Search

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA (p < 0.001). The drug discontinuation rate was 5.5% with a mean of 6.8 months (range 2-10 months), and it was due to lack of efficacy, adverse events, and lost to follow-up. Nine patients (6.2%) reported the onset of mild infections resolved with antimicrobial specific oral regimen without therapy interruption. TNF-α blockers are effective in the achievement of a low disease status and safe in elderly patients with PsA. Therefore, age should not be considered a limitation to their use.

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-F + CD161 + IL23 + CD4 + T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-F + IL23 + - IL17A-F + CD161 + - and IL17A-F + CD161 + IL23 + CD4 + T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4 + T and CD4 + IL23 + T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA.

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA.

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.

Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis., (Copyright 2010 Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was the evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA)., Methods: Systemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105., Results: At baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3)., Conclusions: Synovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

Objective: To determine the effect of tumour necrosis factor alpha (TNFalpha) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring., Methods: 27 knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed before receiving treatment and at 3 and 12 months' follow up. Time dependent clinical changes in disease activity were monitored by C reactive protein, erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by ultrasonographic and power Doppler indices for grey scale synovial thickening and for distinct intrasynovial vessel power Doppler flow configurations (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)). Interobserver and intraobserver variability of grey scale and power Doppler ultrasonographic was evaluated. Response to treatment was assessed by analysis of variance for repeated measures on clinical and ultrasonographic variables., Results: Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI, and GHS (p<0.001), was sustained at 12 months when it was accompanied by reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic variables between either the rheumatoid or the psoriatic KJS groups., Conclusion: Grey scale and power Doppler ultrasonography are reliable measures of long term change in rheumatoid and psoriatic KJS disease activity in response to anti-TNFalpha treatment with etanercept.

Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA). In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX); the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20), compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ) were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN) and the Total modified Sharp-Genant score (a combination of erosion and JSN) in all treatment groups (30,75 and 150mg/day). The clinical benefits of treatment with daily subcutaneous injections of IL-1ra in active RA patients were maintained for up to 48 weeks. IL-1ra, a selective inhibitor of the IL-1 pathway, represents an important new biologic approach to treating patients with RA, that significantly reduces clinical signs and symptoms of the disease and joint destruction and has proved safe and well tolerated also in combination with other DMARDs and concomitant medications.

Objective: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy., Methods: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated., Results: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%., Conclusion: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.

Objective: To evaluate the diagnostic utility of standard arthroscopy supported by a computerized image analysis system; and to examine and quantify the macroscopic appearance of blood vessels in selected anatomical areas, comparing 2 groups of patients with PsA and RA with refractory knee joint synovitis (KJS) for vascular marking (VM) features and VM scores, as well as for the relationship between respective VM scores and local and systemic KJS disease activity indices., Methods: Standard arthroscopy was carried out on 39 knees (20 PsA, 19 RA). Videorecordings of the examination were reanalyzed using a computer image analysis system and software. The appearance of vascular markings was assessed and separately scored for the areas of surface synovium (capsular, CVM), villous proliferation (villous, VVM), and synovium adherent to cartilage (pannus, PVM). Indices of systemic (erythrocyte sedimentation rate, ESR) and local KJS disease activity (clinical index) were obtained before arthroscopy. The morphology and scores of the distinct VM were compared between PsA and RA groups, as was the relationship between respective VM scores and ESR and KJS clinical indices., Results: Distinctive VM features were observed for PsA and RA KJS in each separate synovial architecture examined. VVM and CVM scores were significantly correlated with each other in PsA knees, and were significantly higher in PsA compared with RA. In both diseases, VVM and CVM scores were not related to KJS duration or activity or to ESR values, but in RA they were directly correlated with KJS activity. Moreover, the VVM capillary feature "meandering with tight convolutions," considered unique to psoriatic skin, was observed in the synovium of 13 PsA (65%) and one RA KJS (5.5%). The mean KJS duration of the PsA group with typical VVM was significantly lower than the group without VVM (2.6 +/- 1.77 vs 9.4 +/- 8.28 yrs)., Conclusion: Our macroscopic observations of distinct changes in VM expression in selected anatomical areas of PsA and RA KJS suggest possible pathogenetic differences between the 2 diseases. The typical morphology and higher intensity of villous vascularization, in both early and chronic disease, and the different clinical relevance of VVM scores in PsA compared with RA KJS support the potential use of vascular markings as reliable outcome measures of the PsA process in KJS.