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Objectives:To develop an ultrasound enthesis score and to assess its validity in the diagnostic classification of the spondyloarthropathies (SpAs).Methods:Twenty-five patients with SpA and 29 healthy controls participated in a blinded, gender-matched, cross-sectional study involving ultrasound assessment. The following entheses were explored bilaterally: proximal plantar fascia, distal Achilles tendon, distal and proximal patellar ligament, distal quadriceps and brachial triceps tendons. The ultrasound score evaluated enthesis thickness, structure, calcifications, erosions, bursae and power Doppler signal. The value of each elemental lesion was calculated using a three-model analysis. Validity was analysed by receiver operating characteristic (ROC) curves. Inter-reader and interexplorer intraclass correlation coefficients (ICCs) were calculated.Results:The logistic regression model overestimated the score of three elemental lesions: calcification (0–3), Doppler (0 or 3) and erosion (0 or 3), while scoring tendon structure, tendon thickness and bursa as 0 or 1. ROC curves established an ultrasound score of ⩾18 as the best cut-off point for differentiation between cases and controls. This cut-off point was exceeded by 5/29 controls (17%) and by 21/25 patients with SpA (84%). The sensitivity, specificity, positive and negative likelihood ratios (LR+, LR−) were 83.3%, 82.8%, 4.8% and 0.2%, respectively. The inter-reader and interexplorer ICCs were 0.60 and 0.86, respectively.Conclusion:The findings suggest that the ultrasound enthesis score could be a valid tool in the diagnosis of SpA.

Objectives:To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.Methods:751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. 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 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.Conclusions:Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

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.

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n  = 45) and risedronate (35 mg/week, n  = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

In patients with rheumatoid arthritis (RA), the development of antibodies to infliximab (ATI) is associated with poor clinical response. 1 2-7 Nevertheless, there is no plausible explanation for why not all patients with ATI experience high disease activity. Table 1 Total: 11 patients with RA (%) Gender, female n (%) 11 (100) Age, mean (SD) 54.18±13.24 Autoantibodies: RF positive n (%) 9 (81.8) ACPA positive n (%) 9 (81.8) Disease duration (years), mean (SD) 14.20±6.42 Baseline DAS28, mean (SD) 5.45±1.13 Time under Ifx therapy in years, mean (SD) 8.00±2.75 ATI duration in years, mean (SD) 1.1±0.91 Concomitant treatment MTX alone 3 (27.2) OD 1 (9.0) MTX+OD 6 (54.8) Ifx monotherapy 1 (9.0) ACPA, Anticitrullinated protein antibody; ATI, antibodies to infliximab; DAS28, Disease Activity Score 28; Ifx, infliximab; MTX, Methotrexate; OD, Other DMARDs; RF, Rheumatoid Factor.

Aims To evaluate the efficacy of methotrexate (MTX) in preventing the recurrence of acute anterior uveitis (AAU). Methods This prospective, open, longitudinal study included patients from June 2002 to March 2005 who had either three or more episodes of AAU in the previous year, or a recurrence of AAU within 3 months before starting the trial. We excluded uveitis of infectious origin, masquerade syndromes, and patients with contraindications to MTX. The response criteria were defined as an absence of symptoms and the presence of a normal ophthalmologic examination. The study outcome compared the number of flare-ups of uveitis over an MTX-treated for 1 year to the number of flare-ups of the same group during the previous year without MTX. Results A total of 571 patients with uveitis were evaluated during the period of the study, and 10 fulfilled the inclusion criteria. One patient refused the treatment, and nine completed the study. The mean number of recurrences in the pre-MTX year was 3.4 (SD: 0.52), which was significantly reduced to 0.89 (SD: 1.17) in the year of treatment ( P =0.011). Conclusion MTX treatment seems to reduce the number of flare-ups in patients with recurrent AAU.

Background:The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional B cells (cTrB) have been described in patients with longstanding RA.Objectives:To examine the frequency and evolution of cTrB cells in the peripheral blood of early RA (ERA) patients.Methods:Freshly isolated PBMCs from 48 steroid and DMARD-naïve ERA patients with a disease duration below 24 weeks and 48 healthy controls (HC) were examined by flow cytometry. Cocultures of isolated memory B cells were established with autologous T cells, in the absence or presence of TrB cells.Results:As compared with HC, ERA patients demonstrated an increased frequency of cTrB cells. cTrBs of ERA and HC displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFNγ and IL-21 production, together with ACPA secretion in autologous B/T cell cocultures. Basal frequencies of cTrBs above the median value observed in HC were associated with a good EULAR response to MTX at 12 months (RR=2.91; 95% CI, 1.37-6.47). A significant reduction of cTrBs was observed 12 months after initiating MTX, when the cTrB cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone.Conclusion:An increased frequency of regulatory cTrB cells is apparent in untreated ERA, and the baseline cTrB cell frequency is associated with the clinical response to MTX at 12 months.References:[1]Matsushita T, et al. J Clin Invest. 2008;118:342. Flores-Borja F, et al. Sci Transl Med. 2013;5:173ra23.Disclosure of Interests:Paula Fortea-Gordo Grant/research support from: BMS, Alejandro Villalba: None declared, Laura Nuño: None declared, Maria-Jose Santos-Bornez Grant/research support from: BMS, Diana Peiteado: None declared, Irene Monjo: None declared, Amaya Puig-Kröger: None declared, Paloma Sanchez-Mateos: None declared, Emilio Martín-Mola Grant/research support from: BMS, Roche, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Roche

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

Background Denosumab is the first biological treatment for osteoporosis in postmenopausal women at high risk of fracture or who have failed, or are intolerant to other osteoporosis treatment. Objectives To compare the effect of the treatment with denosumab to alendronate in postmenopausal women with osteoporosis and at high risk of fractures with regard to the variation of bone mineral density (BMD) and the incidence of new fractures. Methods This is a longitudinal and prospective study conducted at an outpatient rheumatology division of La Paz University Hospital, Madrid, Spain. Between 126 postmenopausal women ≥65 of age, with severe osteoporosis and history of fractures in most of them, who received 70mg alendronato (ALN) every week for more than two years, 75 patients suspended ALN for different reasons and they signed an informed consent to continue treatment with 60mg denosumab subcutaneously every 6 months. The other patients (n=51) decided to continue with 70 mg ALN every week. All patients received supplements of calcium and vitamin D, according to the individual levels. End points included percentage change from the beginning of the study in lumbar spine (LS) and femoral neck (FN) BMD at month 12 and new fractures incidence by dorsolumbar x-ray and clinic history. Results Denosumab-treated women and ALN-treated women were similar age: 73.8±7.1 and 71.7±6.0 years old, respectively. At month 12, significantly greater BMD increase from baseline were observed with denosumab compared with alendronate at LS (6.2±5.7% compared with 3.5±1.6%; p<0.001) and FN (4.3±4.9% compared with 1.9±1.5%; p=0.028). Reasons for ALN suspension were: 41.3% by lack of effectiveness in BMD increasing, 28% by intolerance gastroesophageal, 18.7% for new vertebral fractures, and 12% by decision of the patient. At basal time 62.7% of denosumab-treated women had suffered one or more osteoporotic fractures, after one year were not detected new fractures, all them received 2 doses of denosumab. At baseline, 58.8% ALN-treated women had fractures and after one year one vertebral and two Colles fractures were occurred and 87% of them completed treatment. Poor tolerance to subcutaneous injection or adverse events in any of the two treatment groups were not observed. Denosumab treated women expressed pleasure facility involving the semiannual administration of treatment. Conclusions In postmenopausal women with severe osteoporosis previously treated with alendronate, denosumab treatment resulted in greater BMD increases in lumbar spine and femoral neck than alendronate, probably associated with the better adherence due to the highest degree of satisfaction of the patients manifest to receive a six-monthly injection treatment. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2881

Objectives:To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA).Methods:The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale.Results:Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint.Conclusion:Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.