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Background IL-17-expressing FoxP3 regulatory T cells have been described, and their suppressive capacity has been questioned. An inflammatory environment seems to favor IL-17 secretion by regulatory CD4+CD25+FoxP3+ T cells. Objectives To assess the suppressive function and IL-17 producing capacity of CD4+CD25+CD127-FoxP3+ T cells in the synovial fluid of RA patients (RASFd). Methods Synovial fluid was drawn from 35 patients with established RA who were receiving methotrexate and low-dose oral prednisone. The frequency of CD4+CD25+CD127-FoxP3+ T cells was assessed by flow cytometry. Total CD4+ T cells, CD4+CD25+CD127- T reg cells and CD4+CD25- Tresp cells were isolated by Ficoll-Hypaque gradient, followed by sorting. After isolation, cells were stimulated for 5 hours with PMA+ionomycin or cultured for 5 days in flat-bottom 96-well plates coated with an anti-CD3 monoclonal antibody. Treg cell function was assessed using two different approaches: A.The regulatory function of natural proportions of Tregs was inferred by comparing the proliferative and cytokine responses of total CD4+ T cells (TCD4T) versus CD25+ depleted CD4+ T cells (CD4+CD25-T cells or Tresp cells); B. The per cell suppressor potency of Tregs was assessed in cocultures of isolated Tregs with Tresp, established at different Treg/Tresp ratios. Proliferation was determined by 3Hthymidine incorporation and CFSE dilution; cytokine secretion was measured by ELISA of culture supernatants. Results A high proportion of CD4+CD25+CD127- T cells was present in RASFd (mean ± SD, 21.1%±6.2), which is significantly higher than reported frequencies of this cell population in the peripheral blood of both RA and healthy subjects. These RASFd CD4+CD25+CD127- T cells expressed FoxP3 but did not express CD69. The proliferation rate, TNFα and IFNγ secretion were significantly higher for isolated Tresp as compared with TCD4T cells, indicating that natural proportions of Treg cells present in the synovial fluid of RA are funcionally suppressive. Surprisingly, TCD4T cells secreted higher amounts of IL-17 as compared with Tresp cells, although the difference did not reach statistical significance. On a per cell basis, RAPB Tregs were potent suppressors of Tresp proliferation, TNFα and IFNγ but not of IL-17 secretion; in fact IL-17 secretion did not decrease but was enhanced in the presence of increasing proportions of Treg cells. Isolated Treg cells did not proliferate or produce cytokines when cultured alone in anti-CD3 coated plates. However, in the presence of plate-bound anti-CD3 plus anti-CD28 and recombinant human IL-2, isolated Treg cells secreted significant amounts of IL-17 whereas no TNFα or IFNγ could be detected in supernatants. Conclusions CD4+CD27+CD127- FoxP3+ Treg cells present in the synovial fluid of RA patients are potent suppressors of Tresp proliferation, TNFα and IFNγ secretion, and at the same time produce significant amounts of IL-17. References Voo KS, et al. Proc Natl Acad Sci U S A. 2009;106:4793. Beriou G et al. Blood. 2009;113:4240. Wang T, et al. Ann Rheum Dis. 2015;74:1293. Komatsu N, et al. Nat Med. 2014;20:62. Yang BH, et al. Mucosal Immunol. 2016;9:444. Disclosure of Interest None declared

Objectives: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. Methods: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. Results: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. Conclusion: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.

To determine clinical and ultrasonographic predictors of joint replacement surgery across Europe in primary osteoarthritis (OA) of the knee.This was a 3-year prospective study of a painful OA knee cohort (from a EULAR-sponsored, multicentre study). All subjects had clinical evaluation, radiographs and ultrasonography (US) at study entry. The rate of knee replacement surgery over the 3-year follow-up period was determined using Kaplan-Meier survival data analyses. Predictive factors for joint replacement were identified by univariate log-rank test then multivariate analysis using a Cox proportional-hazards regression model. Potential baseline predictors included demographic, clinical, radiographic and US features.Of the 600 original patients, 531 (88.5%), mean age 67+/-10 years, mean disease duration 6.1+/-6.9 years, had follow-up data and were analysed. During follow-up (median 3 years; range 0-4 years), knee replacement was done or required for 94 patients (estimated event rate of 17.7%). In the multivariate analysis, predictors of joint replacement were as follows: Kellgren and Lawrence radiographic grade (gradeor =III vsIII, hazards ratio (HR) = 4.08 (95% CI 2.34 to 7.12), p0.0001); ultrasonographic knee effusion (or =4 mm vs4 mm) (HR = 2.63 (95% CI 1.70 to 4.06), p0.0001); knee pain intensity on a 0-100 mm visual analogue scale (or =60 vs60) (HR = 1.81 (95% CI 1.15 to 2.83), p=0.01) and disease duration (or =5 years vs5 years) (HR=1.63 (95% CI 1.08 to 2.47), p=0.02). Clinically detected effusion and US synovitis were not associated with joint replacement in the univariate analysis.Longitudinal evaluation of this OA cohort demonstrated significant progression to joint replacement. In addition to severity of radiographic damage and pain, US-detected effusion was a predictor of subsequent joint replacement.

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR- ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity >30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness >4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth >4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade >3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory ''flare'', such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory ''flare''.

OBJECTIVES To investigate the presence of soluble HLA class I (s-HLA) antigens in serum and synovial fluid (SF) from a large cohort of rheumatic patients. METHODS We studied clinical and analytical data and serum samples from 300 patients [122 patients with rheumatoid arthritis (RA), 38 with osteoarthritis or osteoporosis, 29 with seronegative spondyloarthropathies, 45 patients with other rheumatic diseases] and 66 healthy controls. In addition, we studied 25 paired samples of serum and SF from these groups of subjects. In RA patients, we examined whether the levels of s-HLA in serum and SF were related to the activity of the disease. RESULTS The mean concentrations of s-HLA molecules in serum were slightly higher in RA patients (1.2 microg/ml) than in the other four groups (1.08, 1.01, 1.09 and 0.94 microg/ml respectively). We found no correlation between serum s-HLA levels and any variable of inflammatory disease activity in RA patients. s-HLA molecules were found in SF and at levels that correlated with those found in serum (P=0.04; r=0.4). Furthermore, s-HLA levels were higher in SF from patients with RA (1.3 microg/ml) or crystal-induced arthritis (0.98 microg/ml) than in SF from those with osteoarthritis (0.38 microg/ml) (P

BACKGROUND Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. OBJECTIVE To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. DESIGN 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). SETTING 114 centers in 19 countries. PATIENTS 792 patients with active RA despite nonbiologic DMARD therapy. INTERVENTION Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. MEASUREMENTS Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)-defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. RESULTS Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. LIMITATIONS Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. CONCLUSION Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. PRIMARY FUNDING SOURCE Pfizer.

Background The anti-TNF monoclonal antibody Infliximab (Ifx), has proven effective in treating rheumatoid arthritis (RA), although in 40% of cases may fail, mainly due to immunogenicity. A good clinical response is usually associated with high serum drug levels; however, it is not clear why some patients have a faster drug clearance since the beginning of the therapy. Formation of immunocomplexes between antibodies to Ifx (ATI) and Ifx can increase drug clearance, leading to treatment failure. Objectives To analyze whether serum Infliximab trough levels (ITL) at the induction phase were related to Ifx disappearance and clinical outcomes at week (w) 54. The early development of immunogenicity as a related factor with low ITL was also investigated. Methods In this observational retrospective study ITL were measured from 66 RA patients from the prospective biological cohort of La Paz Hospital. Serum samples were taken at w2, w6, w14 and w22. Serum-dependent receiver operating characteristics (ROC) curves were used to establish the ITL value that better predicts the absence of Ifx at w54. ATI were measured by bridging ELISA and by an acid-dissociation method without drug interference IDK (Immundiagnostik®, Germany). Patients were grouped as ITLpos if they had detectable Ifx at w54 and ITLneg otherwise. Results ITLneg patients (n=25) had significantly lower levels at all time points than ITLpos (n=41). Based on ROC values ITL at w6 (4.44 μg/ml) had the best predictive value for disappearence of Ifx at w54 with a 70% sensitivity (95%CI 45.7–88.1), 95% specificity (95%CI 83.1–99.4) and positive likehood ratio of 14. Most patients in low disease activity or remission at w54 had at w6 ITL upper the predictive cut-off [20/44 (45%) upper cut-off vs 3/20 (15%) under cut-off p=0.02] and most EULAR responder at w54 had ITL upper the predictive cut-off at w6 [33/43 (77%) vs 10/21 (48%); p=0.08]. Treatment survival of patients with ITL upper 6w cut-off was longer: 5 years (1.6–5.0) vs 1.7 years (0.2–0.6); p=0.012. In the multiple logistic regression analysis, after adjusting for confounders (age, sex, body mass index, baseline DAS28, PCR, TNF and IL6) with ITL at w2 and at w6, the absence of Ifx levels at w54 was significantly associated with ITL under the cut-off at w2 (OR: 15.85; 95%IC 2.95–85.03; p=0.01), at w6 (OR: 86.64; 95%IC 6.58–1139.99; p=0.001) and no MTX use (OR: 12.26; 95%IC 1.83–82.22; p=0.001 for w2; OR: 6.9; 95%IC 1.04–45.84; p=0.04 for w6) Most patients with ITL under the cut-off at w6 were positive for ATI along the first year [15/20 (75%) under cut-off vs 5/44 (11%) upper cut-off, p Conclusions Low ITL at early stages (w2 and w6) are associated with the Ifx absence, the early drop-out of the treatment and the clinical outcome at w54, being the presence of ATI the main reason for the low early circulating drug levels. We also conclude that the cut-off value at w6 (4.44 μg/ml) provides the clinicians with a useful prognostic tool of treatment efficacy. Acknowledgement This work is partially funded by a non restricted grant from Pzifer and from Leti laboratories. Disclosure of Interest None declared

Background In most patients with axial spondyloarthritis (axSpA) achieving a clinical response after receiving standard dose of anti-TNF therapy, it seems possible to decrease anti-TNF dose without leading to flare of the disease. However, a minority of patients fails to this strategy and need to maintain standard dose of anti-TNF therapy in order to keep disease activity under control. Objectives To identify prognostic factors of flare after tapering anti-TNF therapy in patients with axSpA who achieve sustained clinical response with standard dose of this therapy. Methods This was a restrospective, observational study performed in a tertiary hospital. All patients with axSpA who had achieved sustained low disease activity for at least 6 months after receiving standard dose of a first anti-TNF drug and who had later decreased the dose of anti-TNF therapy were included. Low disease activity was defined as BASDAI 5mg/L) and/or delta-BASDAI ≥2. To identify possible predictors of flare, univariable and multivariable logistic regression analyses were employed including all variables described within the collected data as independent factors. Results Fifty-three patients with axSpA receiving a tapering strategy after achieving low disease activity were included. Characteristics for these patients are presented in table 1. Four patients interrupted anti-TNF due to adverse effect before ending the study. In total, 8/49 patients (16%) had a flare during the 2-year follow-up period. In the univaribale analysis, only the age (OR=1.06; p=0.05), BASDAI before tapering (OR=2.64; p=0.01) and ASDAS before tapering (OR=4.12; p=0.08) were significantly associated with the occurrence of flare. In the multivariable analysis, only the BASDAI before tapering remained statistically significantly associated with flare (OR=2.39; p=0.03). Conclusions In patients with axSpA and sustained clinical response to anti-TNF therapy, a tapering strategy leads to flare in less than 20% of patients. The value of BASDAI before tapering anti-TNF therapy predicts the occurrence of flare. This may help us to select the appropriate patients and moment to implement a tapering strategy in patients with axSpA. Disclosure of Interest None declared

Background CD19+CD24 high CD38 high B cells have been described to have a regulatory capacity and their frequency is altered in the peripheral blood of patients with various autoimmune diseases. The pathogenesis of AS is not well understood, and evidence suggesting the implication of either autoinflammatory or autoimmune mechanisms has been reported. In addition, increased frequencies of circulating B cells bearing a regulatory phenotype has recently been described in spondyloartrhitis (1). Objectives To study the frequency of circulating CD19+CD24 high CD38 high B cells (Breg) in patients with Ankylosing Spondylitis (AS), and test the regulatory capacity of this B cell subset. Methods Peripheral blood was drawn from AS patients naive for TNF blockers (AS/nb) (n=37) and healthy controls (HC) (n=37), that were matched with patients for age and gender. After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by flow cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting. Breg-depleted CD19+ B cells were obtained after total CD19+ B cells were depleted of CD19+CD24 high CD38 high B cells by cytometry in a FacsVantage sorter (Beckton Dickinson). Total CD19+ B cells or Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFNγ was determined by ELISA in culture supernatants. Results When compared with healthy controls, AS/nb patients demonstrated a significantly increased frequency of CD19+CD24 high CD38 high B cells (Breg). The frequency of circulating Breg was increased not only in AS/nb patients with high or very high disease activity (ASDAS-CRP) >2.1 but also in AS patients with low activity or no activity (ASDAS-CRP Conclusions An increased frequency of circulating CD19+CD24 high CD38 high B cells is observed in AS/nb patients, that is not related with disease activity. Functional in vitro studies confirmed that CD19+CD24 high CD38 high B cells are able to downmodulate B cell pro-inflammatory cytokine secretion. References Cantaert T, Doorenspleet ME, Francosalinas G, Paramarta JE, Klarenbeek PL, Tiersma Y, van der Loos CM, De Vries N, Tak PP, Baeten DL. Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis. Arthritis Rheum. 2012;64:1859–68. Disclosure of Interest None declared

Background Temporal Arteritis (TA) is the most common systemic vasculitis in adults. Usually, the diagnosis is based on the American College of Rheumatology (ACR) classification criteria published in 1990 based on the clinical history, physical examination, laboratory information and histological findings in the biopsy. However, according to the literature, the biopsy can be negative in up to 68% of patients with TA and without it the predictive value diminishes considerably. Objectives Assess the value of Doppler Ultrasonography for the diagnosis of TA, compared with ACR criteria and biopsy, using the definitive clinical diagnosis of the patient as gold standard. Methods A retrospective observational, descriptive and analytical study was made, reviewing the clinical history of the patients who had an ultrasound scan of the temporal artery performed in our hospital on suspicion of TA. The standard exploration consists of the bilateral examination of the temporal superficial artery, with its common trunks and the frontal and parietal branches. In the case of diagnostic doubt, the exploration is extended to the occipital arteries and/or axilares. The ultrasound scans were realized and reported by the same person to avoid bias. The variables registered were age and sex, the presence or absence of ACR criteria, VSG value, the final diagnosis and the results of the biopsy and the ultrasound examination as well as the number of affected branches. The statistical analysis was realized by means of the software program SPSS Statistics version 20.0. Results Of the 451 patients studied, 399 were women and 52 men (88.5% vs 11.5%), with a mean age of 81. Two hundred fifty six patients (58,8%) had a definite diagnosis of TA while 195 (43,2%) presented other diagnoses. Two hundred forty patients (55.79%) fulfilled ACR criteria and 211 did not (46,78%). Of the 166 biopsies, 54 (32,53%) were positive. The validity (sensitivity and specificity) and security (positive predictive value [PPV], negative predictive value [NPV], Likelihood Ratio [LR] + and LR -) of diagnostic tests used were as follows: Conclusions Doppler Ultrasonography shows great validity and safety as a diagnostic test of TA, being in addition, a cheaper and less harsh technique than the biopsy.For this reason its use in clinical practice should be considered a diagnostic option of the first line in the diagnosis of this disease. Disclosure of Interest None declared

Background Temporal Arteritis (TA) is a vasculitis characterized by systemic and ischemic symptoms that concern fundamentally supraaortic blood vessels. The neurological clinic can be expressed as: headache, visual alterations, affection of cranial nerves, transient ischemic attack (TIA) or ischemic stroke in carotid or vertebrobasilar territory. The ocular affection is the most frequent but other neurological ischemic affections, not retinals, are not rare but they often occur unnoticed and are attributed to atherosclerosis given the age of the patients. Being a treatable and preventable process, there is an opportunity to improve the diagnosis of this affection. Objectives Assess the vascular events of supraaortic blood vessels, ocular vessels and non ocular vessels in our vasculitis surgery. Methods A retrospective study was carried out on the clinical history of the patients sent to our vasculitis surgery on suspicion of TA. The diagnosis of arteritis or nonarteritic neurological affection was realized in agreement with usual clinical criteria. The variables registered were age and sex, cardiovascular risk factors (CVR), clinical manifestations,VSG and PCR values, the final diagnosis and the results of the biopsy and the ultrasound examination, as well as the number of affected branches, brain TAC and MRI. The statistical analysis was realized by means of the software program SPSS Statistics version 20.0. Results Of the 163 patients studied, 112 were women and 51 men (31,3% vs 68,7%). One hundred thirteen patients (59,32%) had definite diagnosis of TA while 50 (30,68%) presented other diagnoses. Of the total of the patients, 59 (24 men and 35 women) presented neurological clinic: diplopia 10, loss of vision 48, TIA 7 and ACVA 4. Of these 42 were diagnosed with arteritic neurological affections (secondary to TA): 6 diplopia, 35 loss of vision, 4 TIA and 2 ACVA. Among the patients with nonarteritic and arteritic neurological events no differences were found for sex, VSG, PCR, blurry vision, fever, loss of vision, diplopia, TIA, ACVA, CVR, smoking and atrial fibrillation (AF): there was only significant differences for age. The analysis of the patients diagnosed with TA, withand without neurological events, appear in the table. Conclusions Non ocular central neuroischemic events are frequent and affect 10,62% of the patients with TA. Among the patients with TA the neuroischemic risk associates to being a male, advanced age, a greater number of affected branches in ultrasound examination and to the presence of headache. Disclosure of Interest None declared

Background Sjogren syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands resulting in clinical symptoms of keratoconjunctivitis sicca and xerostomia. Recent studies have shown that salivary gland ultrasonography (SGUS) is a valid tool to evaluate the involvement of major salivary glands in SS. Objectives To assess the utility and accuracy of the USGS for diagnosis of SS. Methods Single-center experimental study in a cohort of patients with suspected SS in whom a salivary gland biopsy (SGB) would be performed as requested by their usual physician. SGUS examination of the parotid and submandibular salivary glands was preformed prior to the realization of minor salivary gland biopsy. Changes in the echostructure of the glands were scored according to the scoring system of de Vita et al., which mostly focuses on the inhomogeneity of gland tissue with scores ranging from 0 to 3 (0: homogenous glands, 1: isolated hypoechoic areas, 2: scattered hypoechoic areas with variable size, not uniformly distributed, and/or to multiple punctate or linear non-shadowing densities and 3: large round or confluent hypoechoic areas, and/or to linear densities, and/or to multiple cysts or multiple calcifications). The SGB was considered as Gold standard. The definitive diagnosis of SS was made according to the AECG criteria. Results From a sample of 24 patients with suspected SS, SGUS was performed in 20 patients before the SGB. All the patients were women with a mean age of 58±14. Eleven patients (46%) fulfilled AECG criteria, 4 (17%) did not met criteria and in 9 of them (37%) was not possible to classify because of insufficient data (at least two unregistered criteria). Eleven patients (55%) had a normal SGUS while 9 (45%) had some degree of changes in the gland9s echostructure. In the group of patients who met AECG criteria, four (36%) had a negative biopsy, four (36%) positive biopsy and 3 (28%) had nonspecific biopsy. Of the 9 patients with an uncertain diagnosis for lack of data, 7 (78%) had a nonspecific biopsy. 5 patients (56%) with changes in the SGUS met AECG criteria. Of the 6 patients with positive biopsy for SS, 4 (67%) had ultrasound abnormalities. Of the 7 patients with pathological salivary scintigraphy, 5 (71%) had alterations in USGS. Taking biopsy as the gold standard, the sensitivity of the SGUS was 100%, specificity was 68.75%, PPV 44.4% and NPV of 100%; the sensitivity of scintigraphy was 80%, specificity was 44%, PPV 44% and NPV 44%. Considering the scintigraphy as the gold standard, sensitivity of ultrasound was 71.4%, specificity was 100%, PPV 100% and NPV 60%. As limitations of this study is important to remark that these are preliminary results from a small sample in early stages of the disease. Conclusions Our findings suggest the potential of SGUS as a diagnostic tool for distinguishing SS. Although data is preliminary we found high sensitivity and NPV of SGUS compared to biopsy and high specificity of SGUS compared to scintigraphy. Disclosure of Interest None declared

Background The anti-tumor necrosis factor (anti-TNF) therapy has shown to be effective in rheumatoid arthritis (RA). Recent publications have shown the association between drug levels (DL) and clinical response to the anti-TNF therapies. For now it is not clear if the DL monitoring to the 1st anti-TNF in patients who discontinued due to inefficacy, can be useful to evaluate the clinical efficacy to the 2nd anti-TNF. Objectives To evaluate in a RA cohort (who stopped to the 1st anti-TNF due to inefficacy), the influence of the presence/absence of DL [infliximab (Ifx) y adalimumab (Ada)] at discontinuation, on the clinical response to the 2nd anti-TNF during the 1st year of therapy. Methods Seventy seven out of 182 RA patients who discontinued the Ifx or Ada therapy were recruited. All these patients dropped out the first anti-TNF due to inefficacy and switched to a 2nd anti-TNF (48 patients: 2 with Ifx, 4 with Ada, 40 with etanercept and 2 with certolizumab) or other biologics (OB) different to anti-TNF (29 patients: 17 with rituximab, 6 with tocilizumab and 6 with abatacept). Clinical activity was measured by DAS28 and clinical improvement by Delta-DAS28 adjusted to baseline clinical activity (baselineDAS-DAS (24weeks or 52weeks)/baselineDAS) at baseline, 24 weeks (24w) and 52 weeks (52w). DL were measured prior to drug administration at 24w and 52w by ELISA. Results Of the 77 RA patients, 82% (63/77) were women and the mean disease duration was 21±13 years. At the end of the 1st antiTNF, 54/77 (70%) had undetectable DL and 23/77 (30%) had detectable DL. At w24 of the 2nd biologic, patients treated with OB tended to be less active than patients treated with a 2nd anti-TNF but these differences were not significant at w52 ( DAS28 at w24: 3.5±1.3 with OB vs 4.1±1.1 wirh 2nd anti-TNF, p=0.053; Delta-DAS28 at w24: 0.3±0.3 with OB vs 0.2±0.3 with 2nd anti-TNF, p=0.326; DAS28 at w52: 3.3±1.2 with OB vs 3.8±1.1 with 2nd anti-TNF, p=0.166; Delta-DAS28 at w52: 0.3±0.2 with OB vs 0.2±0.3 with 2nd anti-TNF, p=0.501). Patients with undetectable DL to first anti-TNF treated with a 2nd anti-TNF had better clinical response during the first year of therapy ( DAS28 at w24: 3±1.1 with non DL vs 4.3±1.2 with DL, p=0.004; Delta-DAS28 at w24: 0.3±0.3 with non DL vs 0.2±0.3 with DL p=0.074; DAS28 at w52: 2.9±1.1 with non DL vs 4±1.2 with DL, p=0.015; Delta-DAS28 at w52: 0.4±0.2 with non DL vs 0.2±0.3 with DL, p=0.210). However, no differences in the clinical activity were observed between patients with undetectable or detectable DL who switched to OB ( DAS28 at w24: 4.4±1.4 with non DL vs 3.8±1 with DL, p=0.247; Delta-DAS28 at w24: 0.2±0.2 with non DL vs 0.2±0.2 with DL, p=0.382; DAS28 at w52: 4.1±1.2 with non DL vs 3.5±0.7 with DL, p=0.122; Delta-DAS28 at w52: 0.2±0.2 with non DL vs 0.3±0.1 with DL, p=0.376). Conclusions In our cohort of RA patients with inefficacy to the 1st anti-TNF, a high proportion of patients discontinued the therapy with undetectable DL. The DL monitoring during the 1st anti-TNF seems to be a useful tool to define what patients have a better clinical response to the 2nd anti-TNF, although this effect does not influence on those patients who switch to OB. Disclosure of Interest None declared

Objective To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). Methods 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results A total of 39 756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. Conclusions Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Osteoarthritis is the most common articular degenerative disease and can be classified as primary or secondary. The last one must be excluded in the context of a young adult. Optimal management requires early diagnosis and awareness of the risk factors (more importantly «modifiable» ones) that can affect the prognosis. The authors present a case of a young man who complaint about mechanical groin pain because degenerative changes on hip joint. After patient assessment it was encountered ultrasonographic typical images of gout in the context of asymptomatic hyperuricemia.

Ten recommendations for the use of methotrexate were recently developed, based on published data and expert opinion in the 3E initiative1 (table 1). Clinical guidelines may induce small improvements both in processes and in the outcomes of care.2 However, if recommendations are to have effect, it is necessary after they have been published to facilitate their dissemination.3 In order to improve the implementation of these recommendations in daily practice, an initiative was performed in 2008 according to published methodology4 which aimed …

To evaluate the evolution of musculoskeletal ultrasonography and its role in rheumatological practice by comparing recent casuistics of the ultrasonography exams performed at the Rheumatology Department of University Hospital La Paz -Madrid with the exams performed before 2003.Revision of the ultrasonographies made between January 2007 and June 2008 and comparison with the exams performed between 1998 and 2003.In the recent casuistics, that included 1,000 exams, anatomic ultrasonography represents 45.9% in contrast to 100% of the ultrasonographies preformed before 2003. The indication for the remaining 54.1% were: diagnosis of arthritis 16.3%, evaluation of inflammatory activity 6.8%, evaluation of enthesis 6.3%, study of temporal arteries 12.5% (9.7% for suspected temporal arteritis and 2.8% for disease monitoring); differential diagnosis of gout or chondrocalcinosis 2.2%, diagnosis of sacroiliitis 1.2%, diagnosis of carpal tunnel syndrome 1.5% and sonographic-guided procedures 7,3%.At the present time, the anatomic ultrasonography represents 45.9% of all ultrasonographies in contrast to what happened before 2003. Technological advances and the progress in science promote the evolution of ultrasonography from an anatomical imaging tool to a more clinical, diagnostic, monitoring and therapeutic profile.

To determine the effect of changing from etanercept or methotrexate monotherapy to etanercept plus methotrexate combination therapy on radiographic progression in rheumatoid arthritis (RA) patients.Patients enrolled in this 1-year open-label study previously completed a 3-year blinded study in which they received methotrexate or etanercept monotherapy or the combination of both. All patients received the combination of etanercept 25 mg subcutaneously twice weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint was a change in modified total Sharp score (TSS), as assessed by blinded readers.At baseline, patients previously receiving methotrexate monotherapy (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68) had moderate disease activity levels (mean disease activity score (DAS) of 2.6 and 2.5, respectively), whereas patients previously receiving combination therapy (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of etanercept to methotrexate monotherapy resulted in a significant reduction in radiographic progression (p0.05). Mean TSS changes in the previous year versus the current year were +1.79 versus +0.25 for the etanercept-added group (p0.05); +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24 for the combination group (NS).In these RA patients with on average moderate disease activity despite previous methotrexate monotherapy, combination treatment with etanercept and methotrexate inhibited radiographic progression and improved radiographic outcomes. These data, in conjunction with the previously published clinical data, support the use of combination therapy in RA patients with moderate disease activity.

Contains fulltext : 69269.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.

Background Anti-TNF therapy is successful for achieving low disease activity or clinical remission in patients with axial spondyloarhritis (axSpA). Nevertheless, this therapy has not clearly shown to slow or inhibit radiographic progression in these patients. Based on this, it is unclear what therapeutic attitude should be adopted once remission has been achieved in patients with axSpA. Objectives To evaluate if anti-TNF tapering is efficacious for maintaining remission or low disease activity (LDA) in patients with spondyloarthritis (axSpA). Methods A systematic literature review until August 2014 was performed using Medline, EMBASE and Cochrane databases. The research question was formulated according to the PICOS method: Population (axSpA patients); Intervention (anti-TNF dose tapering); Outcome (flare or change on disease activity); and Setting (longitudinal studies with at least 6 months of follow up after dose adjustment). Data was extracted using a form developed for this specific purpose. Results are shown as median (range) and relative frequencies in percentages. Results In total, 8 studies from 763 citations were included. All studies included patients with ankylosing spondylitis from single centers and no study included patients with non-radiographic axSpA. The study design was retrospective cohort (n=3), prospective cohort (n=3), non-randomized trial (n=1) and RCT (n=1). In these studies, patients receiving standard doses of anti-TNF therapy who were in remission (BASDAI Conclusions Published data indicates that anti-TNF therapy tapering is successful in maintaining remission or LDA during at least one year in a high number (>50%) of patients with AS. Further data are required to identify which patients with axSpA are included within this group. Disclosure of Interest None declared

Background Current treatment strategies in rheumatoid arthritis (RA) aim to remission or low disease activity. Composite indexes used in clinical practice to assess RA disease activity have good correlation with joint ultrasonography (US), but some patients clinically classified as in remission have subclinical synovitis which cannot be detected by clinical examination or acute phase reactants. We have previously shown that calprotectin correlates with disease activity (1) but it is not known if can be useful to detect patients who have achieved the therapeutic target in whom active synovitis is still present. Objectives To investigate in RA patients who have achieved the therapeutic target (remission or low disease activity) if plasma calprotectin levels can be useful to classify patients in clinical remission or low disease activity using US as gold standard. Methods RA patients taking DMARD or biological agents in clinical remission or low disease activity (DAS28-ESR Results 82 patients, age 53.9±12.1 years, 69 (84%) female with a disease duration of 7.5±3.9 years were studied. 72 (87%) and 73 (89%) were anti-CCP and RF positive respectively. Mean DAS28 was 2.47±0.5 and 43 (52%) were in remission by DAS28 (DAS28 Calprotectin levels correlated with SDAI (r=0.34; p=0.001) and CDAI (r=0.34; p=0.002), but not with DAS28 (r=0.17; p=0.1). No correlation was observed between calprotectin and ESR (r=-0.08; p=0.9) or CRP (r=0.02; p=0.8). A significant correlation was found between Calprotectin levels and US PD in 42 joints (r=0.23; p=0.03), that was not found between Calprotectin and SH. If we consider remission the absence of joints with PD signal, no differences were found by DAS28 between patients in remission and low disease activity (p=0.3), although differences were present by SDAI (p=0.007) and CDAI (p=0.003). No differences in calprotectin levels were found between patients in US remission vs no US remission (0.9±0.7 vs 2.6±7.4; p=0.4). Conclusions In patients in low disease activity or remission, calprotectin levels correlate with SDAI and CDAI but not with DAS28-ESR. Although, calprotectin levels correlate with the number of joints with PD signal it was not possible to accurately classify patients in US remission. References Garcia-Arias M. Calprotectin in rheumatoid arthritis: association with disease activity in a cross-sectional and a longitudinal cohort. Mol Diagn Ther. 2013 Feb;17(2):49-56 Disclosure of Interest S. Garcia-Carazo Grant/research support from: This work was supported by an unrestricted grant from UCB, E. De Miguel: None declared, A. Martinez-Feito: None declared, D. Pascual-Salcedo: None declared, M. Arribas-Arribas: None declared, T. Jermann: None declared, M. Diaz: None declared, E. Martin-Mola: None declared, A. Balsa Grant/research support from: This work was supported by an unrestricted grant from UCB

Background CD19+CD24 high CD38 high B cells have been described to have a regulatory capacity and their frequency is altered in the peripheral blood of patients with various autoimmune diseases. Objectives To determine the frequency of circulating CD19+CD24 high CD38 high B cells in patients with RA, and establish a correlation with clinical parameters. Methods Peripheral blood was drawn from RA patients treated with non-biological DMARDs (n=48), RA patients treated with anti-TNFalpha drugs (n=15) and healthy controls (n=63) that were matched with patients for age and gender. After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by flow cytometry. Results A decreased frequency of CD19+CD24 high CD38 high B cells was apparent in in ACPA+ but not ACPA- RA patients, and this was observed not only in patients treated with non-biological DMARDs but also in patients receiving anti-TNFalpha drugs. In addition, the frequency of CD19+CD24 high CD38 high B cells showed a significant negative correlation with ACPA titers (r = -0.43, p=0.023). In contrast, no correlation was found between the frequency of circulating CD19+CD24 high CD38 high B cells and either rheumatoid factor titres or disease activity as determined by the DAS28 score. Conclusions A decreased frequency of CD19+CD24 high CD38 high B cells is observed in ACPA+ but not ACPA- RA patients treated with either nonbiological DMARDs or anti-TNFalpha drugs, that is related with ACPA titres but not with rheumatoid factor titres or disease activity. Disclosure of Interest None declared

Background In patients with axial spondyloarthritis (axSpA), anti-TNF therapy is successful for clinically improving signs and symptoms of the disease. However, there is no clear evidence of the capability of this therapy to slow or inhibit radiographic progression. Based on this, it is unclear whether or not this treatment should be indefinitely sustained once the clinical goal is achieved in these patients. Objectives To evaluate if discontinuation of anti-TNF therapy is successful to maintain clinical response in patients with axSpA. Methods A systematic literature review until August 2014 was performed using Medline, EMBASE and Cochrane databases. The research question was formulated according to the PICOS method: Population (axSpA patients); Intervention (discontinuation of anti-TNF); Outcome (flare); and Setting (longitudinal studies with at least 6 months of follow-up after anti-TNF discontinuation). Flare was assessed according to the definition employed by each study, usually BASDAI ≥4 & Physician9s assessment ≥4 or ΔBASDAI ≥2. Exclusion criteria were: less than 12 weeks on anti-TNF treatment before discontinuation or no clinical improvement achieved during the treatment. Data was extracted using a form developed for this specific purpose. Results are shown as median (range) and relative frequencies in percentages. Results Five studies from 763 citations were included, with a total of 215 patients (76% AS and 24% nr-axSpA). The study design was: prospective observational studies following participation on a RCT (n=4) and RCT (n=1). In these studies, patients receiving standard doses of an anti-TNF drug discontinued this therapy and were followed in order to assess the appearance of flare. Discontinued therapy was etanercept (n=3), infliximab (n=1), and adalimumab (n=1). The characteristics of the studies were: total number of patients 42 (24-111) and follow-up period after discontinuation 52 (36-52) weeks. Baseline characteristics of patients were: age 39 (37-40) years old, 68% (45-77) males, disease duration 8 (3-15) years, 92% (67-100) HLA-B27+, and time receiving anti-TNF therapy before discontinuation 11 (2.5-36) months. Median (range) percentage of patients developing flare during the follow-up period was 79% (69-100). Specifically, these percentages and periods were as follows: 100% (within 36 weeks), 98% (within 48 weeks), and 69%, 79% and 79% (within 52 weeks). Median (range) time to flare was 16 (6-24) weeks. Furthermore, the 4 observational studies following a RCT re-treated patients with flare using the same anti-TNF. Overall, similar response to the one achieved at the beginning of the RCT was observed for most clinical outcomes. Conclusions Published data indicates that discontinuation of anti-TNF therapy in patients with axSpA leads to the appearance of flare within a few months in most cases. However, most of the published evidence is based on studies including patients with established disease. Therefore, it still remains to be evaluated whether or not this high frequency of flares is observed in patients with shorter disease duration. Disclosure of Interest None declared

Background Biological agents against tumor necrosis factor (Anti-TNF) have revolutionized the treatment of Rheumatoid Arthritis (RA). Recent studies assess the possibility of reducing the dose or increase the interval of administration of biologics (optimization strategy: OS) in patients with at least sustained low disease activity (LDA) without relevant clinical worsening. One of the questions raised is whether the use of OS could increase the incidence of anti-drug antibodies (ADA) appearance with the consequent loss of efficacy. Objectives To evaluate the influence of the OS in a cohort of RA patients at least in LDA on the clinical activity (DAS28), incidence of flares, serum drug levels and ADA appearance. Methods A retrospective observational study of a cohort of RA patients in LDA or remission (measured by DAS28 Results Of the 54 patients, 77.8% were women. Mean age was 60.2±12 years. The 79.6% (43) were antiCCP and FR positive. Regarding concomitant treatment 35 patients (64.8%) received methotrexate at baseline, 25 (46.3%) other DMARDs and 23 (42.6%) prednisone. Twenty-seven (50%) were treated with Ada, 16 (29.6%) with Etn and 11 (20.4%) with Ifx. No significant differences were observed in the control of DAS28 between the pre-visit and pos-visit in every Anti-TNF (Ada: 2,13±0,12 pre-visit vs 2,42±0,18 pos-visit, p=0,064; Ifx: 2,32±0,11 pre-visit vs 2,19±0,18 pos-visit, p=0,799; Etn: 2,36±0,12 pre-visit vs 2,93±0,20 pos-visit, p=0,056). There was no statistically a significant increase in CRP levels between pre and post visits in any Anti-TNF (Ada: p=0,629; Ifx: p=0,799; Etn: p=0,796). Nineteen (35.2%) developed flares during the follow-up (14 patients had one flare and 5 had 2 flares). All patients were negative for ADA at the pre-visit, 5 (9.25%) were positive at pos-visit associated with flares. Sixteen (29.6%) out of the 19 patients with flare required to shorten the interval or increase the dose to control DAS28. A statistically significant decrease was observed in drug levels between the pre-visit and post-visit in patients treated with Ada and Etn (Ada: 5127.88±1542.65 pre-visit vs 1200.29±276.52 pos-visit, p=0.003; Etn: 2794.46±367.07 pre-visit vs 1359.38±375.121 pos-visit, p=0.023). Conclusions OS seems to be feasible in RA patients in LDA treated with Anti-TNF, reducing the amount of drug administered with low incidence of ADA and without impact on clinical and serological markers such as CRP. In most patients with flares, the clinical activity appears to be controlled by shortening the interval of administration without increasing the therapy discontinuation. Disclosure of Interest B. Paredes Grant/research support from: This study has received unrestricted grants from Pfizer

OBJECTIVES: To develop evidence based recommendations for the management of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. RESULTS: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. CONCLUSION: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.

BACKGROUND: Osteoporotic fractures remain a major public health problem. Currently available osteoporosis therapies significantly reduce the risk of fractures, but up to 50% of patients have an inadequate clinical outcome to therapy. AIM: To describe the clinical and quality of life (QOL) of a study population meeting a proposed definition of inadequate clinical outcome to osteoporosis therapy, recruited for the Observational Study of Severe Osteoporosis (OSSO). DESIGN: Cross-sectional, observational study. METHODS: Post-menopausal women with osteoporosis (n = 2314) were divided into Group 1 (those who had previously experienced a fragility fracture despite osteoporosis drug therapy for at least 12 months) (n = 1309, 57%), or Group 2 (those who had previously discontinued osteoporosis drug therapy due to non-compliance or side-effects) (n = 1005; 43%). Baseline clinical characteristics, quality of life (QOL) and osteoporosis/falls risk factors were analysed. RESULTS: The overall population had low BMD (mean +/- SD T-score at lumbar spine -3.1 +/- 1.1), and risk factors for fracture such as previous fractures (67.8%), family history (15.1%), and prolonged glucocorticoid use (17.5%). QOL was poor: total QUALEFFO and EQ-5D scores were 46.8 +/- 18.7, and 0.50 +/- 0.33, respectively. Patients in Group 1 had higher age and body mass index, fewer hours of exercise, more previous fragility fractures and falls, and poorer QOL scores. DISCUSSION: Our definition of inadequate clinical outcome from osteoporosis drug therapy identifies a severe osteoporosis cohort with poor QOL and increased fracture risk. Using such a definition may lead to earlier recognition of inadequate clinical outcome to osteoporosis therapy, and improved interventions and results.

Objective: To evaluate the level of acceptability of the EULAR recommendations for the management of knee osteoarthritis (KOA) in practice. Methods: A questionnaire was sent to general practitioners, rheumatologists, rehabilitators, and orthopaedic surgeons in five European countries (France, Spain, Belgium, Switzerland, Italy). Practitioners were asked to give their opinion on the 10 EULAR recommendations and on 23 treatment modes for KOA. Practitioners' opinions were compared with those of the expert task force involved in the development of these recommendations. Results: The overall response rate was 10.4% (4204 replies). Results were similar across countries and specialties. Of the 23 treatment modes proposed, only joint lavage and intra-articular (IA) corticosteroid injections were more strongly recommended by the expert task force than by the responders as a whole, while the opposite was true for spa therapy. Principal component analysis showed: (1) some practitioners preferred "hard line" treatments (surgery, IA injections, or non-steroidal anti-inflammatory drugs (NSAIDs)); (2) there was a difference between those prescribing pharmacological (paracetamol) or non-pharmacological measures with low iatrogenicity (exercises, sticks, education), and those prescribing less well validated treatments closer to "alternative" medicine; (3) each specialist tended to advocate modes that they were most familiar with: rheumatologists were more likely to recommend IA injections and NSAIDs; orthopaedic surgeons, surgical procedures; rehabilitators, education and all non-pharmacological modes; general practitioners, spa therapy and opioids. Conclusions: A multidisciplinary approach is optimal in the management of this chronic disease with its variable course.

To determine whether the presence of radiographic erosions at disease onset in patients with early rheumatoid arthritis (RA) is associated with clinical, serological, or genetic factors of poor outcome and whether patients with erosions only in the feet have a different pattern of presentation.Sixty one patients with early RA (6 months of evolution) were studied. Clinical evaluation and serological, radiological, and genetic studies were performed at disease onset and after one year.Forty one (67%) patients showed erosions in their hands or in their feet, or in both. Subjects with erosive RA had a higher number of swollen joints (SJN; 9 (SD 6) v. 6 (3), p=0.008), and rheumatoid factor (RF) positivity was more common (80% v. 50%, p0.02) than those without erosions. Seven (17%) of the 41 patients in the group with erosions had erosions only in their feet. This group had a longer duration of morning stiffness (120 (60) v. 72 (52) min, p0.005), better patient's global assessment of general health (34 (22) v. 57 (25), p0.05), and lower erythrocyte sedimentation rate (32 (22) v. 60 (30) mm/1st h, p0.05) than the rest of the subjects with erosions, and none of them was in remission after one year. Remission after one year was related to a lack of cortical damage at onset and RF negativity.Radiological damage at disease onset is associated with a worse clinical presentation and RF positivity, which are markers of poor outcome. There is a subgroup of patients, with erosions only in their feet, whose clinical presentation is less aggressive. To identify these cases of early erosive RA, radiographs of the feet should be obtained routinely.

Background Follicular helper T cells (Tfh), a CD4 T helper subset localized in lymphoid organs, help B cell differentiation and function. Circulating CD4 T cells expressing CXCR5 together with ICOS and/or PD-1 are considered as counterparts of Tfh, can function as B cell helpers, and can be subdivided into three subpopulations based on the expression of CCR6 and/or CXCR3: CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2, as opposed to Tfh-Th1, seem to display functional properties of Tfh cells. An altered proportion of these subpopulations has been associated with autoimmune diseases. Objectives To study the frequency of circulating Tfh and Tfh cell subsets together with the frequency of circulating plasmablasts (CD19+CD20-CD27+CD38high B cells) in patients with Ankylosing Spondilytis (AS). Methods Peripheral blood was drawn from healthy controls (n=50), AS patients receiving NSAIDs (n=25) and AS patients treated with TNF blocking agents (n=25). After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, ICOS, PD-1, CCR6, CXCR3, CD19, CD20, CD27, and CD38, and examined by flow cytometry. The percentages of CXCR5+CXCR3+ CCR6- (Tfh-Th1), CXCR5+CXCR3- CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh/Th2) cells were calculated after gating for CD3, CD4 and CXCR5+. The percentage of CD20-CD38high cells was calculated after gating for CD19+ and CD27+. Results The frequency of circulating CXCR5+ cells gated for CD4+ T cells was not different among the studied groups. In contrast, AS patients receiving NSAIDs but not those on TNF blockers, demonstrated a decreased frequency of CD4+CXCR5+ICOS+ PD-1+ cells. Furthermore, in AS patients receiving NSAIDs, the frequency of Tfh-Th1 cells was significantly increased and the frequency of Tfh-Th17 and Tfh-Th2 cells was significantly decreased as compared with controls. Subsequently, the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1 was decreased in these patients. At the same time, the frequency of circulating plasmablasts was decreased in AS patients on NSAIDs. Interestingly, there was a significantly positive correlation between the percentage of circulating plasmablasts and the frequency of CXCR5+ICOS+PD-1+CD4+ T cells. In addition, the frequency of circulating plasmablasts showed a positive correlation with the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1. Conclusions AS patients treated with NSAIDS, but not those receiving TNF blockers, demonstrate a decreased frequency of circulating Tfh counterparts (CXCR5+ICOS+PD-1+CD4+ T cells) and altered proportions of circulating Tfh subpopulations, with underrepresentation of subsets bearing a phenotype associated with B cell helping capacity. At the same time, a decreased proportion of circulating plasmablasts is apparent in AS patients treated with NSAIDs. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1753

To validate a Spanish version of the Northwick Park Neck Pain Questionnaire (NPQ) and to prove its usefulness in clinical practice.We studied 58 patients with non-inflammatory neck pain of more than 4 months duration. A blind back translation of the NPQ was made, and the resulting back-translation version was then compared with the original. The NPQ comprises 9 questions with 5 statements of increasing difficulty. Patients completed the questionnaire 3 times: on their initial assessment; 8-10 days later (test-retest); and after physiotherapy treatment 3 months later. Neck pain was assessed by a visual analogue scale (VAS).Fifty-three patients completed the questionnaire (90%). There was a good intra-class correlation between the test-retest NPQ (r = 0.63), indicating good agreement. For each of the 9 sections, agreement ranged from r = 0.43 to r = 0.85, p0.05 in all cases. Correlation with the VAS was also good, between r = 0.51 (test) and r = 0.74 (retest) (p0.05 in all cases). Pain measured by the VAS increased according to the NPQ score, grouped by percentages (p = 0.003). The mean scores for each section increased with that of the intensity of pain, in most sections showing good internal consistency. Pain and the NPQ score improved after treatment (56.1 +/- 20.2 to 29.9 +/- 20.1, p = 0.0001 and 45.9% +/- 12.7% to 28.9% +/- 15.3%, p = 0.0001 respectively), as did all the other items except for driving (p0.05).The Spanish version of the NPQ is a feasible, reliable and valid instrument to measure pain in Spanish-speaking patients with chronic neck pain.

Antiperinuclear factor (APF) is an autoantibody detected in50% of patients with rheumatoid arthritis (RA); it shows a specificity of roughly 90%. We investigated the possible role of APF as a prognostic marker in RA.A series of 103 patients with RA who fulfilled the 1987 American College of Rheumatology criteria (88 women and 15 men; mean age 55.5 yrs, mean disease duration 9 yrs) were prospectively followed. Sixteen variables were assessed in each patient at inclusion and over a 3 year period. APF was determined by indirect immunofluorescence assay using human buccal mucosal cells as substrate. APF assays were done at entry and at the end of followup without knowledge of the clinical status of the patients. Mann-Whitney U, chi-squared tests, variance analysis, and kappa index were used for statistical analysis.Eighty of 103 patients completed followup. APF was detected in 40 of 80. At inclusion, APF correlated with the visual analog scale (VAS) of pain (p = 0.02). However, patients who showed APF positivity at entry had a less favorable course than APF negative individuals, as shown by a worse VAS of well being (p = 0.01), Ritchie index (p = 0.01), number of painful joints (p = 0.03), grip strength (p = 0.01), C-reactive protein (p = 0.04), and Health Assessment Questionnaire score (p = 0.03) at the end of the study. In addition, APF positive patients showed a worse radiological course (p = 0.03).Our results suggest APF is a possible marker of poor prognosis in RA.

SUMMARY Objective. To study prospectively whether serum and urinary nitrate levels are related to lupus activity. Methods. Fifty patients with systemic lupus erythematosus (SLE ) were studied prospectively for 2 yr. Every 4 months, the SLE Disease Activity Index (SLEDAI ) was administered to the patients, and blood and 24 h urine samples were obtained; 88 healthy controls were also studied. Nitrate levels were measured by the Greiss method. Statistical analyses were performed using standard parametric and non-parametric tests, and analysis of serial measurements. Results. Twelve patients suVered infections, 12 active nephritis and 17 episodes of non-renal activity. By analysis of serial measurements, serum and urinary nitrate levels did not correlate with SLEDAI. C-Reactive protein (CRP) levels, presence of infection and creatinine clearance weakly influenced nitrate levels. Conclusions. In SLE, serum and urinary nitrate levels do not parallel lupus activity. Other variables, related or not to SLE, seem to aVect these levels. Nitric oxide (NO) is a biological messenger that when indicated by their clinical condition. At each visit, clinical evaluation was peformed. Special attenregulates physiological functions and participates in pathological processes. NO is synthesized from l- tion was paid to disease activity, selected organ involvement, presence of infection, and therapy. The SLE arginine, by constitutive NO synthases (cNOS) and inducible NO synthases (iNOS ), and is readily trans- Disease Activity Index (SLEDAI ) [15] was administered by the same investigator (MRG-C ) to all formed into nitrite and nitrate which are excreted into the urine. cNOS produce small amounts of NO which patients. When indicated, additional laboratory and radiological tests were carried out. The number of regulate blood vessel tone, platelet aggregation and neurotransmission. iNOS are stimulated by endotoxins accumulated ARA criteria, delay from diagnosis to study, tobacco use, history of hypertension and previ

We describe symptomatic hydrocephalus and secondary syndrome of inappropriate antidiuretic hormone as clinical manifestations of vertical atlantoaxial subluxation in a patient with severe rheumatoid arthritis. We found no reports of this association as a complication of rheumatoid cervical involvement. We discuss the difficulties of differential diagnosis and treatment in this patient.

In this paper we report a 47 year old woman with septic arthritis due to Streptococcus pneumoniae. No known predisposing factor was found. After an extensive workup a multiple myeloma was discovered. In our case septic arthritis was the first manifestation of multiple myeloma.

Purpose: EULAR guidelines for the treatment of Knee osteoarthritis (KOA) state that optimal management requires a combination of nonpharmacological and pharmacological modalities and that paracetamol is to be tried first. Our aim was to evaluate the predictive factors of the first choice line therapeutic strategy in general practitioners (GP)’ practice in France and Spain. Methods: Observational, prospective, multicenter 1-yr cohort study including patients 50 yrs, suffering from ACR defined KOA, not treated within the previous 6 months except for non-pharmacological treatment and/or self-medication with analgesics or low-dose NSAIDs and for whom it was planned to initiate a first line treatment according to the clinical status of the patient and the EULAR recommendations. Statistics. To identify the main predictive factors, multivariate analyses (logistic regressions) were performed with 1st choice modalities as dependent variables and clinical data at baseline as explanatory measures. Results: 383 GPs (50% in each country) included 1038 patients (69% females; means±SD: age 68±10 yrs, BMI 28.9±4.8 kg/m2, KOA duration 5.2±6.1 yrs). Since baseline patients’ characteristics in France and Spain were similar, both populations were pooled. Paracetamol alone was prescribed in 828 patients (440 with/388 without non-pharmacological modalities, mainly diet and/or exercices) and paracetamol plus other drugs (NSAIDs, SYSADOAs) were prescribed in 210 patients (114 with/96 without non pharmacological modalities). 1. Predictive factors of the association paracetamol + other drugs versus paracetamol alone are presented in table 1. Global GPs’ assessment, pain at night and effusion were significant factors in univariate (p< 0.05), but not in the multivariate analyses, while sex, age, BMI, past or present comorbidities, uni/bilateral KOA, recent flare-up of the pain, patient’s pain and patient’s global assessment were not significant at all. 2. The predictive factors of the association paracetamol + nonpharmacological treatments versus paracetamol alone are presented in table 2. Sex (females), bilateral KOA, self-medication, sick leave were significant in univariate, but not in the multivariate analyses. Conclusions: The predictive factors leading to the associations of nonpharmacological or other pharmacological modalities to paracetamol in the first GPs’ prescription for treating KOA seem different. Previous pharmacological treatment and request for specialist advice are good predictors of ajunction of other pharmaceuticals to paracetamol, while previous non-pharmacological treatments, obesity, recent flare-up and pain at night are predictors for the adjunction of non-pharmacological modalities.