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Summary Background Temporal artery biopsy is considered the diagnostic gold standard for giant cell arteritis, despite approximately 39% of patients who are negative for the condition by biopsy subsequently being given a clinical diagnosis of giant cell arteritis. We aimed to assess the diagnostic accuracy of ultrasound examination in patients with suspected giant cell arteritis. Methods In this prospective, multicentre, non-interventional, cohort study (evaluation of ultrasound's role in patients suspected of having extracranial and cranial giant cell arteritis; EUREKA), we consecutively recruited patients aged 50 years or older, with clinically suspected giant cell arteritis from three Danish hospitals (South West Jutland Hospital in Esbjerg, Silkeborg Regional Hospital, and Rigshospitalet, Glostrup). Participants had a bilateral ultrasound of the temporal, facial, common carotid, and axillary arteries. Ultrasounds were done by ultrasonographers who were systematically trained in vascular ultrasound using appropriate equipment and settings. Participants then had a temporal artery biopsy within 7 days of initiation of corticosteroid treatment. A blinded ultrasound expert assessed all ultrasound images. Ultrasound vasculitis was defined in cranial arteries as a homogeneous, hypoechoic, intimamedia complex thickness and a positive compression sign and as a homogeneous intimamedia complex of 1 mm in thickness or wider in the axillary arteries and of 1·5 mm thickness or wider in the common carotid artery. Participants were followed up at 6 months. During this 6 month period, clinicians were able to collect data from all clinical examinations to enable a full clinical diagnosis at 6 months. Clinical diagnosis was based on the expert opinion of the treating rheumatologist. The diagnostic criterion standard was diagnosis confirmed after 6 months of follow-up. We used logistic regression analyses to calculate the odds ratio and 95% CI of ultrasound as a predictor for giant cell arteritis. Findings Between April 1, 2014, and July 31, 2017, 118 patients were screened for inclusion, of whom 106 had both ultrasound examinations and an eligible temporal artery biopsy and were included in the intention-to-diagnose population. The mean age was 72·7 years (SD 7·9), 63 (59%) participants were women, and 43 (41%) were men. Temporal artery biopsy was positive in 46 (43%) of 106 patients, and 62 (58%) of 106 patients had a clinically confirmed diagnosis of giant cell arteritis at 6 months (temporal artery biopsy sensitivity 74% [95% CI 62–84], specificity 100% [95% CI 92–100]). Cranial artery ultrasound was positive in all patients who had a positive temporal artery biopsy, and seven (58%) of 12 patients who were positive by ultrasound and negative by temporal artery biopsy were confirmed to have large-vessel giant cell arteritis via other imaging methods. The sensitivity of ultrasound diagnosis of giant cell arteritis was 94% (84–98) and specificity was 84% (70–93). Logistic regression analysis confirmed that ultrasound was the strongest baseline predictor for a clinically confirmed diagnosis of giant cell arteritis at 6 months (crude odds ratio 76·6 [95% CI 21·0–280·0]; adjusted for sex and age 141·0 [27·0–743·0]). Interpretation Vascular ultrasound might effectively replace temporal artery biopsy as a first-line diagnostic method in patients suspected of having giant cell arteritis when done by systematically trained ultrasonographers using appropriate equipment and settings. Funding The Institute for Regional Research at Hospital of Southwest Jutland, Esbjerg, Denmark.

Objective To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA. Methods Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria. Results When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with ‘no pain’ patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman’s rho = 0.11–0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01–0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23–0.66), US-modified CASPAR (0.17–0.57), and US-only (0.20–0.57) criteria. Conclusion Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.

ObjectiveSuccessful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).MethodsObservational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients.ResultsOf 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero.ConclusionThis real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

GCA is the most common large vessel vasculitis in the elderly population. In recent years, advanced imaging has changed the way GCA can be diagnosed in many locations. The GCA fast-track clinic approach combined with US examination allows prompt treatment and diagnosis with high certainty. Fast-track clinics have been shown to improve prognosis while being cost effective. However, all diagnostic modalities are highly operator dependent, and in many locations expertise in advanced imaging may not be available. In this paper, we review the current evidence on GCA diagnostics and propose a simple algorithm for diagnosing GCA for use by rheumatologists not working in specialist centres.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

Background: Temporal artery biopsy (TAB) is considered the diagnostic gold standard for giant cell arteritis (GCA), despite up to 39% of biopsy-negative patients receiving a clinical diagnosis of GCA. This is a prospective, multicentre study assessing the diagnostic utility of ultrasound examination in patients with suspected GCA. Methods: Participants were recruited from three Danish centres among patients with clinically suspected GCA. Temporal (TA), facial (FA), common carotid (CC), and axillary arteries (AA) were examined by ultrasonographers, systematically trained in vascular ultrasound, using appropriate equipment and settings, before TAB. A blinded ultrasound expert evaluated all images. The primary outcome was the proportion of participants with clinically diagnosed GCA confirmed after 6-month follow-up. Ultrasound vasculitis was defined in cranial arteries as increased, hypoechoic intima-media thickness (IMT) and a positive compression sign, in large vessels as homogeneous IMT ≥ 1 mm in the AA and ≥1·5 mm in the CA. Findings: One hundred six patients were included in the intention-to-survey population. TAB was positive in 46 patients (43%), and 64 (60%) patients had a clinically confirmed diagnosis of GCA at 6-month follow-up (TAB sensitivity 74%, 95% CI 62–84%, specificity 100%, 95% CI 92–100%). Cranial artery ultrasound was positive in all TAB-positive patients. The sensitivity and specificity of the ultrasound diagnosis of clinical GCA were 94% (84–98%) and 84% (70–93%). Logistic regression analysis confirmed that ultrasound was the strongest baseline predictor for a clinically confirmed diagnosis of GCA at 6 months (crude: OR 76·6, 21·0–280·0; Adjusted for sex and age OR=141·0, 27·0–743). Interpretation: Vascular ultrasound can effectively replace TAB as a first-line diagnostic modality in patients suspected of having GCA when applied by systematically trained ultrasonographers using appropriate equipment and settings. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Written consent was obtained from all participating patients according to the Declaration of Helsinki. The study was approved by The Regional Committees on Health Research Ethics for Southern Denmark (reference number S-2014003) and the Danish Data Protection Agency (reference number 2008-58-0035).

ObjectiveTo evaluate the impact of a standardised training programme including equipment adjustment for experienced musculoskeletal ultrasonographers without previous experience in vascular ultrasound (US) on the reliability of US in the diagnosis of giant cell arteritis (GCA).MethodsIn this prospective, non-interventional observational cohort study, patients suspected of GCA were evaluated by US by one of five rheumatologists with long-standing experience in musculoskeletal US (>8 years), trained using a standardised training programme including equipment adjustment. Images of cranial and large vessels were subsequently evaluated first by the performing ultrasonographer and thereafter by a blinded external expert (gold standard).ResultsIn three Danish centres, 112 patients suspected of GCA were included. According to the external expert, vasculitis changes were seen in 66 patients, in 45 of them with only cranial involvement, in 14 with both cranial and large vessel involvement, while in seven patients isolated large vessel vasculitis was found. The reliability was excellent between the local ultrasonographer and the US expert for the overall GCA diagnosis regarding the diagnosis of cranial and for large vessel GCA, with an interobserver agreement of 95–96%, mean kappa values of 0.88–0.92 (95% CI 0.78 to 0.99). Excellent reliability (mean kappa 0.86–1.00) was also found for the US examination of the individual arteries (temporal, facial, common carotid and axillary).ConclusionThe US training programme resulted in excellent agreement between trainees and an expert in patients suspected of GCA and may thus be applicable for implementation of vascular US in clinical practice.

Recent international guidelines recommend the use of biosimilar biological drugs on similar terms as their corresponding originators, including switching from a bio-originator to the biosimilar.1 However, the comparative safety of biosimilars in patients with inflammatory joint diseases (IJD) in routine care is still debated.2 In a phase 3 randomised trial among patients with rheumatoid arthritis, biosimilar etanercept (SB4) had slightly more hepatobiliary adverse events compared with the originator (ETN), possibly explained by differences in patients’ comorbid diseases and comedication use.3 The occurrence of, for example, hepatobiliary safety events is likely to differ across indications (due to differences in age, body weight, use of methotrexate, comedication, etc) and has not been explored in etanercept-treated patients with psoriatic arthritis or axial spondyloarthritis.4 In April 2016, a mandatory switch from ETN to SB4 was performed in Denmark to save costs and the 1-year clinical …

Thank you for the interest1 in our recent publication, in which we explored treatment outcomes following a Danish mandatory switch from originator to biosimilar etanercept (SB4, 50 mg) in routine care.2 We showed that of the 2061 patients who were receiving originator etanercept and thus were eligible for the switch, as many as four of five (79%) switched to the biosimilar, despite the continued availability of the originator drug (as 25 mg pen or 50 mg powder solution). Among the patients who switched, we observed high retention rates of the biosimilar. The 6-month …

Objective.To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.Methods.A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min.Results.In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments.Conclusion.OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

ObjectivesAccording to guidelines, a nationwide non-medical switch from originator (INX, Remicade) to biosimilar infliximab (Remsima, CT-P13) was conducted in Danish patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). We investigated disease activity before/after switching and retention rates in the DANBIO registry.MethodsDisease activities 3 months before and after switch and changes over time were calculated. Flare was defined as change in 28 Joint Disease Activity Score (∆DAS28) ≥1.2 (RA/PsA) or Ankylosing Spondylitis Disease Activity Score (∆ASDAS) ≥1.3 (AxSpA). Crude and adjusted retention rates were compared with a historic cohort of INX-treated patients.ResultsEight hundred and two patients switched (403 RA/120 PsA/279 AxSpA; 51% women, age (median (IQR): 55 (44-66)) years). Follow-up was 413 (339–442) days. Prior INX treatment duration was 6.8 (4.3–9.5) years. Disease activities were similar 3 months before/after switch. Crude 1-year CT-P13 retention rate (84.1 (95% CI 81.3 to 86.5)) was similar to the historic IFX cohort (86.2 (95% CI 84.0 to 88.0), p=0.22). The adjusted absolute retention rates were 83.4 (95% CI 80.8 to 86.2) and 86.8% (95% CI 84.8 to 88.8), respectively (p=0.03). In total 132 patients withdrew (lack of effect: 71/132=54%, adverse events: 37/132=28%). Patients with previous INX treatment duration >5 years had longer CT-P13 retention.ConclusionIn 802 arthritis patients treated with INX for median >6 years, a nationwide non-medical switch to CT-P13 had no negative impact on disease activity. Adjusted 1-year CT-P13 retention rate was slightly lower than for INX in a historic cohort.

ObjectiveTo develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren’s syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips.MethodsTwenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren’s syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1–5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions.ResultsConsensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen’s kappa 0.81) and inter-reader reliability was good (Light’s kappa 0.66).ConclusionNew definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.

Background Polymyalgia Rheumatica (PMR) is a common inflammatory autoimmune rheumatic disease, with the highest incidence rates seen in Scandinavia. One of the challenges in the diagnosis of PMR is the lack of diagnostic tests specific for the disease. The diagnosis may require exclusion of other conditions that can present with polymyalgia symptoms and may lead to hospitalization. Only limited data on hospitalization rates among patients with PMR exists (1). Ultrasound (US) may be useful in differentiating PMR from non-inflammatory conditions and can also be used for the diagnosis of concomitant Giant Cell Arteritis (GCA) GCA Fast Track Clinics (FT) using US as the main diagnostic tool have shown both improvement in patient outcomes and decrease in the cost of care(2) Objectives To investigate the admission rates of patients diagnosed with PMR and the impact of the FT on these rates. Methods A FT clinic for patients suspected to have PMR was established at rheumatological outpatient clinic of South-West Jutland Hospital (serving 250.000inhabitants) in January 2018. Collaboration with the Emergency Medical department was established and patients with PMR symptoms referred to the hospital were examined at FT within 0-1 days, thereby avoiding hospitalization. Similarly, patients referred with PMR symptoms to the outpatient clinic by a GP, were examined at FT within 1-2 days. At FT a thorough history and clinical examination were performed including musculoskeletal and vascular US. Retrospectively data from patients diagnosed with PMR from 2013-2018 was analyzed. Results In a 6 years’ period, 336 patients were diagnosed with PMR. 54 patients were diagnosed during hospitalization. Hospitalized patients were older (mean values ± standart deviaton-sd) 73,61±8,96 vs 70,94±7,97 years, p=0,024, with significantly higher initial C-reactive protein(CRP, mg/l) levels 99±58,8 vs 43,9±37,p Conclusion The annual hospitalization rates in connection with PMR diagnosis at South-west Denmark during a 5 year period were estimated to be 19,2%. The implementation of a FT ultrasound clinic decreased significantly the hospitalization rates among patients with PMR. References [1] Gran JT,Myklebust G. The incidence of PMR and temporal arteritis in the county of Aust Agder, South Norway: a prospective study 1987–94. J Rheumatol1997. [2] Diamantopoulos APet.al. The fast-track ultrasound clinic for early diagnosis of GCA significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical outcome in giant cell arteritis?Rheumatology (Oxford)55:66–70 Disclosure of Interests None declared

Background Interstitial lung disease (ILD) evaluation is challenging, given the low sensitivity of X-ray and pulmonary function tests, and limited accessibility and radiation linked to repetitive HRCT. Lung Ultrasound (US) has shown potential in the evaluation of ILD of autoimmune diseases including systemic sclerosis. Objectives To define and asses the reliability of definitions of US-detected findings in ILD. Methods A taskforce (TF) within the OMERACT US WG performed a literature review (LR) to identify US lesions in ILD, a Delphi exercise to define these lesions and a web-based exercise to test the reliability of these definitions by using either intraclass correlation coefficient (ICC) or kappa statistics. Prior to the Delphi exercise all participants received training files and were subsequently asked to provide clips on BL, PLI and normal findings. Based on the results of the LR, which identified B-lines (BL) and pleural line irregularity (PLI) as main US findings in ILD, the Delphi exercise contained statements on US definitions on BL and PLI. After reaching agreement (> 75%) on the above mentioned items, a set of 80 high-quality clips (30 for PLI, 50 for BL), was selected and distributed to the TF members in order to score them (semiquantitatively, 0-2 for PLI and total number for BL) Results The 3 Delphi rounds and the web-based exercise were completed by 24 and 22 sonographers, respectively. Final definitions are reported in Table I. The web-based exercise showed moderate inter-reader reliability for both BL (ICC=0.61) and PLI (kappa=0.69). Table I: definitions of PLI and BL Pleural line irregularity (PLI): a loss of regularity that may be associated with an increase in thickness, focal, diffuse, or nodular B-line (BL): a vertical hyperechoic reverberation artifacts that arise from the pleural line, extend to the bottom of the screen without fading, and move synchronously with lung sliding Conclusion US is a candidate imaging modality to identify and monitor ILD in rheumatic diseases; US consensus based definitions of main US findings were defined and endorsed. Further development is planned for validating US as an outcome measurement instrument for ILD. Disclosure of Interests Andrea Delle Sedie Speakers bureau: Abbvie, UCB, Celgene, MSD, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene, George Bruyn : None declared, Tomas Cazenave: None declared, stavros chrysidis: None declared, Mario Diaz: None declared, Marco Di Carlo: None declared, Marilena Frigato: None declared, Luna Gargani: None declared, Marwin Gutierrez: None declared, ALOJZIJA HOCEVAR: None declared, Annamaria Iagnocco: None declared, Aaron Juche: None declared, Peter Mandl: None declared, Esperanza Naredo Consultant for: Abbvie, Speakers bureau: AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen, and Celgene GmbH, Mohammed A Mortada: None declared, Carlos Pineda: None declared, Francesco Porta: None declared, Viviana Ravagnani: None declared, Carlo Alberto Scire: None declared, Teodora Serban: None declared, Kate Smith: None declared, Maria Stoenoiu Grant/research support from: Abbvie, Roche, Wyeth, Marika Tardella: None declared, Karina Torralba: None declared, Richard Wakefield: None declared, Maria-Antonietta d’Agostino: None declared

ObjectivesReal-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised.MethodsObservational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted).Results1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months’ preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers’ clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective.ConclusionSeventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Objectives In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA). Methods Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months’ remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication). Results Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months’ remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched. Conclusion This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

Background:Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease of people over 50 years in Scandinavian countries and people of northern European descent, characterized by proximal pain, stiffness, raised inflammatory markers and prompt response to steroids(1). Relapse free during tapering off prednisone, are common in approximately 50% of patients. Studies reported that up to 70% of PMR patients are successfully tapered of prednisone due to remission, within 1-2 years from treatment initiation (1). Telemedicine has found a wider application in a number of chronic diseases resulting in a decreased number of hospital visits; however, no telemedicine studies on PMR patients have been performed before (2).Objectives:To evaluate the use of telemedicine consultation in newly diagnosed PMR patients.Methods:Telemedicine consultations managed by rheumatic nurses for newly diagnosed PMR patients was established in 2017 at our department. Patients diagnosed with PMR by a rheumatologist received written information concerning the nature of the disease, a “follow-up” schedule and a prednisone treatment/tapering plan. Telephone consultations (TC) including relevant blood analysis was planned after 4, 16, 52 and 78 weeks from the time of diagnosis. TC was managed by 4 nurses specialized in rheumatic diseases, who received appropriate education of PMR prior to the establishment. A predefined questionnaire was used for every telephone consultation.All PMR patients were initially treated with 15 mg of prednisone daily, with slowly tapering to 5 mg daily at week 16 and reduced to zero at week 48. In the case of relapse symptoms, patients were instructed to contact the treating nurses. In that case, relevant biomarkers were taken and a rheumatologist evaluated the need for a physical consultation and potential treatment adjustment.Only patients with minimum disease duration of 3 months were included in the study.Results:In a period of two years, 76 patients were evaluated. The mean age was 73 years and the mean follow up period was 10, 67 ± standard deviation (SD) 5,2 months. At the time of diagnosis, all patients fulfilled the 2012 Classifications criteria for PMR (3). The Mean number of TC was 4.27(± SD 2, 3).In 45 cases (60%) no additional physical consultation was necessary. In patients examined physically due to relapse suspicion, the most common findings were PMR relapses (66%), followed by non-inflammatory muscle and joint pain (18,5%), arthritis (14%), while one patient was diagnosed with giant cell arteritis.Successfully prednisone tapering was achieved in 23 cases (30%) while 27 patients (35,5%) at the time of data evaluation were treated with only 2,5 mg of prednisone daily. The mean current daily prednisolone dosage was 3.95 mg (± SD 3.25) while disease-modifying-anti-rheumatic-drugs had been initiated in 6 patients.Conclusion:Telemedicine consultations in PMR diminish the need for physical consultations in this patient cohort. More than half of all patients were either out of- or received only a very low dose of prednisone at the time of evaluation of data.References:[1]Kermani TA, Warrington KJ. Polymyalgia rheumatica. Lancet. 2013 Jan 5;381(9860):63-72. doi: 10.1016/S0140-6736(12)60680-1.[2]Matteo Piga et al. Telemedicine for patients with rheumatic diseases: Systematic review and proposal for research agenda. Semin Arthritis Rheum. 2017 Aug;47(1):121-128. doi: 10.1016/j.semarthrit.2017.03.014. Epub 2017 Mar 22.[3]Dasgupta B, et al. 2012 Provisional classification criteria for polymyalgia rheumatica: A European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum. 2012; 64: 943-54.Disclosure of Interests:None declared

Background:Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease at persons > 50 years of age. It is clinically characterized by pain and stiffness in the neck, proximal shoulder, and hip girdle. (1)Glucocorticoid (GC) is the cornerstone of PMR treatment; the use is associated with potentially severe side effects (3).According to EULAR-ACR recommendations for the management of PMR, treatment should be individualized using the minimum effective GC dose. (2)An initial prednisolone dose of > 15mg is associated with significantly higher risk for GCs related side effects (1) and GC doses higher than 25 mg/day are discouraged because of the high risk of adverse events; furthermore, there is no evidence that such doses are more effective than lower doses (2,3).In most countries, the vast majority of PMR patients are diagnosed and managed primarily by their General Practitioner (GP) (4)Objectives:To compare the initial GC dose for PMR patients diagnosed by their GP versus an outpatient rheumatological clinic in Denmark.Methods:All patients with the diagnosis of PMR in South-West Jutland Hospital, Denmark at the period of 2013 to 2018 were identified from an electronic register.Patients with an already known rheumatic disease before the diagnosis of PMR, GCA symptoms at the diagnosis time or hospitalized at the diagnostic time were excluded.Clinical and paraclinical data were collected from the patient’s electronic journal.Results:In a period of 6 years, 342 patients with PMR were identified. Of 342 patients 83 were diagnosed by their GP. No significant differences were found regarding demographical, clinical and paraclinical baseline characteristics between the two groups. No differences were identified regarding the treatment response. However the initial prednisone dose in patients diagnosed by the GP’s was significantly higher (pTable 1.Diagnosed by GPsN 83Diagnosed by the rheumatological outpatient clinicN 259P valuesAge (years) ± SD70,2 ± 8,270,58± 7,5n.s*Gender-female(%)62,6%56,7%n.s*Duration of symptoms (weeks)± SD12,34 ± 1012,9 ± 13,4n.s*Age over 50 %98,8%99,6%n.sBilateral shoulder pain (%)95,1%96,5%n.sAbnormal CP and/or SR (%)87,8%94,2%n.s*CRP (mg/lt) ± SD36,8 ± 32,245,8± 36,8n.s*SR(mm/hour) ± SD50,1±26,555,1±23,7n.s*Morning stiffness87,9%91%n.s*Hip pain or limited range of motion66,2%70,4%n.s*RF and aCCP negative %87,9%90,2%n.s*Absence of other joint involvement79,5%71%n.s*Initial prednisolone dose(mg) ± SD25,65 ± 12,116,4±4,5Response to treatment93,9%94,1%n.s*non-significantConclusion:Our study shows that the initial GC dose is significantly higher for PMR patients diagnosed by GPs which may lead to a higher risk of GC related side effects.References:[1]Camellino D, Dejaco C. Update on treatment of polymyalgia rheumatica Reumatismo. 2018 Mar 27;70(1):59-66. doi: 10.4081/reumatismo.2018.1062.[2]Dejaco C, Singh YP, Perel P, et al. 2015 recommendations for the management of polymyalgia rheumatica: A European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2015; 74: 1799-807[3]Dejaco C, Singh YP, Perel P, et al. Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/ American College of Rheumatology recommendations for the management of po. Ann Rheum Dis. 2015; 74: 1808-17.[4]Helliwell T, Muller S, Hider SL, Zwierska I, Lawton S, Richardson J, Mallen C. Challenges of diagnosing and managing polymyalgia rheumatica: a multi methods study in UK general practice. Br J Gen Pract. 2018 Nov;68(676):e783-e793. doi: 10.3399/bjgp18X699557.Disclosure of Interests:None declared

Background:Giant Cell Arteritis (GCA) is one of the most common systemic vasculitis. Temporal artery biopsy (TAB) has been the standard test to confirm the diagnosis of GCA. However, TAB has a lower sensitivity than clinical diagnosis and up to 44% of biopsy-negative patients are clinically diagnosed as having GCA.In a recent meta-analysis of the diagnostic performance of ultrasound (US) in GCA the sensitivity was 77 % (1). The included studies were performed by expert groups in single centres. In the to date only multicentre study (TABUL) investigating the diagnostic accuracy of US compared to clinical diagnosis after 6 months the sensitivity was lower (54%) (2)Objectives:To evaluate the diagnostic accuracy of vascular US compared to TAB in a multicentre study.Methods:In three Danish centres patients suspected for GCA were included during a period of two years. At baseline, clinical and laboratory data were collected and vascular US of temporal, facial, common carotid and axillary artery were performed. The US examinations were performed with high frequency transducers (15-18 MHZ) and followed by a TAB. All ultrasongraphers had participated in the same standardized US educational program and were blinded to clinical and laboratory data. An external expert blinded to clinical and laboratory data evaluated all images and made the final US diagnosis.A positive sign for vasculitis in cranial arteries was defined as a hypoechoic intima media complex (IMC) thickening (halo sign) and a positive compression sign. A homogeneous IMC increased thickness in axillary artery of ≥1mm and in common carotid artery ≥1.5mm was defined as vasculitis.The consultant rheumatologist’s diagnosis at 6 months after initial presentation was considered as the reference standard for the diagnosis of GCA.Results:During the recruitment period, 112 patients were included, 59% females, mean (SD) age 72.4(7.9) years, among which 91(81.3%) fulfilled the ACR 1990 classification criteria for GCA. 92% of the patients reported a newly emerged localized headache, while 49 (43.8%) experienced polymyalgia rheumatic symptoms.TAB was positive in 46(41.1%) and inconclusive in 6 patients, who were excluded from the analysis. Mean (SD) duration of glucocorticoid therapy prior to US and TAB was 0.91(1.55) and 4.02(2.61) days, respectively. In 62 patients, the final diagnosis was GCA.In all patients with a positive TAB, the US of the temporal artery was also positive for GCA. Of 19 cases with positive US and negative TAB, 12 were clinically diagnosed with GCA of whom 6 had isolated large vessel involvement on US. Among 41 patients with both negative US and TAB, 4 were clinically diagnosed with GCA (Box 1)US had a sensitivity of 93% and specificity of 84% for the diagnosis of GCA, while the sensitivity for TAB was lower (74%) with a specificity of 100%. For the diagnosis of GCA, US had a PPV of 89.2 % and a NPV of 90.2%, while for TAB the PPV was 100% and the NPV 73.3%.Conclusion:US evaluation of the temporal, facial and selected supraaortic arteries performed by trained ultrasonographers can replace biopsy in the diagnosis of GCA.Box.1References:[1]Duftner C, Dejaco C, et al. Imaging in diagnosis, outcome prediction and monitoring of large vessel vasculitis: a systematic literature review and metaanalysis informing the EULAR recommendations. RMD Open 2018;4:e000612.[2]Luqmani R et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. Health Technol Assess 2016;20:1_238.Disclosure of Interests:stavros chrysidis: None declared, Uffe Møller Døhn: None declared, Lene Terslev Speakers bureau: LT declares speakers fees from Roche, MSD, BMS, Pfizer, AbbVie, Novartis, and Janssen., Ulrich Fredberg: None declared, Tove Lorenzen: None declared, Robin Christensen: None declared, Per Søndergaard: None declared, Jakob Matthisson: None declared, Knud Larsen: None declared, Andreas Diamandopoulos: None declared

Background:Due to a high level of evidence of good test performance, accessibility, minimal invasiveness, low cost, and good overall performance, EULAR recommends ultrasound (US) of the temporal and axillary arteries as primary diagnostic imaging test in patients suspected of Giant Cell Arteritis (GCA) (1).Despite the growing body of evidence supporting the utility of US in GCA, standardized training programs and their impact on reliability are lacking(1). In TABUL study (2), the only US study published to date using a standardised US training program, the interobserver agreement by 12 different sonographers was only moderate, illustrating the challenges presented in the education for US in GCA.Objectives:To evaluate the impact of a standardized training program including equipment adjustment on the agreement and reliability of US in the diagnosis of GCA for experienced musculoskeletal (MSK)ultrasonographers, without previous experience on vascular US.Methods:Five rheumatologists with long-standing experience in MSK US were trained by a standardized training program including equipment adjustment (Box 1) prior to a prospective, non-interventional observational study in patients suspected having GCA.The rheumatologist performing the US subsequently evaluated the images blinded to the patients data. Thereafter the images were evaluated by a blinded external expert (i.e. considered the gold standard).Results:In three Danish centers 112 patients were included, 59% females, mean age 72.4 (SD) 7.9 years and median CRP 55 (IQR 21-100)mg/l. Median duration of prednisolone treatment prior to US examination was 0 (IQR 0 to 1) days. 92% of the patients reported a newly emerged localized headache.The reliability between the performing ultrasonographer and the US expert for the overall GCA diagnosis, as for the diagnosis of cranial (c-GCA) and large-vessel GCA (Lv-GCA) was excellent. In addition, excellent reliability was also found for the US examination of all examined arteries (Table 1). According to the US expert, vasculitis changes were found in 66 patients with the pathological findings distributed as presented in table 1.Table 1VariablesPathological findings (%)Interobserver agreement (%)Interobserver ReliabilityKappa Coefficient95% Confidence LimitsUS positive for GCA59%96%0.930.85-0.9966/112US positive for cGCA53%95%0.890.81-0.9859/112US positive for Lv-GCA19%96%0.890.78-0.99521/112Halo sign TA, all51%96%0.910.83-0.99segments57/112Compression sign TA,48%94%0.890.80-0.9851/107all segmentsHalo sign FA20%96%0.870.75-0.9823/112Compression sign16%96%0.860.73-0.99FA17/107Halo sign AA18%97%0.910.81-1.0020/112Halo sign AC4%100%1.001.00-1.006/11TA: Temporal; FA: Facial; AA: Axillary; AC: common Carotid, arteryConclusion:Our training program resulted in excellent reliability of US findings in patients suspected of having GCA and for the final diagnosis. The training program could be used when implementing vascular US in clinical practice.Box 1References:[1]Dejaco C et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018;77:636[2]Luqmani R et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis: a diagnostic accuracy and cost-effectiveness study Health Technol Assess 2016;20:1_238Disclosure of Interests:stavros chrysidis: None declared, Lene Terslev Speakers bureau: LT declares speakers fees from Roche, MSD, BMS, Pfizer, AbbVie, Novartis, and Janssen., Robin Christensen: None declared, Ulrich Fredberg: None declared, Knud Larsen: None declared, Tove Lorenzen: None declared, Uffe Møller Døhn: None declared, Andreas Diamandopoulos: None declared

Background In Denmark, patients (pts) treated with originator etanercept (ETA) 50 mg SC conducted a mandatory non-medical switch to biosimilar SB4 in April 2016 (switchers). Pts treated with 25 mg ETA or 50 mg powder-solution were not mandated to switch (non-switchers). Some switchers resumed ETA during follow-up (back-switchers). Objectives To investigate the frequency of back-switching after the non-medical switch from ETA to SB4, and in back-switchers to study, 1) baseline characteristics at the time of initial switch (ETA->SB4), 2) reasons for SB4 withdrawal, 3) changes in disease activity during treatment with SB4 and after back-switching. Methods Patient data were retrieved from the DANBIO registry (censored August 2017). For back-switchers, disease activity at the start of SB4 (=baseline) and at the time of back-switching to ETA were compared, and changes in disease activity between the two time points were calculated (=delta values), stratified by indication (RA/PsA/AxSpA). Baseline characteristics of back-switchers were compared to the rest of the switch population (Chi-sq, Mann-Whitney U-test). Abbreviations are shown in table 1. Results 1641 pts switched from ETA to SB4. Of these, 299 (18%) withdrew SB4 therapy during 1 year follow-up and either switched back to ETA (n=120, 7%), started another bDMARD (n=104), died (n=9), were lost to follow-up (n=1) or did not re-start bDMARDs (n=65). Among the 120 back-switchers, SB4 was withdrawn due to LOE (52%), AE (39%), or other/unknown reasons (9%). The reasons for withdrawal of SB4 in back-switchers are listed in table 1. No major safety events occurred. The median time on SB4 before back-switching was 120 (IQR 73–193) days, and the time between stop of SB4 and re-start of ETA was 11–1 days. Baseline characteristics of back-switchers vs the rest of the switch population were similar (all p>0.05). Among back-switchers who stopped SB4 due to LOE, PGA increased during SB4 treatment, whereas CRP and SJC were largely unchanged (table 1). At the date of censoring, 104/120 back-switchers (87%) were still treated with originator ETA (median treatment duration 236 (155–302) days). Conclusions In a nationwide cohort of 1621 arthritis patients that were switched from ETA to SB4, 7% switched back to ETA. Back-switchers had no distinct clinical or disease characteristics upon start of SB4. AEs prior to back-switching were largely unspecific. In pts who withdrew SB4 due to LOE, PGA had increased. Reasons for back-switching appeared to be predominantly subjective rather than objective (nocebo effect). Originator drug was still available (25 mg or 50 mg powder-solution), which may have encouraged back-switching. References [1] Glintborg, et al. Arthritis Rheum2017;69(suppl 10). [2] Glintborg, et al. Abstract, EULAR2018. Acknowledgements Partly sponsored by Biogen Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, Pfizer, I. Sorensen: None declared, E. Omerovic: None declared, F. Mehnert: None declared, N. Manilo: None declared, K. Danebod: None declared, D. Jensen: None declared, H. Nordin: None declared, A. G. Loft Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, O. Hendricks Grant/research support from: Abbvie, Roche, Novartis, S. Chrysidis: None declared, B. Andersen: None declared, J. Raun: None declared, H. Lindegaard: None declared, J. Espesen: None declared, S. Jakobsen: None declared, I. M. Hansen Grant/research support from: Roche, E. Dalsgaard: None declared, D. Pedersen: None declared, S. Kristensen: None declared, A. Linauskas: None declared, L. Andersen: None declared, J. Grydehoj: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB

Background In Denmark, rheumatoid arthritis(RA), psoriatic arthritis(PsA) and axial spondyloarthritis(AxSpA) patients (pts) treated with originator etanercept (ETA) 50 mg SC conducted a mandatory non-medical switch to biosimilar Etanercept (SB4) in April 2016 (switchers). Pts treated with 25 mg ETA or 50 mg powder solution were not mandated to switch (non-switchers). Objectives To characterise switchers and non-switchers, and to compare 1 year treatment retention in switchers with non-switchers and a historic cohort of ETA treated pts. Methods Pt data were retrieved from the DANBIO registry and national registries. We applied Chi-square/Mann-Whitney for comparisons and Kaplan-Meier/Cox regression analyses (crude, adjusted for gender/age/MTX/remission/comorbidities/ETA-start-year) for drug retention. The historic cohort encompassed pts treated with ETA by Jan 1st 2015. Results Of 2,061 ETA treated pts by April 2016, 79% switched to SB4 (933RA/351PsA/337AxSpA), whereas 21% (286RA/56PsA/98AxSpA) continued ETA. In RA, compared to switchers, non-switchers more often received 25 mg ETA, had higher disease activity and HAQ (table 1). Similar patterns were seen for PsA and AxSpA. Median(IQR) follow-up was 383(314–414)days. In all 3 cohorts, withdrawals were mainly due to lack of effect. Retention rate was lowest in non-switchers (figure 1). 1 year adjusted rates were 83% (95% CI 79–87) in switchers, 77%(72–82 in non-switchers and 90%(88–92 in historic cohort. Pts not in remission had poorer retention than pts in remission both in switchers (hazard ratio 1.7 (1.3–2.2) and non-switchers (2.4 (1.7–3.6)). Numbers are medians (IQR) unless otherwise stated. * DAS28 Conclusions Of >2000 ETA treated pts, ≈80% switched to SB4. Non-switchers had higher disease activity and more often received 25 mg ETA. Switchers had poorer retention rate than a historic ETA-cohort, but better than non-switchers. Withdrawal was most common in pts not in remission. These real-world data indicate that a switching-to-biosimilar option facilitated clinical decision making in standard care, leading to withdrawal from ineffective therapy in both switchers and non-switchers. Acknowledgements Partly sponsered by Biogen Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, Pfizer, I. Sorensen: None declared, E. Omerovic: None declared, F. Mehnert: None declared, N. Manilo: None declared, K. Danebod: None declared, D. Jensen: None declared, H. Nordin: None declared, A. G. Loft Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, O. Hendricks Grant/research support from:: Abbvie, Roche, Novartis, S. Chrysidis: None declared, B. Andersen: None declared, J. Raun: None declared, H. Lindegaard: None declared, J. Espesen: None declared, S. Jakobsen: None declared, I. M. Hansen Grant/research support from: Roche, E. Dalsgaard: None declared, D. Pedersen: None declared, S. Kristensen: None declared, A. Linauskas: None declared, L. Andersen: None declared, J. Grydehoj: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

INTRODUCTION: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis.METHODS AND ANALYSIS: All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients.ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences.

Background In Denmark, biological drugs are provided free by the hospitals to the patients via a tax-based system. In 2015 a non-medical switch from originator infliximab to CT-P13 was conducted (1). According to national guidelines in April 2016, a non-medical switch from originator (ETA, Enbrel® 50 mg/week) to biosimilar etanercept (SB4, Benepali®) was dictated when SB4 was marketed, including patients with inflammatory rheumatic diseases treated in routine care. Objectives To investigate 3 months9 disease activity and 5 months9 treatment withdrawal in ETA-treated patients (pts) with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthrits (SpA), who were switched to SB4 and monitored prospectively in the DANBIO registry. Methods Pts with RA/PsA/SpA followed in DANBIO since start of first bDMARD were included. Disease activity at 3 months before switch (pre-switch), at the switch and after 3 months (post-switch) and changes over time (Δpre-switch and Δpost-switch) were calculated. Disease flare was defined as ΔDAS28≥1.2 (RA/PsA) or ΔASDAS≥1.3 (SpA). Factors associated with withdrawal (gender/age/diagnosis/bDMARD-treatment-no/comedication methotrexate/baseline CRP/patient9s global score) were explored by multivariable Cox regression analysis. Results In total, 1548 switch pts were identified (891 RA, 335 PsA, 322 SpA). 60% were women, age (median (IQR) 56 (44–65) yrs)). Prior ETA treatment duration was 5.2 (3.2–8.0) yrs. ETA was the first biological treatment in 49%, and the second in 33% of pts. Concomitant MTX was given in 60% (RA)/49% (PsA)/15% (SpA). Median follow-up time was 154 (110–178) days. Disease activity remained largely unchanged 3 months prior to vs. after the switch (Table). The proportion of patients with disease flare pre-/post switch was 8%/13% (RA), 9%/13% (PsA), 5%/5% (SpA). Overall, 129 pts (9%) stopped SB4 treatment during 5 months9 follow-up (Table). Prior ETA treatment duration in these patients was 4.5 (2.7–7.1) years. Higher patient9s global score (HR 1.12/cm, 95% CI (1.05–1.21), p=0.002) and no concomitant methotrexate (HR 2.28 (1.48–3.52), p Conclusions In 1548 patients with inflammatory rheumatic diseases treated with ETA for >5 years, disease activity was largely unaffected in the majority of patients 3 months after non-medical switch to SB4 and comparable to the fluctuations observed in the 3 months prior to the switch. Several patients (≈9%) stopped treatment during 5 months follow-up. Higher patient9s global score and no use of methotrexate were associated with withdrawal. Longer follow-up will offer additional understanding of the potential efficacy and safety consequences of the non-medical switch. References Glintborg et al. Arthritis Rheumatol. 2016; 68 (suppl 10): Abstract no 951. Acknowledgements Data analysis was partly financially supported by Biogen. Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, I. Sorensen: None declared, A. G. Loft: None declared, J. Esbesen: None declared, H. Lindegaard: None declared, D. Jensen: None declared, K. Danebod: None declared, S. Dieperink: None declared, O. Hendricks: None declared, I. M. Hansen Grant/research support from: Roche, A. Linauskas: None declared, S. Kristensen: None declared, L. Andersen: None declared, M. Hossein: None declared, H. Nordin: None declared, B. Andersen: None declared, S. Chrysidis: None declared, J. Raun: None declared, N. Manilo: None declared, J. Grydehoj: None declared, E. Dalgaard: None declared, D. Pedersen: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Orion, BMS, AbbVie, Biogen, Pfizer, MSD, Eli Lilly

Background Ultrasonography (US) of salivary glands (USSG) may support diagnosis and evaluation of disease activity in primary Sjogren9s syndrome pSS. In order to extent the use of USSG in daily practice, consensus definitions of normal and abnormal USSG findings are needed. Objectives To obtain consensual definitions of normal and abnormal USSG findings using a Delphi process. Methods Twenty-seven experts participated in the Delphi process. A Likert scale from 1–5 was used in which 1 indicated complete disagreement and 5 complete agreement. Three core items were proposed: 1. Consensus of assessment of SG (parotid gland (PG), submandibular glands (SMG), sublingual glands SLG)). 2. Consensus for elementary lesions of PG, SMG, and SLG changes in PSS patients. 3. Consensus on grading of PG, SM, and SLG in pSS. Results The consensus of definitions between experts was reached after three rounds.The results (table 1) showed agreement with more than 75% of agreement in normal and abnormal definitions in SG and concluded to not evaluate SLG in pSS patients as well as to score pSS SG patients with at least two abnormal glands out of 4 (2 PG and 2 SMG) with a scoring system >2 for each abnormal gland. Conclusions We developed a consensual US definition of normal and abnormal USGS findings through a Delphi exercise process. This finding will be used as a basis to further proceed with the validation of USGS for clinical application. Disclosure of Interest None declared

To clarify if musculoskeletal ultrasound (MSUS) improves early diagnosis of RA when added to the clinical examination of patients with possible arthritis. We performed a systematic literature review of original studies dealing with the value of MSUS in the early diagnosis of RA. Studies were identified using the databases of PubMed, EMBASE and Cochrane library. Only studies in English investigating populations with non-classified arthritis or arthralgia were included. Fifteen original studies investigating the added value of MSUS in diagnosing RA were identified. They differed in sample size, study population, serology status, number of joints investigated and regarding the ultrasound machines and probes used. Thirteen out of 15 studies concluded that use of MSUS had an added value compared to clinical examination and laboratory evaluation alone for diagnosing RA. One study found that MSUS did not add substantial discriminatory value for predicting RA in an early arthritis cohort when added to routine assessment. However, in this study only 16 joints were examined (wrists and MTP 3-5 were not included). One study investigated only seropositive patients and found no significant advantage of MSUS on patient level although a trend was noted. Accordingly, two other studies found MSUS to be useful especially in seronegative patients. The use of MSUS adds value in diagnosing early RA, especially in seronegative arthritis. However, no study to date has documented any effect of DMARD initiation based on MSUS findings (subclinical arthritis) alone. More studies investigating this matter are warranted.

Thank you for the interest in our publication based on data from the Danish DANBIO registry regarding 2061 patients who were eligible for a mandatory non-medical switch from originator to biosimilar etanercept in routine care.1 2 The marketing of biosimilars has changed the landscape of the biological drugs with the potential for huge cost reductions, most markedly if patients may be switched from an ongoing successful treatment with the expensive originator to a much cheaper biosimilar. Thus, up to 75% price reduction has been experienced in Denmark so far with no evidence of increased use of health resources.3 The outcomes of a non-medical switch of etanercept in the real-world setting are, however, largely unknown, since prevous publications on switching in routine care have included limited numbers of patients. The aim of the study was therefore to investigate the effectiveness of a large-scale, …

OBJECTIVES: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses in patients with AS treated with their first tumour necrosis factor-alpha inhibitor (TNFi) therapy in routine care.METHODS: Observational cohort study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, Cox and logistic regression analyses by smoking status (current/never/previous) were calculated for treatment adherence and BASDAI 50%/20 mm-response. Additional stratified analyses were performed for gender and TNFi-type.RESULTS: Of 1576 AS patients included in the study, 1425(90%) had known smoking status (current/never/previous: 43%/41%/16%). The median follow-up time was 2.02 years (IQR 0.69-5.01). At baseline, current smokers compared with never smokers had longer disease duration (4 years (1-12)/2 years (0-10)), higher BASDAI (61 mm (47-73)/58 mm (44-70)), BASFI (53 mm (35-69)/46 mm (31-66)) and BASMI (40 mm (20-60)/30 mm (10-50)) scores (all P < 0.01). Current and previous smokers had shorter treatment adherence than never smokers (current: 2.30 years (1.81-2.79) (median (95% CI)); previous: 2.48 years (1.56-3.40), never: 4.12 years (3.29-4.95)), P < 0.0001). Similar results were found in multivariate analyses (current versus never smokers, HR 1.41 (95% CI 1.21-1.65), P < 0.001), most pronounced among men. Current smokers had poorer 6 months' BASDAI50%/20 mm-response rate than never smokers (42%/58%, P < 0.001). In multivariate analyses, current smokers had lower odds of achieving BASDAI50%/20 mm-response than never smokers, both overall (OR 0.48 (95% CI 0.35-0.65), P < 0.0001) and for the different TNFi-types (adalimumab 0.45 (0.27-0.76)/etanercept 0.24 (0.10-0.61)/infliximab 0.57 (0.34-0.95)).CONCLUSION: In this study of TNFi-treated AS patients in clinical practice, current and previous smokers had significantly poorer patient-reported outcomes at baseline, shorter treatment adherence and poorer treatment response compared with never smokers.

Background Studies on the impact of smoking among patients with akylosing spondylitis (AS) treated with tumor necrosis factor alpha inhibitor therapy (TNFi) are few. Objectives To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses among patients with AS initiating the first TNFi in routine care. Methods Observational cohort study based on the Danish nationwide DANBIO registry. Patient inclusion was from year 2000 until January 1st 2014. Kaplan-Meier plots, logistic and Cox regression analyses by smoking status (current/previous/never smoker) were calculated for treatment adherence and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50%/20mm-response. Additional stratified analyses were performed according to gender and TNFi-subtype. Results Among 1576 AS patients included in the study, 1425 (90%) had known smoking status (43% current, 40% never and 16% previous smokers). Median follow-up time was 2.02 years (IQR 0.69-5.01). At baseline, current smokers had longer disease duration (4 years (1-12)/2 years (0-10)), higher BASDAI score (61 mm (47-73)/58 mm (44-70)), Bath ankylosing spondylitis function index (BASFI) (53 mm (35-69)/46 mm (31-66)) and Bath ankylosing spondylitis metrology index (BASMI) (40 mm (20-60)/30 mm (10-50)) than never smokers (all p Conclusions In this study of AS patients treated with TNFi in clinical practise, current smokers had poorer baseline patient-reported outcomes, shorter treatment adherence and poorer treatment response compared to never smokers. Acknowledgements Thank you to all the departments of rheumatology in Denmark for reporting to the DANBIO registry Disclosure of Interest B. Glintborg: None declared, P. Hojgaard: None declared, M. Hetland: None declared, S. Chrysidis: None declared, J. Espesen: None declared, M. Holland-Fischer Consultant for: Roche, Abbvie, Speakers bureau: UCB, MSD, F. Johansen: None declared, J. Jensen: None declared, I. M. Hansen: None declared, T. Hansen: None declared, G. Kollerup Speakers bureau: MSD, N. S. Krogh: None declared, A. G. Loft Consultant for: MSD, AbbVie, Speakers bureau: MSD, Pfizer, AbbVie, T. Lorenzen: None declared, P. Mosborg: None declared, C. Nilsson: None declared, H. Nordin: None declared, S. Oeftiger: None declared, R. Pelck: None declared, C. Rasmussen: None declared, B. Unger: None declared, L. Dreyer: None declared

Background According to national guidelines issued in 2015, a non-medical switch from originator infliximab (IFX) (Remicade) to biosimilar Remsima was conducted in all Danish patients with inflammatory rheumatic diseases treated in routine care. Objectives To investigate 3 months9 clinical outcomes in Remicade-treated patients (pts) with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthrits (SpA) who switched to Remsima and were monitored prospectively in the DANBIO registry. Methods Disease activity at 3 mths before switch (pre-switch), at the switch and after 3 mths (70–120 days) (post-switch) and changes over time (Δpre-switch and Δpost-switch) were calculated. Disease flare was defined as ΔDAS28≥1.2 (RA/PsA) or ΔASDAS≥1.3 (SpA). Reasons for withdrawal (adverse events (AE), lack of effect (LOE) or other) were registered. Results 647 of 693 switching pts (300 RA, 96 PsA, 219 SpA, 32 other) had available data (52% women, age (median (IQR) 56 (45–66) yrs)). Prior Remicade treatment duration was 6.7 (4.1–9.4) yrs and in 77% it was the first biological treatment. Remsima dose was in RA+PSA 3.3 (3.0–4.8) mg/kg every 7 (6–8) wks and in SpA 4.8 (3.6–5.1) mg/kg every 6 (6–9) wks. Concomitant MTX was given in 69% (RA+PsA)/25% (SpA). Median follow-up time was 139 (98–160) days. Disease activity remained largely unchanged 3 months prior to vs. after the switch (Table). The proportion of patients with disease flare pre-/post switch was 10%/10% (RA+PsA) (p=1.0) and 10%/0% (SpA) (p=1.0) (related samples McNemar test). Overall, 45 ptts (7%) stopped Remsima treatment during follow-up (AE 16 (allergic 3, infection 2, rash 2, unspecific 9), LOE 20, remission 3, cancer 2, other 4). Prior Remicade treatment duration in these patients was 5.9 (3.5–9.1) yrs. Conclusions In 647 patients with inflammatory rheumatic diseases treated with Remicade for >4 years, disease activity was largely unaffected in the majority of patients 3 months after non-medical switch to biosimilar Remsima and comparable to the fluctuations observed in the 3 months prior to the switch. However, several patients (∼6%) stopped treatment due to LOE or AE. This warrants further investigation before such a non-medical switch can be recommended. Disclosure of Interest None declared

Background There is an increasing use of vascular ultrasound (US) as a diagnostic tool in Giant Cell Arteritis (GCA) internationally. Therefore, it is of great importance to develop and standardise examination technique, machine settings and offer proper training of ultrasonograhers to ensure a high level of expertise in order to obtain reliable results Objectives The aim of this study is to evaluate a specific vascular US training program in GCA diagnostic. Methods Patients suspected for GCA were US evaluated by five rheumatologists with long-standing experience in musculoskeletal US who were trained by the following program: Participation at the International Workshop on ultrasound in Large Vessel Vasculitis & Polymyalgia Rheumatica in Kristiansand, Norway (5 hours theoretical and 10 hours supervised hands-on education). Later, further training and standardisation was obtained at a two days workshop (Esbjerg, Denmark) including training with both healthy persons and GCA patients (totally 6 hours of supervised hands-on trainings and 1 hour of image evaluation). High-end equipment (Hitachi Preirus & GE logic-9E), with comparable settings and standardized examinations methods was used. As part of an ongoing study the following arteries were evaluated bilaterally: temporal artery (common, pariental and frontal branch)(AT), the facial artery (AF), the common carotid artery (AC)and the axillary artery (AA). Both still images in two planes and films were recorded. Images were subsequently evaluated first by the performing ultrasonographer and after by a blinded external expert (gold standard). Detailed feedback on the US technique was given to the performing ultrasonographer by the external expert. US was considered positive when a homogeneous hypoechoic thickness >1.5 mm in AC and >1mm in AA, in transverse and longitudinal view was observed. For the AT and AF, the halo sign (hypoechoic arterial wall swelling in transverse and longitudinal view) and/or positive compression-sign (impaired compression) was considered a sign of vasculitis Results Twenty patients suspected for GCA were enrolled in a period of 8 months in 3 Danish centres (Esbjerg, Glostrup, Silkeborg) In all ten patients with positive Temporalis Artery Biopsy (TAB) was found US vasculitis in AT according to both external expert and performing ultrasonographer. Arteritis in AA was found in 3/10 according to external expert and in 4/10 patients according to performing ultrasonographer In the rest 10 patients with negative TAB were no sign of US vasculitis in AT and AF (external expert) and according to performing ultrasonographer there was US AT vasculitis in 1/10. Arteritis in the extracranial arteries was found in 2 patients (bilateral in AA) according to both expert and ultrasonographer. Totally, 240 vessels were scanned and vasculitis changes were observed in 58 vessels (expert) and in 55 vessels (performing ultrasonographer). The inter-observer agreement between the performing ultrasonographer and the blinded expert was excellent in all 3 centre (table) Cohens kappa-coefficient Esbjerg k=0,89,Glostrup k=0,91 & Silkeborg k=0,82. Conclusions The above mentioned educational program showed excellent results in diagnostic of GCA and excellent interobserver agreement. It could be considered as a teaching model to vascular ultrasound in the diagnosis of GCA Disclosure of Interest None declared

Background Fibromyalgia (FM) exists in a substantial number of patients with rheumatoid arthritis (RA) (approx. 15%), who have higher disease activity as measured by DAS-28, than RA patients without concomitant FM. It is important to understand if there is an association between active inflammation on joint level and FM symptoms in RA patients Objectives In this study, we examined the relation between joint inflammation and FM symptoms in RA patients. We hypothesized that there is no correlation between the severity of inflammation on joint level and FM symptoms. Methods In a period of 8 months, RA patients (US-RA group) who were candidates to biological treatment underwent ultrasound (US) examination (Hitachi Preirus,14 or 18 MHz linear transducer) before initiation of biological treatment. The patients underwent screening for fibromyalgia (FM) using The Modified 2010 American College of Rheumatology (ACR) Diagnostic Criteria. Two experienced ultrasonographers (SC, AC) blinded to the DAS-28 and FM results performed the UL examination, while experienced nurses, blinded on US and FM results performed the DAS28 calculation. In a study made at the same period of time in our department we found that 13 RA patients in established biological treatment were diagnosed as having concomitant FM (RAF group). These patients were in a stabile treatment during the examination time and there was calculate DAS-28 in the same way as above. The comparisons between US-RA and RAF groups were performed by unpaired t-test after confirming normal distribution of data. Results We included 13 patients in the US-RA group. They had at least two joints with high inflammation (Grey scale synovitis grade II and Colour Doppler grade II as minimum). They were screened for FM and only one of these patients fulfilled the Modified 2010 ACR diagnostic criteria. Three months later all patients were in DAS remission/low disease activity, except the patient with concomitant FM, who still had moderate high DAS because of many tender joints and high VAS-GH. We also compared the US-RA group with RAF group and there was no significant difference in age, gender, disease duration & seropositivity. The rest of comparisons between the two groups are shown in Table 1. Conclusions We did not find evidence that RA patients with high inflammation on joint level have higher rates of FM. Biological naive RA patients (US-RA group) with high level of joints inflammation as confirmed by US had less severe subjective symptoms (VAS & HAQ) compared to RAF patients in a stabile biological treatment phase and without swollen joins. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5237