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The debilitating effects of non-communicable diseases (NCDs) and the accompanying chronic inflammation, represent a significant obstacle for the sustainability of our development, with efforts being spread worldwide to contrast NCDs’ diffusion, as per the United Nations Sustainable Development Goals (SDG 3). In fact, despite efforts of variable intensities in numerous directions (from innovations in biotechnology to lifestyle modifications), NCDs’ incidence remains pandemic.The present work wants to contribute to this major concern with a specific focus on the fragmentation of the medical approaches, via an interdisciplinary analysis of themedical discourse, i.e. the heterogenous reporting that biomedical scientific literature uses to describe the anti-inflammatory therapeutic landscape in NCDs. The aim is to better capture the roots of this compartmentalization and the power relations existing among three segregatedpharmacological, experimentalandunstandardizedbiomedical approaches, to ultimately empower collaboration beyond medical specialties and possibly untap a more ample and effective reservoir of integrated therapeutic opportunities.Using as exemplar disease rheumatoid arthritis (RA), twenty-eight articles were manually translated each into a nine-dimensional categorical variable of medical socio-anthropological relevance, relating in particular (but not only) tolegitimacy, temporalityandspatialization. This digitalized picture (9 × 28 table) of the medical discourse was further analyzed by simple automatic learning approaches to identify differences and highlight commonalities among the biomedical categories.Interpretation of these results gives original insights including the suggestion to: empower scientific communication betweenunstandardizedapproaches and basic biology; promote non-pharmacological therapies repurposing to enhance robustness ofexperimentalapproaches; align the spatial representation of diseases and therapies inpharmacologyto effectively embrace thesystemicapproach promoted by modern personalized and preventive medicines. We hope this original work may expand and foster interdisciplinarity among public health stakeholders, ultimately contributing to the achievement of SGD3.

Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis.One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones.Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade 2, soft tissue edema and subcutaneous PDUS signal (p 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p 0.001).Digital tenderness and pain are linked to US tenosynovitis of grade 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.

Objective.To use ultrasonography to study whether the duration of psoriatic dactylitis was associated with different patterns of extracapsular and synovial-based involvement.Methods.One hundred cases of hand dactylitis from 85 patients with psoriatic arthritis (PsA) were consecutively enrolled in a multicenter cross-sectional study and divided into 2 groups according to dactylitis duration (shorter or longer than the median: 20 weeks). All dactylitis fingers were investigated using high-frequency ultrasound both in greyscale (GS) and power Doppler (PD), evaluating the presence of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDS), extensor tendon involvement, and joint synovitis.Results.Cases with a shorter dactylitis duration (< 20 weeks) had a significantly higher prevalence of GS flexor tenosynovitis of grade > 2, PD flexor tenosynovitis, soft tissue edema, and subcutaneous PDS (p = 0.001, p < 0.001, p < 0.05, and p = 0.001, respectively). However, the presence of synovitis in GS and PD mode (in both cases at proximal interphalangeal level) was more frequent in patients with longer dactylitis duration (p < 0.001). When detected in the chronic form, flexor tenosynovitis was grade 2 or lower.Conclusion.In a large cohort of PsA hand dactylitis, we found a predominant extracapsular inflammation (flexor tenosynovitis and soft tissue edema) in early cases and a high prevalence of joint synovitis at proximal interphalangeal level in the chronic form. However, longitudinal imaging studies are needed to clarify these aspects.

Introduction The aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting. Methods An observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria. The Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were used as objective and self-reported functional indices. The improvement of function and factors associated were evaluated for the present study, as well as disease activity and patient-reported outcome measures. Results A total of 183 patients with axial SpA were examined. Among them, 27 were non-radiographic axial SpA, while the remaining 156 were ankylosing spondylitis patients. BASFI and BASMI significantly improved during follow-up. Improvement of metrology index BASMI inverse correlated with disease duration (rho − 0.2, p = 0.009) and directly correlated with the improvement of BASDAI (rho 0.26, p = 0.003) and CRP (rho 0.26, p = 0.0003). Improvement of BASFI significantly inversely correlated with disease duration and directly correlated with the improvement of BASDAI, CRP, and baseline ESR. Male sex, lower disease duration, high ESR, and the improvement of BASDAI were found to be associated with the improvement of BASFI. Conclusions Our results showed that in real-life settings, patients improve in BASMI and BASFI. Furthermore, factors associated with this improvement were identified.

No abstract available

To evaluate, by means of a longitudinal study, radiographic involvement of metacarpophalangeal and radio-carpal joints in hand osteoarthritis, its relationship with erosive disease and its progression, 368 patients with hand osteoarthritis were enrolled. All patients underwent hand X-rays. On the basis of the presence of central erosions in interphalangeal joints, patients were divided into three groups: 0-no central erosions, 1-one joint with central erosion, and 2-two or more joints with central erosions. A longitudinal study on 44 patients and nine normal controls, whose X-rays were available after 3.9 years, was performed. The radiological involvement of metacarpophalangeal and radio-carpal joints was evaluated using Kellgren-Lawrence and OARSI scores. Low number of joints showed Kellgren-Lawrence values ≥2 group 0, 42/1290 (3.3%); group 1, 10/410 (2.4%); and group 2, 36/1980 (1.8%). Low score values were obtained for all radiographic items. Only metacarpophalangeal joint space narrowing score showed significant increase from groups 0 to 2. Subsequent adjustment for age, gender, and BMI did not confirm the statistical significance. Marginal erosions were rarely found (6.7% of joints). Metacarpophalangeal and radio-carpal radiographic per patient scores significantly worsened at follow-up, but no significant increase in joints with Kellgren-Lawrence score ≥2 was found. In normal controls, no significant radiographic worsening was found. Only a minority of metacarpophalangeal joints shows a Kellgren-Lawrence value ≥2. Metacarpophalangeal and to lesser extent radiocarpal joints had significant worsening at follow-up. Metacarpophalangeal joint involvement in hand osteoarthritis is mild but progressive. Radiocarpal involvement is negligible.

Background Several studies have identified a central role for the activation of the complement system in the pathogenesis of OA, finding an abnormally high expression and activation of complement in human osteoarthritic joints and the specific contribution of complement (C) components 5 and 6 and the membrane attack complex (MAC) (1). The complement system consists of several proteins which contribute to an enzymatic cascade ending in lysis. Two main, different pathways converge into C3 factor activation. In the classical pathway C4 is involved, while in alternative pathways Factor-b (FB) is involved. Objectives The aim of this study was to investigate the expression of complement factors (C3, C4 and FB) and activation fragments (C3a, C5a, FBa, MAC) in OA joint tissues. Methods Osteochondral biopsies from 33 patients (16 OA, 12 Rheumatoid Arthritis-RA and 15 Postraumatic cases-PT) who underwent knee, hip or shoulder arthroplasty were collected. Immunohistochemistry and quantitative Imaging analysis were perfomed to analyze C3, C4 and CFB expression. Cartilage pathology was evaluated utilizing Mankin score. Chondrocytes, synoviocytes, cartilage and synovial biopsies were obtained from 11 OA patients undergoing joint replacement surgery. Cultures were set up with or without pro-inflammatory (IL-1beta) stimulus. Culture supernatants were analyzed for C3a, C5a, CFBa and C5b-9 production using enzyme-linked immuno-sorbent assay (ELISA). Statistical analysis was performed utilizing Wilcoxon matched pairs test and Mann Whitney’s test, using Graph Pad Prism software. Results In osteochondral biopsies, C factor expression was located in bone marrow and in a few subchondral bone cells. C3 was the most expressed factor in all patient subtypes while factor C4 had a very low expression, except for some sporadic cases. (OA: C3 vs FactorB p=0.0280, C3 vs C4 p=0.0005; RA: C3 vs FactorB p= 0.0269, C3 vs C4 p=0.0005; PT: C3 vs FactorB p=ns, C3 vs C4 p=0.0001) CFB was significantly augmented in PT and was not significantly different between OA and RA. C factors expression did not correlate with Mankin score or with the joint type (knee, hip or shoulder). Cell positivity was mainly present in the subchondral bone (bone marrow) whereas cartilage was almost negative. As to activation fragments, C3a was the most produced factor (vs C5a and CFBa p Conclusion Complement factors were expressed mainly in bone marrow and in a few subchondral bone cells, but not in cartilage. Complement activating fragments are produced by chondrocytes and synoviocytes. The dissimilar expression of activating fragments by different cell types could suggest various C activating mechanisms in joint tissues. Reference [1] Wang Q, et al. Nat Med 2011;17:1674-1679. Disclosure of Interests None declared

Objectives: To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis. Methods: Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment. Results: The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons). Conclusions: Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.

No abstract available

Background: The aim of this global collaboration was to develop a consensual set of items for the analysis of synovial biopsies in clinical practice and translational research through the EULAR Synovitis Study Group (ESSG) and OMERACT Synovial Tissue Biopsy Group. Methods: Participants were consulted through a modified Delphi method. Three sequential rounds occurred over 12 months. Members were sent a written questionnaire containing items divided into two parts. Items were identified and formulated based on a scoping review. The first part of the questionnaire referred to synovial biopsies in clinical practice including five subsections, and the second part to translational research with six subsections. Every participant was asked to score each item on a 5-point Likert scale. Items with a median score above 3.5 and a ≥ 70% agreement were selected for the next round. The last round was conducted orally at EULAR in June 2017. Results: Twenty-seven participants from 19 centers were contacted by email. Twenty participants from 17 centers answered. Response rates for next rounds were 100%. For the first part relating to clinical practice, 20/44 items (45.5%) were selected. For the second part relating to translational research, 18/43 items (41.9%) were selected for the final set. Conclusions: We herein propose a consensual set of analysis items to be used for synovial biopsies conducted in clinical practice and translational research.

Background & Aim Adipose mesenchymal stromal cells (ASC) are commonly utilized in various cell therapies and recently in phase I clinical trials to counteract the development of knee osteoarthritis. Administered-ASC in the knee joints enter in close contact with the OA inflammatory milieu and hypoxic environment,which could modulate their characteristics.Little is known about the OA milieu factors that could enhance the migration and tissue specific engraftment of exogenously injected ASC for successful regenerative cell therapy.Therefore,we tested the effect of OA milieu on good manufactured practice (GMP)-ASC,both in normoxic and hypoxic conditions and evaluated their migration properties and cytokine receptors. Methods, Results & Conclusion We analyzed IL8, IP10,SDF-1,MCP1,MIP1α, MIP1β,RANTES and IL6 cytokines in two different OA milieu:OA synovial fluid (SF) and OA-conditioned medium (CM) from synoviocytes.These milieu adequately represent the OA environment for ASC injection and the milieu containing all the soluble factors released by the target tissue of ASC, respectively. The same cytokines were analyzed also on basal GMP-ASC,both in normoxic and hypoxic conditions. Afterwards, GMP-ASC were treated either with OA-SF or OA-CM for 48hours and tested for migration and cytokine receptors expression, as well as the cytokine secretion, both in normoxia or hypoxia (1,5%O2). Healthy SF was used as control. In OA-SF we detected higher amount of IP10 than in OA-CM while MCP1 and MIP1β were higher in OA-CM compared to OA-SF.All the other cytokines were detected in the same amounts in both OA milieu. We demonstrated that GMP-ASC show an increase in proliferation, migration, no changes in the amount of cytokines released and modulation of CXCR1,CXCR3,CCR1 and CCR5 receptors in hypoxic condition. Moreover,GMP-ASC migration increased 15-fold when treated either with OA-SF or OA-CM compared to healthy SF,both in normoxic and hypoxic conditions.GMP-ASC treated in OA milieu showed an increase of CXCR3, CCR3 and IL6R and a decrease of CCR1,CCR2 receptors. IP10 was the only chemokine of the OA milieu down-modulated after treatment with GMP-ASC.We demonstrated specific effects of OA milieu on both GMP-ASC migration and cytokine receptor expression that were strictly dependent by the inflammatory and hypoxic environment.The use of characterized OA milieu might contributes to define the therapeutic effects of GMP-ASC and indicates that IP10-CXCR3 axis is partially involved in GMP-ASC effect on synovial macrophages.

Objective To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behcet's disease (BD). Methods A multicenter study evaluating 18 refractory BD patients with major vessel involvement [pulmonary artery (n = 4), aorta (n = 4) or peripheral artery aneurysm (n = 1) and/or pulmonary artery (n = 7), inferior vena cava (n = 5), or intra-cardiac (n = 3) thrombosis or Budd Chiari Syndrome (n = 2)] treated with anti-TNFα agents. Results Vascular remission was achieved in 16 (89%) patients. The 9 months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy [OR = 8.7 (1.42–62.6), p = 0.03]. The median daily dose of corticosteroids significantly decreased at 12 months. Side effects included infection (n = 4) and pulmonary edema (n = 1). Conclusion TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9 months compared to conventional immunosuppressants in BD patients with major vessels disease.

Background Inflammatory rheumatic joint diseases such as Ankylosing Spondylitis (AS) and Rheumatoid Arthritis (RA) have recently been found to be associated with sleep disturbances especially obstructive sleep apnoea.1 2 Objectives The aim of our study was to evaluate the occurrence of sleep disturbances, especially REM Sleep Behaviour Disorder (RBD), in inflammatory rheumatic diseases, (rheumatoid arthritis -RA and Spondyloarthritides -SpA). Methods We enrolled 103 consecutive patients affected by inflammatory rheumatic diseases [RA (64, 62.1%) or SpA (39, 37.9%)]. Patients underwent a neurologic and psychopathological assessment, including identification of sleep disorders by means of the Pittsburgh Sleep Quality Index (PSQI), the Berlin and the REM sleep behaviour disorder (RBD) questionnaires, a structured interview on sleep terrors and sleep paralysis, Beck Depression Inventory (BDI-II) and the Spielberger State-Trait Anxiety Inventory (STAI). Statistical analysis was performed utilising SPSS software. Results No significant differences were found between RA and SpA patients in age at diagnosis, disease duration, smoke habit, alcohol consumption, anamnestic comorbidities (especially metabolic diseases, anxiety or depression), disease activity/remission and biologic Disease Modifying Antirheumatic Drugs use. No differences demonstrated in BDI-II, STAI, PSQI and RBD questionnaires; only the Berlin Questionnaire showed significant differences (17.2% in RA vs 35.9% in SpA, p=0.036). No differences in sleep paralysis (10.9% in RA vs 7.7% in SpA, p=0.74) and sleep terrors (37.5% in RA vs 20.5% in SpA, p=0.0826) which were found to be increased if compared with general population (2.6%.) Conclusions Our data show an increased prevalence of sleep terrors in rheumatic patients when compared to the general population although no differences were highlighted between RA and SpA; also increased risk of sleep apnoea (Berlin Questionnaire) has been demonstrated in patients with SpA compared with RA. References [1] Aydin E, Bayraktar K, Turan Y, Omurlu I, Tastaban E, Sendur OF. Sleep quality in patients with ankylosing spondylitis. Rev Bras Reumatol2015;55:340–5. [2] Taylor-Gjevre RM, Nair BV, Gjevre JA. Obstructive sleep apnoea in relation to rheumatic disease. Rheumatology2013;52:15–21. [3] American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed, American Academy of Sleep Medicine, Darien, IL 2014. Disclosure of Interest None declared

Purpose: To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). Methods: 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren–Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. Results: Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. Conclusions: This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.

Objective.The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA).Methods.In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease.Results.Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients.Conclusion.Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.

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Objective: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). Methods: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. Results: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2±0.5 vs 1.7±2.4 before the use of anti-TNF, p

Objectives To describe the response to IL-6 blockade [tocilizumab (TCZ)] in three patients affected by highly refractory neuro-Behcet disease (NBD). Methods Three patients who had failed synthetic immunosuppressants and TNF-α antagonists combined with glucocorticoids received TCZ after obtaining their informed consent. Two patients underwent TCZ infusions at 8mg/kg every 4 weeks for a mean period of 24 months, while in one patient, the frequency of TCZ infusions was increased to every other week after 21 months due to a disease flare. Concomitant therapy with synthetic agents and low-to-medium dose glucocorticoids was continued. Clinical and imaging findings were assessed before and after the onset of TCZ therapy. Results In all our patients, a very short time lag between the onset of treatment with TCZ and the clinical response was observed. A partial response occurred in two patients and a nearly complete response in one. Some loss of efficacy occurred after 18 months in one patient, but there was again a significant improvement when the interval between the infusions was shortened. TCZ was overall well tolerated and no serious adverse events occurred. In two patients, the prednisone dose could successfully be tapered to about 20mg/day, while in another patient glucocorticoids could safely be withdrawn. Brain MRI remained virtually unchanged in all patients. Conclusions Although TCZ has not yet been included among the medications recommended for the treatment of NBD, our data suggest that it may be considered for patients with refractory NBD.

Objective.To investigate the possibility of achieving partial remission (PR) in patients with nonradiographic axial spondyloarthritis (nr-axSpA) versus ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (TNF)-α antagonists, such as adalimumab (ADA), etanercept (ETN), and infliximab (IFX), in a real clinical practice setting. The Assessment of SpondyloArthritis international Society (ASAS) 20, ASAS40, and Ankylosing Spondylitis Disease Activity Score were also calculated.Methods.A retrospective study was conducted in patients with axSpA treated with ADA, ETN, and IFX from 2000 to 2013. All patients fulfilled the ASAS or the modified New York criteria. PR was reached when the score was < 20 mm (on a visual analog scale of 0–100 mm) in each of these domains: (1) patient global assessment, (2) pain, (3) function, and (4) inflammation.Results.A total of 321 patients with axSpA were treated. Among them, 62 were nr-axSpA while the remaining 259 were AS. Log-rank test to compare survival curves showed that the probability of obtaining PR in nr-axSpA and AS during treatment with anti-TNF-α was not significantly different. At 12 weeks of exposure to the first anti-TNF-α drug, PR was achieved in 7 patients with nr-axSpA (11.3%) and in 68 patients with AS (26.2%).Conclusion.Our results, obtained from clinical practice, showed that PR is an achievable target of anti-TNF-α treatment in nr-axSpA. The PR rate, as a reliable indicator of sustained effectiveness, is similar in nr-axSpA and in AS.

Introduction Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). Objectives To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA. Methods We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. Results We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE. Conclusions RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

ObjectiveBoth excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms.MethodsOsteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus.ResultsWNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos.ConclusionsIn osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells.

Background: Ultrasound is one of the most promising candidates for the detection of inflammation and structural damage in hand osteoarthritis. Objective: To evaluate new advances of US as a diagnostic and prognostic tool in hand osteoarthritis assessment. Methods: We conducted a Medline on PubMed search for articles about “ultrasonography” and “hand OA” published between January 2012 and 15th April 2016, limiting our search to articles on human adults in English, excluding those involving systemic inflammatory diseases, visualization of joints other than hands, ultrasound guided injections and surgical procedures. Reviews, case reports, letters, position statements and ex vivo studies were excluded. Concordance between ultrasound and conventional radiography and magnetic resonance imaging was evaluated. Results: Total 46 records were identified, and 16 articles were selected: four showed only ultrasound structural damage (osteophytes, cartilage pathology), six only ultrasound inflammatory variables (synovial thickness, effusion and power Doppler signal), six should considered both ultrasound structural and inflammatory features as well as erosions and two were epidemiological studies. Ultrasound synovitis and power Doppler signal were more frequent in erosive hand osteoarthritis. Followup studies found that ultrasound inflammatory features at baseline are independently associated with radiographic progression; power Doppler signal was the strongest predictor of structural damage. Ultrasound is a reliable tool for cartilage and osteophyte assessment (when performed with static images) and shows a good concordance with magnetic resonance imaging for osteophytes, erosions and synovitis. Conclusions: Ultrasound detected inflammation may predict radiographic progression and may be used in prospective clinical trials of hand osteoarthritis and in everyday clinical practice.

The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.

Objectives To investigate the prevalence of REM sleep behavior disorder (RBD) in patients with inflammatory arthritis (IA) to ascertain if RBD could be an internal red flag signaling a fluctuating state of inflammation based on the theory of “protoconsciousness”. Materials & Methods One hundred and three patients with a confirmed diagnosis of IA were consecutively recruited. The patients underwent general (IA activity, functional status, laboratory tests) and neurological evaluations. A neurologist investigated RBD and REM sleep parasomnias in a semi‐structured interview. Sleep quality was assessed with the Pittsburgh Sleep Quality Index, while the risk of obstructive sleep apnea syndrome (OSAS) was evaluated with the Berlin questionnaire. Beck Depression Inventory II and State‐Trait Anxiety Inventory investigated depression and anxiety. Results Patients had a mean age of 53.7 ± 14.6 years, 65% were women; 57.3% were in a clinically active phase of IA. Two women fulfilled ICSD‐3 criteria for RBD appearing 11 years after and 20 years before IA onset respectively. 31 patients scored positive for nightmare disorder (ND), 8 for recurrent isolated sleep paralysis. 65 (63.1%) patients reported poor sleep quality and 25 (24.3%) resulted at high risk for OSAS. 32 (31.0%) patients scored positively for depression or anxiety. Conclusions The prevalence of RBD in patients with IA did not differ from that in the general population, whereas ND presented a 2‐fold increased prevalence. Whether RBD can be considered a red flag signaling an internal danger remains an open question, while ND may be a new player in this intriguing relation.

Objective.The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment.Methods.In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion.Results.One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2–6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625–2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP ≥ 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4–11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23–6.82, p = 0.015) were the only factors predictive of disease reactivation.Conclusion.In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation.

To report the safety and efficacy of anti-tumor necrosis factor a (TNFα) therapy in severe and refractory neuro-Behcet disease (NBD) patients. Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24-60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n=13] or adalimumab [n=4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months. Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1-6). The median Rankin score was 2 (1-4) at the initiation of anti-TNFα versus 1 (0-4) at the time of remission (P=0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases. TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and involvement of nail and enthesis), and it usually requires a multidisciplinary treatment approach. Tumor necrosis factor-α (TNF-α) is overexpressed in psoriatic synovium and skin plaques and its selective inhibition by anti-TNF-α agents has been demonstrated to reduce TNF-α levels in the articular environment, reversing the synovial hyperproliferative phenotype. Studies performed on anti-TNF-α agents in PsA demonstrated that they are able to reduce neutrophil and macrophage infiltration as well as vascular cell adhesion protein 1 expression with ensuing synovial thickness normalization. The efficacy of anti-TNF-α agents for all PsA manifestations (peripheral arthritis, axial involvement, enthesopathy, and skin disease) suggests that anti-TNF-α efficacy might be related to the ability to influence angiogenesis and osteoclastogenesis, reduce synovial inflammation, and slow radiological disease progression. This review describes the role of anti-TNF-α in each manifestation of PsA.

Summary Objective To evaluate the association between ultrasound (US) detected inflammation at baseline and the subsequent development of new bone erosions at follow-up in patients with hand osteoarthritis (HOA). Method 32 of the 35 (10 controls, 12 patients with non erosive HOA (non-EHOA), 13 with EHOA subjects originally studied were re-evaluated 3.9 years after the initial study, by means of standard radiography and US examination. Kellgren–Lawrence (K-L) and Kallman scores were utilized to evaluate 576 interphalangeal (IP) joints. US detected synovial inflammation features were scored as present/absent. US detected bone erosions were also investigated. The association between synovial inflammation features at baseline and the development of new bone erosions was evaluated using the generalized linear mixed model (GLMM) after adjustment for patient effect, age, gender, body mass index. Results In HOA patients, radiographic scores worsened and bone erosions progressed. In HOA patients similar percentages of joints with Power Doppler Signal (PDS) and gray scale (GS) synovitis were found comparing baseline and follow-up examinations, whilst a significant increase was found in the joints with effusions. Only a minority of joints were positive on both occasions (between 2 and 6 %), the majority fluctuated between positive and negative and vice versa. PDS positivity was associated with new radiographic central erosions and US-detected bone erosions, whereas GS synovitis and effusion were not. Conclusions Radiographic scores and bone erosions increased over a period of about 4 years. Synovial inflammation as detected by PDS was associated with the appearance of new bone erosions.

The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was

Behcet disease (BD) is a systemic inflammatory disease typically characterized by oral and genital ulcers and variable manifestations affecting other organs, mainly skin and eye. Published epidemiologic studies on BD are difficult to compare because of different study designs, settings, methods and the lack of universally accepted classification criteria: 16 different sets of classification/diagnosis criteria have been published so far; in the beginning of the chapter we compare different criteria subsets with estimates of sensitivity and specificity. After that, we review epidemiologic clinical studies (registries, hospital records, district databases): consistent data point to higher incidence and prevalence rates of BD along the ancient Silk Road (stretching from the Middle Est to the Far East and Mediterranean Countries) compared to a lower prevalence in Northern European Countries and United States genetic and environmental factors have been evaluated as well as age of onset, male-to-female ratio and systems involvement.

Objective: The primary objective of this retrospective study was to investigate the possibility of achieving partial remission (PR) in AS patients treated with anti-TNF-α antagonists, such as adalimumab (ADA), etanercept (ETA) and infliximab (INF), in a real clinical practice setting. Predictors of PR were also evaluated. Methods: A retrospective study was conducted in patients with AS treated with ADA, ETA and INF from 2000 to 2012. Kaplan-Meier survival curves were plotted to determine the rates of PR during the treatment with anti-TNF-α drugs. Results: A total of 283 patients with AS were treated with ADA (18.7%), ETA (26.8%) and INF (54.4%) as first anti-TNF-α drugs, with a PR rate of 57.6%. The probability of obtaining PR with ADA, ETA or INF was not significantly different among all anti-TNF-α patients. AS patients treated with a second anti-TNF-α drug had a PR rate of 40.5%, but after switching for lack of response, the probability of obtaining PR with a second anti-TNF-α drug was significantly lower from that of the first anti-TNF-α drug (P = 0.0039). The probability of obtaining PR in patients with enthesitis (P = 0.04) or psoriasis (P = 0.0016) or low levels of CRP (P = 0.0225) was significantly lower compared with that of patients without these manifestations at baseline. Conclusion: Our real-life study on PR confirmed the effectiveness of ADA, ETA or INF as first or second anti-TNF-α drugs. The presence at baseline of enthesitis or psoriasis or low CRP values yielded a lower probability of obtaining PR. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Objective. To assess the findings of temporal artery colour duplex sonography (CDS) in GCA characterized by a histological pattern of periadventitial small vessel vasculitis (SVV) and/or vasa vasorum vasculitis (VVV) and compare it with those observed in classic GCA with transmural vasculitis.Methods. We studied 30 patients with SVV and/or VVV, 63 patients with classic GCA and 67 biopsy-negative patients identified over a 9-year period. CDS of the temporal arteries was performed in all patients by one ultrasonographer. Temporal artery biopsy was used as the reference standard. Sensitivities, specificities and likelihood ratios (LRs) were calculated.Results. The frequency of the halo sign on CDS was significantly lower in the patients with SVV and/or VVV compared with those with classic GCA (20% vs 82.5%, P = 0.0001). The halo sign had a sensitivity of only 20% (95% CI 8.4, 39.1%) and a specificity of 80.6% (95% CI 68.7, 88.9%) for the diagnosis of SVV and/or VVV. The negative LR was 0.992 (CI 0.824, 1.195), and the positive LR was 1.030 (CI 0.433, 2.451). The halo sign for the diagnosis of biopsy-proven classic GCA had a higher sensitivity of 82.5% (CI 70.5, 90.5%), the same specificity of 80.6% (CI 68.7, 88.9%) and a higher positive LR (4.253; CI 2.577, 7.021).Conclusion. The halo sign is infrequently found in GCA characterized by a histological pattern of SVV and/or VVV. This limits the sensitivity of CDS in correctly identifying patients with GCA. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Un numero sempre crescente di evidenze sottolinea l’importante contributo dell’angiogenesi nell’ambito dei meccanismi che inducono le modificazioni articolari caratteristiche dell’osteoartrosi (OA). Nei pazienti con OA, alcune molecole correlate al processo angiogenetico, quali vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1) e fibroblast growth factor-2 (FGF-2) sono espresse a livello articolare e possono avere un ruolo non solo in relazione all’angiogenesi, ma anche all’omeostasi cartilaginea. Questo studio si propone di valutare i livelli circolanti di VEGF, VCAM-1 e FGF-2 in pazienti con OA della mano affetti da forma erosiva (OA-E) e non-erosiva (OA-NE) e di determinare le eventuali associazioni con il danno articolare valutato tramite analisi radiologica convenzionale. Sono stati analizzati, con metodo ELISA, i sieri di 146 pazienti con OA-E, di 148 pazienti con OA-NE e di 148 soggetti di controllo (CN). I livelli circolanti di sVCAM-1 nei pazienti con OA-E sono risultati più elevati rispetto a quelli evidenziati nei CN; non sono state dimostrate differenze tra i pazienti con OAE e i pazienti con OA-NE. L’analisi di VEGF e FGF-2 non ha evidenziato differenze significative tra pazienti con OA e CN, inoltre non sono emerse correlazioni tra i livelli circolanti di VEGF, sVCAM-1 e FGF-2 e parametri radiologici e clinici. I dati ottenuti, dimostrando un aumento dei livelli circolanti di sVCAM-1 nei pazienti con forma erosiva di OA della mano, caratterizzata da una peggiore decorso e maggiore aggressività, aggiungono nuove informazioni circa la possibilità di identificare sVCAM-1 come biomarcatore di severità di malattia.

This review focuses on the new perspectives which can provide insight into the crucial pathways that drive cartilage-bone physiopathology. In particular, we discuss the critical signaling and effector molecules that can activate cellular and molecular processes in both cartilage and bone cells and which may be relevant in cross talk among joint compartments: growth factors (bone morphogenetic proteins and transforming growth factor), hypoxia-related factors, cell–matrix interactions [discoidin domain receptor 2 (DDR2) and syndecan 4], signaling molecules [WNT, Hedgehog (Hh)]. With the continuous progression of our knowledge on the molecular pathways involved in cartilage and bone changes in osteoarthritis (OA), an increasing number of potentially effective candidates for OA therapy are already under scrutiny in clinical trials to ascertain their possible safe use in an attempt to identify molecules active in slowing or halting OA progression and reducing joint pain. We then review the principal molecules currently under clinical investigation.

Background Large vessel vasculitides (LVV) – Takayasu Arteritis (TA) and Giant Cell Arteritis (GCA) are inflammatory diseases of the aorta and its main branches. A cytokine cluster involving the IL-6 – IL-17 axis as well as another one centring on the IL-12-IFN-γ axis are involved in LVV pathogenesis. (1) Disease activity could be evaluated by measuring ESR and CRP as well as by using imaging techniques (Doppler Ultrasound, Computed Tomography scan, Magnetic Resonance Imaging or Positron Emission Tomography scan – CT/PET) and specific scoring systems (Indian Takayasu9s Arteritis Activity Score - ITAS and Kerr/National Institutes of Health index - Kerr / NIH) . To date, angiogenic factors have been evaluated but specific biomarkers for disease activity are still lacking (2) Objectives The aim of our study was to evaluate angiogenic and anti-angiogenic factor expression in LVV, in order to evaluate their role as biomarkers. Methods We enrolled 67 patients with LVV [TA (40, 59.7%) or GCA (27, 40.3%)] and 50 Normal Controls (NC). Angiogenic (angiopoietin-1, angiopoietin-2, Fibroblast Growth Factor2 – FGF-2, Vascular Cell Adesion Molecule1 – VCAM-1, Vascular Endothelial Growth Factor – VEGF) and anti-angiogenic (angiostatin, Endostatin-1, Pentraxin 3 – PTX3) factors were analysed using enzyme-linked immuno-sorbent assay (ELISA). Disease activity was evaluated according to Kerr (≥2) and ITAS (≥1) scores, only 47 (70.1%) patients underwent CT/PET. Serum levels of angiogenic and anti-angiogenic factors were compared among active LVV, inactive LVV and NCs. When evaluating disease activity according to CT/PET, it was considered active if SUV >2. Statistical analysis was performed utilizing Mann Whitney, Kruskal Wallis for multiple comparison and Dunn9s post hoc test, using Graph Pad Prism software. Results No significant differences were found between LVV and NCs in angiogenic factors. Conversely, anti-angiogenic factors were all significantly increased in LVV (both GCA and TA) in comparison with NCs (angiostatin: TA vs NC, p Conclusions Our data show an imbalance between angiogenic and anti-angiogenic factor levels in serum. No disease activity related changes were observed for these factors. References Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol 2013;9:731–740; Villa I, Bilbao MA, Martinez-Taboada VM. Advances in the diagnosis of large vessel vasculitis: identification of biomarkers and imaging studies. Rheumatol Clin 2011;7:S22-S27 Disclosure of Interest None declared

OBJECTIVES: To investigate the clinical associations of hand osteoarthritis (HOA) and their relationships with radiographic features. METHODS: A total of 446 patients with hand osteoarthritis (HOA; 233 with erosive HOA (EHOA) and 213 with non-EHOA) and 307 controls were evaluated. Demographic and clinical data from patients and controls were recorded based on medical records/clinical reports and an anamnesis of drug consumption. Posteroanterior radiographs of both hands were obtained from all HOA patients and were assessed using the Kellgren and Lawrence (K&L) and Kallman scoring systems. RESULTS: After adjustment for age, gender, and body mass index (BMI), HOA patients showed a significantly increased odds ratio (OR) for hypercholesterolaemia [OR 2.10, 95% confidence interval (CI) 1.39-3.16, p < 0.0005] and autoimmune thyroiditis (OR 4.85, 95% CI 1.77-13.29, p = 0.002), as well as for knee (OR 1.63, 95% CI 1.09-2.44, p = 0.018) and hip OA (OR 1.87, 95% CI 1.07-3.27, p = 0.029). No significant increase for systemic hypertension, ischaemic heart disease, and diabetes mellitus was found. Patients with EHOA and non-EHOA showed similar risks for the above-mentioned co-morbidities. A similar occurrence of clinical associations was also observed in patients with HOA alone and in those with generalized OA. No association between radiographic scores and clinical associations was observed. CONCLUSIONS: Patients with HOA present a direct association with hypercholesterolaemia (and autoimmune thyroiditis) but do not show increased ischaemic cardiovascular manifestations compared to controls. No significant association between radiographic scores and co-morbidities was found.

Objective To characterize the clinical and radiographic joint phenotype in erosive hand osteoarthritis (EHOA) and non-EHOA. Methods A total of 446 patients with HOA (233 with EHOA and 213 with non-EHOA) were evaluated. Demographic (sex and age at disease onset), clinical (body mass index and distribution of nodes), and radiographic features (Kellgren/Lawrence and Kallman's scores obtained from radiographs of both hands) from all patients were recorded. Results Patients with EHOA had a significantly earlier disease onset. Clinical and radiographic distribution of structural damage in the distal interphalangeal (DIP), proximal interphalangeal (PIP), and first carpometacarpal joints was similar in EHOA and non-EHOA. EHOA patients showed higher percentages of nodes and more severe radiographic scores; the more severe radiographic score of joints with nodes was due to both osteophytes and joint space narrowing (JSN). A direct correlation between osteophytes and JSN scores was observed. Central erosions (CE) were more prevalent in the DIP joints than in the PIP joints. Gull-wing pattern of CE was prevalent in the DIP joints, whereas saw-tooth pattern was prevalent in the PIP joints. Marginal erosions (ME) were present in 100% of EHOA patients and in 80% of non-EHOA patients. An ordinal correlation between the presence of ME and osteophyte score was found. Conclusion We found quantitative, but not topographic, differences in structural damage between EHOA and non-EHOA. Heberden's nodes, severe radiologic scores, and CE were concentrated in the second, third, and fifth DIP joints of both hands. ME were also present in the majority of non-EHOA patients.

Objective: IL-13/IL-4/IL-4R system has strong chondroprotective activity. We investigated polymorphisms in these genes as potential hand osteoarthritis (OA) susceptibility loci by performing a case-control association study. Methods: Eighteen common single nucleotide polymorphisms (SNPs) (nine in IL-4R, five in IL-4 and four in IL-13) were genotyped in 403 patients (380 females) with hand OA and 322 healthy controls (308 females). Results: Two SNPs (rs1805013 and rs1805015), mapping to the IL-4R gene, were associated with P-values of 0.0116 and 0.0305 respectively in the whole sample. As far as the non-erosive hand OA group (n= 159) is concerned, the significance level of association of SNP rs1805013 is increased. After correction for multiple testing (correction for the 54 tests) the significance was not retained.None of the IL-13 SNPs analyzed showed association with hand OA. Some of the analyzed SNP within the IL-4 gene showed significant association with hand OA only when considering subgroups of patients. With respect to the CMC1 OA group, two SNPs in IL-4 (rs2243250 and rs2243274) showed association with a P-value of 0.027 and 0.018 respectively. None of these associations remained after correction for multiple testing. Conclusions: The present study shows a trend to an association between non-erosive hand OA in Caucasian population and a genetic variant in the coding region of IL-4R gene. Our results, in keeping with previous data on hip OA, confirm the suggestion that IL-4/. IL-4R system plays a role in OA pathogenesis. Further confirmation studies on different populations are necessary. © 2010 Osteoarthritis Research Society International.