Predictors of disease activity in gout: a 12-month analysis of the ATTACk (Achieving improvement in the management of crystal-induced arthritis) multicentre cohort study.

OBJECTIVES: Gout treatment is largely suboptimal in clinical practice. We aimed to assess the predictors of disease-activity at 12 months in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre-cohort study. Only patients with clinical diagnosis of gout were eligible. Disease-activity was evaluated by the Patient Acceptable Symptom State (PASS) on a visual analogue scale (VAS, 0=unsatisfactory, 100=satisfactory) at 0 (T0) and 12 months (T12), and the composite score called Gout Activity Score (GAS) calculated on the number of arthritic attacks (flare count), serum uric acid (sUA), cumulative number of tophi, VAS (T12), PtGA (T12). Multivariate linear regression model was performed to assess predictors of gout disease-activity at T12 with PASS and GAS as outcomes. RESULTS: 201 patients had gout (diagnosis on synovial fluid in 45%, tophi in 26%, mean sUA 7.4±1.9 mg/L, 85% with urate-lowering therapy (ULT) in progress/initiated at T0); mean age 63±13 years, 88% men, median (interquartile range) disease duration 2.9 years (0.7-9.4). Follow-up visits were performed in 113 (56%) patients at T12. Mean PASS observed at T0 and at T12 were 38±27 and 74±23, respectively, whereas GAS at T12 was 10±8. A significant association was observed between the presence of tophi and PASS at T12 (-15.3, 95% CI -25.5, -5.2; p=0.003) and GAS at T12 (+4.0, 95% CI 0.6,7.4; p=0.02), adjusted for age, sex, disease duration, sUA <6 mg/dL, tender joint count, PASS at T0, ULT). CONCLUSIONS: The baseline presence of tophi may predict high disease-activity at T12, thus worsening GAS and patients' pain perception.

Analysis of rheumatoid- vs psoriatic arthritis synovial fluid reveals differential macrophage (CCR2) and T helper subsets (STAT3/4 and FOXP3) activation.

OBJECTIVE: In psoriatic arthritis (PsA) and rheumatoid arthritis (RA), inflammatory responses are characterized by increased production of pro-inflammatory molecules secreted by various immune cells. The main objectives of our study were: i) to measure levels of pro- and anti-inflammatory cyto-chemokines and soluble factors expressed in both PsA and RA SF; ii) to characterize the phenotype of infiltrated leuko-lymphocytes and; iii) to identify specific synovial biomarkers for both diseases. Notably, Synovial Fluid (SF) samples obtained from PsA and RA populations were compared with SF samples collected from clinically active osteoarthritis (OA) joints. METHODS: SF samples were collected from clinically active knee arthritis of PsA, RA and OA patients and assayed for cyto-chemokines profile and macrophage and T helper subsets markers and transcriptional factors by Elisa Spot and western blot. RESULTS: our study revealed that modulation of CCL-2, G-CSF, IL-1ß and TNF-α is peculiar and specific to RA synovial fluid, whereas we detected more significant levels of ICAM-1, IL-2, IL-6, IL-17A, C5a and CXCL-9/12 in PsA compared to RA patients. We also found that CCR2 expression appeared to be significantly upmodulated in PsA and, even more, in RA group, as well as the expression of specific Th and Treg transcriptional factors as STAT3/4 and FOXP3. CONCLUSION: Even though this study has several limitations, we identified a heterogenous scenario of peculiar molecular pathway and soluble mediators' production that characterize PsA and RA SF that may be useful in understanding the complex pattern of macrophages and lymphocytes infiltration in both pathologies and, potentially, pave the way for personalized precision therapies.

Impact of disease duration and gender on the sensitivity and specificity of 2015 ACR/EULAR classification criteria for gout. Cross-sectional results from an Italian multicentric study on the management of crystal-induced arthritis (ATTACk).

OBJECTIVES: We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. RESULTS: Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67-86) and 98% (95%CI, 87-100), respectively; only clinical criteria yielded 70% (95%CI, 59-80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (<2 years), the sensitivity dropped to 58% (95%CI, 39-75), while the specificity was 100% (95%CI, 85-100). CONCLUSIONS: The ACR/EULAR criteria showed good performance in patients presenting with acute arthritis; changes were observed when a subset of criteria were used, especially in early-stage disease.

Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.

OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA. RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.

OBJECTIVE: The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS). METHODS: In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses. RESULTS: The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved). CONCLUSION: The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

Basic calcium phosphate and pyrophosphate crystals in early and late osteoarthritis: relationship with clinical indices and inflammation.

The current study aimed to investigate the association of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in synovial fluid (SF) of patients with osteoarthritis (OA) with disease severity, clinical symptoms, and synovial inflammation. One-hundred-and-ten patients with knee OA completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) self-assessment questionnaire, the Lequesne algofunctional index survey, and the visual analogic scale forms; they also underwent power Doppler ultrasonography (PDUS) to assess synovial inflammation. Scanning electron microscopy (SEM) was used to detect SF crystals. SEM analyses uncovered CPP crystals in 26 patients (23.6%), BCP crystals in 24 patients (21.8%), and both types of crystals in 7 patients (6.3%). Categorizing patients according to SF crystal type, a strong association between BCP crystal presence, and higher WOMAC and Lequesne index scores has been uncovered. Classifying our patients according the severity Kellgre-Lawrence score, we found that the prevalence of CPP alone (27.8%) or in combination with BCP (11.1%) was higher in the late stage group with respect to the early one (CPP 21.6% and CPP + BCP 4.1%, respectively). The prevalence of BCP crystals alone was, instead, higher in the early (23%) with respect to the late group (19.4%). No association between the presence of crystals and the radiographic scores has been observed. Considering the growing evidence supporting a role of low-grade inflammation in OA pathogenesis, the results of this study suggest a role for calcium crystals in the development of the disease.

Work productivity is associated with disease activity and functional ability in Italian patients with early axial spondyloarthritis: an observational study from the SPACE cohort.

BACKGROUND: Spondyloarthritis often affects young people, typically in their working years. The aim of our study was to investigate work productivity and its relationship with disease activity and physical functioning in Italian patients with axial spondyloarthritis (axSpA) with chronic back pain (CBP) for ≥3 months and ≤2 years, and onset < 45 years of age. METHODS: Baseline absenteeism, presenteeism, work productivity loss (assessed by the Work Productivity and Activity Impairment questionnaire (WPAI)), and disease activity (assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)/Ankylosing Spondylitis Disease Activity Score (ASDAS)) and functional ability (assessed by the Bath Ankylosing Spondylitis Disease Functional Index (BASFI)) of patients with axSpA (rheumatologist's diagnosis) included in the Italian section of the Spondyloarthritis Caught Early (SPACE) cohort were collected. Multivariate linear regression analysis was used to evaluate the associations between work productivity and disease activity/physical functioning. RESULTS: Absenteeism in 51 patients with axSpA was low (8.3 %). A decrease in work productivity was related to an increase in disease activity. Disease activity was strongly correlated with absenteeism (p < 0.01), presenteeism (p < 0.01) and work productivity loss (p < 0.001). In addition, decreased work productivity was related to a decrease in functional ability. Physical functioning was correlated with absenteeism (p < 0.001), presenteeism (p < 0.05) and work productivity loss (p < 0.001). CONCLUSIONS: Impairment of work productivity was correlated with disease activity and physical functioning in Italian patients with axSpA with CBP for ≥3 months and ≤2 years, with onset <45 years of age.

Detection of Calcium Crystals in Knee Osteoarthritis Synovial Fluid: A Comparison Between Polarized Light and Scanning Electron Microscopy.

BACKGROUND: The identification of calcium crystals in synovial fluid (SF) of patients with osteoarthritis (OA) represents an important step in understanding the role of these crystals in synovial inflammation and disease progression. OBJECTIVES: This study aimed to investigate the presence of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in SF collected from patients with symptomatic knee OA by scanning electron microscopy (SEM) coupled to x-ray energy dispersive spectroscopy, compensated polarized light microscopy (CPLM), and alizarin red staining. METHODS: Seventy-four patients with knee OA were included in the study. Synovial fluid samples were collected after arthrocentesis and examined under CPLM for the assessment of CPP crystals. Basic calcium phosphate crystals were evaluated by alizarin red staining. All the samples were examined by SEM. The concordance between the 2 techniques was evaluated by Cohen κ agreement coefficient. RESULTS: Calcium pyrophosphate and BCP crystals were found, respectively, in 23 (31.1%) and 13 (17.5%) of 74 OA SFs by SEM analysis. Calcium pyrophosphate crystals were identified in 23 (31.1%) of 74 samples by CPLM, whereas BCP crystals were suspected in 27 (36.4%) of 74 samples. According to κ coefficient, the concordance between CPLM and SEM was 0.83 for CPP, and that between alizarin red and SEM was 0.68 for BCP. CONCLUSIONS: The results of our study showed a high level of concordance between the 2 microscope techniques as regards CPP crystal identification and a lower agreement for BCP crystals. Although this finding highlights the difficulty in identifying BCP crystals by alizarin red staining, the use of SEM remains unsuitable to apply in the clinical setting. Because of the in vitro inflammatory effect of BCP crystals, further work on their analysis in SF could provide important information about the OA process.

A recently developed MRI scoring system for hand osteoarthritis: its application in a clinical setting.

This study aimed to apply the recently proposed Oslo hand osteoarthritis magnetic resonance imaging (MRI) scoring system to evaluate MRI findings in a cohort of patients affected by long-standing erosive hand osteoarthritis (EHOA). Eleven female EHOA patients (median 59 [interquartile range 62-52] years, disease duration 9.5 [interquartile range 13-3.75] years) underwent MRI (1.5 T) of the dominant hand, and synovitis, bone marrow lesions (BMLs), joint space narrowing, osteophytes, cysts, malalignment, and erosions were scored using the Oslo scoring system. Intra- and inter-reader reliability were assessed. The patients also underwent X-ray examination, and bone features were evaluated using the same scoring system. Pain and tenderness were assessed during a physical examination. Spearman's non-parametric test was used to analyze the correlations between variables. MRI intra- and inter-reader reliability were found between good and moderate for many features. No statistical differences were found between the radiographs and MRI with regard to detection of JSN, malalignment, and bone erosions. Synovitis was detected in 39.8 % of the 80 joints examined (in a mild form in 80 %), erosions were found in 51.1 %, and BMLs were identified in 20.5 and 23.9 % at the distal and the proximal side, respectively. BMLs at both the proximal and distal ends were correlated with tender joints (BML distal p = 0.0013, BML proximal p = 0.012). The presence of synovitis was correlated with tenderness (p = 0.004) and erosions at both the distal and proximal joints (p = 0.004). The presence of erosions correlated with tender joints (p < 0.01) and the mean visual analog scale (VAS) score (distal p = 0.03, proximal p = 0.01). Synovitis and BMLs were correlated with clinical symptoms in our patients affected with long-standing EHOA.

The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints.

The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

The controversial relationship between osteoarthritis and osteoporosis: an update on hand subtypes.

AIM: To compare hand osteoarthritis (HOA) subtypes and to examine possible links with local bone mineral density (BMD). METHOD: Fifty-five patients with erosive hand osteoarthritis (EHOA) and 21 patients with nodal hand osteoarthritis (NOA) fulfilling American College of Rheumatology criteria for HOA were evaluated. Subjects showing at least two erosions of the interphalangeal joints were assigned to the EHOA group; the others were considered NOA. Disease duration, number of active joints and radiological scores were assessed. All patients and 174 controls underwent phalangeal radiographic absorptiometry (pRA) of the middle phalanges of the non-dominant hand to assess BMD, T- and Z-scores. RESULTS: BMD was higher in EHOA with respect to NOA and controls (P = 0.05); T- and Z-scores were significantly higher in EHOA (P = 0.01 and P < 0.01). Values suggestive of osteopenia were found in 32% of EHOA and 22% of NOA patients, and in 44% of controls (P = 0.05 EHOA vs. NOA); a T-score < -2.5 standard deviations was present in 15% of EHOA and 28% of NOA patients, and in 21% of controls (P = 0.05 EHOA vs. NOA). CONCLUSION: Phalangeal BMD was higher in EHOA compared to NOA and controls. This characteristic could potentially be exploited to differentiate the two hand OA subtypes.

Ex Vivo Signaling Protein Mapping in T Lymphocytes in the Psoriatic Arthritis Joints.

We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6Rα (IL-6Rα) expression in the inflammatory microenvironment of synovial fluid (SF) of patients with sustained psoriatic arthritis (PsA). Our approach was to measure the IL-6 level in SF using a multiplex bead immunoassay. Reverse-phase protein array was used to assess Janus kinase (JAK) 1 and JAK2, extra-cellular regulated kinase (ERK) 1 and 2, protein kinase Cδ (PKCδ), signal transducer and activator and transcription (STAT) 1, STAT3, and STAT5 phosphoproteins in total T cell lysates from SF of patients with PsA. Frequencies of CD4+IL-17A-F+IL-23+ CD4+ Th cells producing IL-17A and IL-17F (Th17) and CD4+CD25high intracellular forkhead box transcription factor+ (FOXP3+) phenotypes, and the percentage of Treg- and Teff- cells were quantified in SF and matched peripheral blood (PB) of patients with PsA and PB of healthy controls (HC) by flow cytometry. Our results were the following: In PsA SF samples, a coordinate increase of JAK1, ERK1/2, STAT1, STAT3, and STAT5 phosphoproteins was found in total T cells in SF of PsA; where IL-6 levels were higher than in PB from HC. Expanded CD4+IL-17A-F+IL-23+ Th17, CD4+ CD25- Teff- and CD4+CD25(high) FoxP3+Treg subsets, showing similar levels of enhanced IL-6Rδ expression, were confined to PsA joints. In our studies, the transcriptional network profile identified by ex vivo signaling protein mapping in T lymphocytes in PsA joints revealed the complex interplay between IL-1, IL-6, and IL-23 signaling and differentiation of Th17 cells and CD4+Tregs in sustained joint inflammation in PsA.

Lengthening the time intervals between doses of biological agents in psoriatic arthritis patients: A single-center retrospective study.

Anti-tumor necrosis factor (TNF) alpha therapy has changed the course of psoriatic arthritis (PsA), but clinical experience about lengthening of time intervals between drug administrations is still limited. The aims of the study were to evaluate: (1) the long-term efficacy (over a 4-year period) of etanercept/adalimumab in a subset of PsA patients who did not require switches; and (2) the progressive lengthening of time intervals between treatments in patients who achieved minimal disease activity (MDA). PsA outpatients attending the Rheumatology Clinic-University of Padova who took a single anti-TNF agent (etanercept/adalimumab) for a 4-year period were studied. Therapy efficacy was assessed using clinical, biochemical, and disease activity (DA) indexes. The intervals between treatments were empirically and progressively lengthened after MDA was reached and maintained. One hundred and forty-one patients (mean age, 51.22 ± 12.34 years; mean disease duration, 12.1 ± 8.42 years) treated with etanercept/adalimumab (47.5% and 52.5%, respectively) were studied. DA indexes showed a marked, persistent improvement in all the patients throughout 4 years. The interval between injections could be extended in 46.1% of the patients (35% for adalimumab, 58% for etanercept) without provoking relapses. The mean therapy interval at the end of the study period was 3.12 weeks for adalimumab 40 mg (with respect to 2 weeks) and 2.75 weeks for etanercept 25 mg (with respect to 0.5 weeks). The new therapy timetable also led to cost savings. In conclusion, lengthening the time intervals between injections of anti-TNF agents in PsA patients who reach MDA is safe, effective, cost-effective, and facilitates patient compliance.

Transcriptional network profile on synovial fluid T cells in psoriatic arthritis.

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1ß, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1ß levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1ß and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.

Predictors of response and drug survival in ankylosing spondylitis patients treated with infliximab.

BACKGROUND: The advent of anti-tumor necrosis factor-α (TNFα) drugs has changed the course of ankylosing spondylitis (AS). While data are available concerning the long term effectiveness of single anti-TNF agents, little has been published about predictors of treatment response in AS. The aim of this retrospective study was to evaluate the survival, effectiveness, and safety of infliximab over a 5-year period and to identify predictors of disease outcome. METHODS: Seventy AS patients attending the Rheumatology Clinic of the University of Padua who were treated with intravenous infliximab at 0, 2, 4 weeks and then every 6, 8, or up to 16 weeks were studied retrospectively. Demographic information, laboratory inflammatory and disease indices (BASDAI, BASFI, BASMI) were collected (at baseline, 3, 6, 12 months and once a year thereafter). Clinical improvement, drug tolerability, adverse events/side effects and causes leading to discontinuation were recorded. RESULTS: Infliximab caused a rapid, persistent improvement at all the assessment times in the BASDAI 50 (71.4 %) and ASDAS scores (97.1 % in ASAS20, 80 % in ASAS40, 80 % in ASAS5/6), and already within 6 months of beginning treatment in 50 % percent of the patients. The other 50 % withdrew because of: adverse events (12 = 34.3 %), side effects (5 = 14.3 %), drug inefficacy (12 = 34.3 %), spontaneously (4 = 11.4 %). Those who did not respond were prevalently females (34.3 % vs 17.1 %). CONCLUSION: Factors such as female sex, use of steroids, persistently high inflammatory levels, BASFI and BASDAI indices were found to be negative predictors of treatment response. Infliximab was found to be safe, effective and well-tolerated; it elicited satisfactory long term response and drug survival rates.

IL-1ß and IL-8 are scavenged by the hexadecylamide derivative of hyaluronic acid: a new mechanism.

This study aimed to investigate, using an in vitro model, the mechanisms involved in the effects linked to a novel hexadecylamide derivative of hyaluronic acid (HA), HYADD®4 (HS), on some inflammatory aspects related to the osteoarthritis process. The human leukemic monocytic cell line THP-1 was stimulated with calcium pyrophosphate (CPP) crystals or lipopolysaccaride (LPS) and cultured in the presence of HS or two unmodified HAs (500-730 kDa and >1500 kDa, respectively). The effects of the three HA derivatives were compared by examining the inhibition of IL-1ß and IL-8 release, the phagocytic capacity of THP-1, and HA's physical interference with the cytokines and their biological activity. Adding HS simultaneously with the stimuli led to a marked (nearly 100%) decrease in cytokine release and biological activity with respect to the two unmodified HAs. The effect was not altered when a CD44 function-blocking monoclonal antibody was used. Incubation of the three derivatives with IL-1ß and IL-8 led to a reduced bioavailability of the cytokines in the medium in the presence of HS but not of unmodified HA. This study examines a novel mechanism inhibiting cytokine bioactivity. The HA hexadecylamide derivative was found to suppress, in vitro, the inflammatory response induced by CPP crystals and LPS by reducing the bioavailability of the two cytokines that were analyzed.

Atherosclerosis progression in psoriatic arthritis patients despite the treatment with tumor necrosis factor-alpha blockers: a two-year prospective observational study.

OBJECTIVE: To evaluate the progression of subclinical atherosclerosis in Psoriatic Arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α agents. METHODS: Thirty-two PsA patients classified according to the CASPAR criteria and attending the Rheumatology Unit of the University of Padua Medical Center were enrolled in a two-year prospective, observational study. In accordance with the ASAS/EULAR recommendations on the management of these patients, those studied were prescribed biological agents [etanercept (n=21), adalimumab (n=6), infliximab (n=5)]. Plasma lipids, inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), vessel endothelium growth factor (VEGF), osteoprotegerin (OPG), and TNF-α, as well as Disease Activity Score 28 calculated with CRP (DAS 28-CRP) were evaluated at baseline and after two years of treatment. Bilateral carotid B-mode ultrasound measurements [the mean-intima media thickness (mean-IMT), the mean maximum-IMT (M-Max)] of each carotid artery segment (common, bulb, and internal carotid artery) and the post-occlusion flow-mediated dilation (FMD) of the brachial artery were also assessed at baseline and after two years. RESULTS: Despite an improvement in the DAS 28-CRP score (P<0.0005) and lower low-density lipoprotein cholesterol (P<0.013) and triglyceride (P<0.036) values, there was a significant progression in both the mean-IMT (P<0.0005) and M-Max (P<0.0005). Moreover, no recovery in FMD (P=ns) was observed after two years of anti TNF-α treatment. Serum TNF-α levels were increased (P=0.003) and OPG values were decreased (P=0.011) at the end of follow- up with respect to baseline values. CONCLUSIONS: Despite improvement in clinical status, arterial remodelling was observed in the PsA patients who were treated with anti TNF-α agents for two years.