrome (SS) and Helicobacter pylori (HP) positive gastric low-grade B-cell non-Hodgkin's lymphoma (NHL), which did not regress after HP eradication, led us to investigate the possible localization of HVC in the gastric microenvironment. HCV genome and antigens were searched in gastric biopsy specimens from the previously mentioned case, as well as from 9 additional HCV-infected patients (8 with chronic gastritis and 1 with gastric low-grade B-cell NHL). HCV-specific polymerase chain reaction (PCR) and immunohistochemistry procedures were used. The gastric B-cell NHL from the patient with SS was characterized by molecular analyses of B-cell clonality. HCV RNA was detected in both the gastric low-grade B-cell NHL and in 3 out of 6 gastric samples from the remaining cases. HCV antigens were detected in the residual glandular cells within the gastric B-cell NHL lesions, in glandular cells from 2 of the 3 additional gastric lesions that were HCV positive by PCR, and in 1 additional chronic gastritis sample in which HCV-RNA studies could not be performed. By molecular analyses, of immunoglobulin genes, the B-cell NHL from the patient with SS was confirmed to be a primary gastric lymphoma, subjected to ongoing antigenic stimulation and showing a significant similarity with rheumatoid factor (RF) and anti-HCV- antibody sequences. Our results show that HCV can localize in the gastric mucosa.

Aged↗
PubMed2000

Cyclosporine-A plus steroids versus steroids alone in the 12-month treatment of systemic lupus erythematosus.

The positive results obtained with cyclosporine-A both in an experimental model and in selected patients with advanced systemic lupus erythematosus support the hypothesis that the drug could be used as a steroid sparer in the earliest stages of active disease. To determine the 12-month clinical efficacy (disease control and steroid sparing), safety, and tolerability of low-dose cyclosporine-A plus steroids versus steroids alone, we designed a multicenter, open, prospective, randomized, pilot study, controlled for parallel groups. The patients were then followed up to month 24. A total of 18 consenting patients with recently diagnosed systemic lupus erythematosus of moderate severity indicated for the use of steroids in acute boluses and subsequently per os were enrolled at two university hospital medical centers. The protocol was based on three 1-g boluses of 6-methylprednisolone followed by cyclosporine-A (<5 mg/kg per day) plus prednisone 0.5-1 mg/kg per day per os, reduced by 5 mg/day every 2 weeks following clinical remission, versus the same doses of oral prednisone alone. The efficacy evaluation was based on a four-point scale (from absent/none to severe) for signs and symptoms of systemic lupus erythematosus and immunoserological parameters. The disease activity index and cumulative prednisone dose per patient were analyzed. Any adverse events were reported. All patients showed a reduction in disease activity index within the 1st month. The results were significantly better in the group with cyclosporine-A plus prednisone throughout month 12 (baseline and 12-month disease activity indexes: 21.3+/-8.6 and 5.0+/-2.5 versus 20.4+/-7.1 and 8.8+/-6.0 in the prednisone group, P<0.05). The 12-month cumulative mean dose of prednisone was significantly lower in the group with both cyclosporine-A plus prednisone (179.4+/-40.1 versus 231.8+/-97.1 mg/kg, P<0.005). No unusual adverse events related to the study drugs have been reported. In particular, renal function and blood pressure monitoring revealed no significant changes from mean baseline values in either group. No disease flares were reported in the group treated with cyclosporine-A plus prednisone during the 12- to 24-month period. Thus cyclosporine-A represents a useful corticosteroid sparer in the maintenance of clinical remission in patients with an early-stage, active systemic lupus erythematosus.

Adolescent↗