Abstract: Calcium pyrophosphate deposition disease (CPPD), also known as pseudogout, is a prominent member of the crystal deposition diseases much like gout where urate crystals are the pathogens. CPPD is differentiated from chondrocalcinosis, a radiographic finding showing joint calcification, which may or may not be relevant for the clinical picture of patients (1). Objectives: To determine the prevalence of chondrocalcinosis in different inflammatory rheumatic diseases. Methods: In a retrospective cross-sectional study design we reviewed the records of not established new patients presenting to our center between 1.1.2016 and 31.12.2018. Based on the availability of radiographs of hands and feet, 514 patients were identified including 181 patients with CPPD, 273 with rheumatoid arthritis (RA), 143 seropositive (52.4%) and 130 seronegative, 30 with gout and 30 with polymyalgia rheumatica (PMR). Radiographs of hands and feet were available from all patients, of the knee in 376 cases. All images were read by two experienced readers with no access to clinical data. Results: Almost all patients had a short disease duration of 〈 1 year. In patients diagnosed with CPPD all radiographs showed chondrocalcinosis (93%) at some location, mostly in the hands. This was different in seronegative (36.5%) and seropositive (30.3%) RA. Chondrocalcinosis was found less frequently also in gout (18.8%) and PMR (12.5%). More data are shown in the Table 1. Radiographic chondrocalcinosis was present in more than one joint in 36.6% patients with CPPD, in 11.9% in seropositive and in 17.3% in seronegative RA. Patients with CPPD were older and had acute attacks more often than RA patients. While RA patients were more frequently on methotrexate (MTX), patients with CPPD were more often on colchicine. Table 1. Radiographic and clinical features of the examined patients Conclusion: There were a lot of similarities but also some important differences between patients with CPPD and RA with no major differences between seropositive and seronegative RA. Of interest, radiographic chondrocalcinosis was seen in more than a third of RA patients. Importantly, clinical symmetry of arthritis and involvement of hands did not differentiate between CPPD and RA, mainly the acuteness of attacks did. Co-occurrence of both diseases was frequently observed. There was no major difference between seropositive and seronegative RA. References: [1]Rosenthal AM, Ryan LM. N Engl J Med. 2016 Disclosure of Interests: None declared.

Abstract: The clinical efficacy of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) is well established but its effect on new bone formation is still unclear (1). Positron emission tomography (PET) using bone-seeking 18 F-Fluoride [18F]F in combination with magnetic resonance imaging ([18F] F /MRI) has been shown to depict not only bone marrow edema (BME) but also shows the quantity of tracer uptake in the late phase of perfusion suggestive of remodeling and osteoblastic activity, not only in radiographic axSpA (r-axSpA) (2). Objectives: Assess the effect of TNFi on bone remodeling processes in the axial skeleton of r-axSpA patients using [18F]F/MRI prior (baseline, BL) and 4 months after (follow-up, FU) treatment. Methods: Patients (11 male, 5 female, mean age 38.6±12.0 years) with clinically active r-axSpA (BASDAI 〉 4, failure of NSAIDs, no previous biologics) prospectively underwent 3-Tesla and [18F]F PET/MRI (40 minutes after injection of a mean activity of 157 MBq [18F] F). Images of the SIJ (n=16 patients) and the whole spine (n=10 patients) were performed at BL and FU. Three readers (1 for [18F]F/MRI and 2 for conventional MRI) evaluated all images independently and blinded to timepoint allocation. Only lesions on which all readers agreed on were used for further analyses. Inflammation (bone marrow edema, BME), structural lesions (fat deposition (FD), sclerosis, erosions and ankylosis) and focal [18F] F uptake were recorded on the level of SIJ (SIJ-Q) and vertebral quadrants (V-Q), with each SIJ or vertebral body consisting of 4 VQs (superior and inferior sacral and iliac for the SIJ, and superior and inferior, anterior and posterior for the vertebral bodies). Results: A total of 128 SIJ-Q and 920 VQs were analyzed at both BL and FU. In the SIJs, 75 (58.6%), 120 (93.8%), 69 (53.9%), 99 (77.3%) and 16 (12.5%) SIJ-Q showed BME, FD, sclerosis, erosions and ankylosis, while 111 (86.7%) SIJ-Q showed focal [18F]F-uptake at BL. Association with increased [18F] F-uptake was found most frequently in SIJ-Q with BME (70/75 SIJ-Q, 93.3%), sclerosis (65/69 SIJ-Q, 94.2%) and FD (105/120 SIJ-Q, 87.5%). At FU, 37 SIJ-Q still showed BME (improvement by 50.7%), while almost no changes were observed in chronic lesions. In comparison, improvement of focal [18F]F-uptake was found in all lesion combinations, with improvement of focal [18F] F-lesions associated with BME by 62.9%, with sclerosis by 33.8% and with FD by 22.9% of SIJ-Q. In the spine, only 41 (4.5%), 61 (6.6%), 14 (1.5%) V-Q showed BME, FD and sclerosis, respectively, while 77 V-Q (8.4%) showed focal [18F]F-uptake. An association to increased [18F] F-uptake was found most frequently with sclerosis (7/14 V-Q, 50%) and FD (25/61 V-Q, 41%). At FU, 12 V-Q still showed BME (improvement by 70.7%), while, similar to SIJ, almost no changes were observed in the chronic lesions. The largest improvement was found in focal [18F] F-lesions associated with BME 81.8% and with FD by 22.9% of V-Q. Conclusion: In this first prospective study on whole spine and SIJ [18F]F/MRI in patients with r-axSpA, a significant decrease of osteoblastic activity was observed over 4 months of continuous anti-TNF treatment. The effect of treatment was observed not only at sites with inflammatory lesions (BME) but also at sites with pre-existing chronic structural lesions, while some osteoblastic activity remained visible at 4 months. These data support a short-term effect of anti-TNF treatment on osteoblastic activity, while the long-term effects need to be further studied. References: [1]Van der Heijde D et al, Ann Rheum Dis 2017 [2]Buchbender C et al, J Rheumatol 2015 This work was supported by an unrestricted Grant by MSD GmbH, Germany Disclosure of Interests: Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Styliani Tsiami: None declared, Christoph Rischpler: None declared, Nils-Martin Bruckmann: None declared, Wolfgang Fendler: None declared, Julian Kirchner: None declared, Ken Hermann: None declared, Lino Sawicki: None declared, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma

Abstract: Chronic back pain (CBP) of the inflammatory type (IBP) is frequently reported in axSpA but also in the general population. Objectives: We evaluated a recently proposed two-step referral system for early recognition of axSpA (concentrating on patients ≤45 years with chronic back pain who present with buttock pain, improvement by movement, psoriasis, positive testing for HLA-B27) in primary care and compare it to other combinations of symptoms and SpA-related items. Methods: Consecutive patients ≤45 years who presented in PC to general practitioners or orthopedic surgeons working in PC with back pain lasting ≥2 months who had not been diagnosed before received questionnaires (Q1) relevant for the referral process. Thereafter, the PC physician asked the same questions in a separate questionnaire (Q2), including the decision on HLA-B27 testing. All patients were then referred to two experienced rheumatologists in a tertiary center who performed a complete workup including clinical, laboratory and imaging with radiographs and magnetic resonance imaging (MRI) examinations before their final diagnosis of axSpA or non-SpA (Q3). Results: A total of 320 patients (mean age 35.9±10.3 years) was recruited. The proposed referral strategy (prS) was fulfilled by 127 patients in Q1 (39.7%), 160 in Q2 (50%), 102 by both, Q1 and Q2 (31.9%), and 83 with either Q1 or Q2 (25.9%). Overall, 47 patients were diagnosed with axSpA by the rheumatologist at Q3 (14.7%), 66% of which were male, mean age 34.7±10.1 years, 70.2% HLA-B27 positive, mean CRP 0.8±1.4mg/dl, mean ASDAS 3.2±0.8, mean BASDAI 5.1±2.0. Of these, 37 patients had fulfilled the prS in Q1 or Q2 (78.7%), and 31 in both Q1 and Q2 (66%), respectively. In the latter, the HLA-B27 prevalence was significantly higher (27/31, 87.1%) as compared to patients diagnosed with axSpA at Q3 but who did not fulfill the prS in Q1 and Q2 (5/16, 31.3%) (p 〈 0.001). The sensitivity and specificity of the prS was 78.7% and 69.2% in Q1, 78.7% and 62.2% in Q2, and in both, Q1 and Q2, 66% and 74%, respectively. AxSpA patients correctly identified by the prS in Q1 and Q2, were significantly more frequently positive for HLA-B27 and CRP and fulfilled more frequently the ASAS definition of inflammatory back pain in Q3. Conclusion: A simple two-step referral strategy using a combination of clinical features for identifying axSpA patients in PC without laboratory and imaging examinations was confirmed in a large population from daily practice. This strategy performed well as selection for referral at the patient and PC physician level. This work was supported by an unrestricted Grant by Novartis Pharma GmbH, Germany Table 1. OR (95% CI ) Overall P value Inpatient stay duration 0.87 (0.82, 0.93) 〈 0.001 Opioids prescribed at discharge 0.23 (0.09, 0.55) 0.001 Patient’s location before admission: 0.02 Home 1.0 (réf.) A & E Department 0.25 (0.10, 0.65) Other Department 0.35 (0.05, 2.53) Charlson comorbidity index 0.76 (0.82, 0.93) Main diagnosis (only significant conditions displayed): 0.03 Low back pain, sciatica 1.0 (réf.) Abarticular conditions 0.03 (0.002, 0.47) Osteoporotic fracture 0.17 (0.05, 0.52) Predictors of home discharge. Multivariate logistic regression analysis. N=223. Disclosure of Interests: Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Styliani Tsiami: None declared, Doris Morzeck: None declared, Kirill Fedorov: None declared, Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma

Abstract: The availability of biosimilars has created a financial incentive to encourage non-medical switching if cheaper products are on the market. In patients with chronic inflammatory rheumatic diseases (CIRD), we have previously reported a relatively high retention rate after switching from originator etanercept to its biosimilar. However, this has been different in other studies and the reasons for non-adherence are poorly understood. Comorbidity has recently gained much attention in patients with CIRD and might be a reason for non-adherence. Objectives The aim of this study was to analyse the effectiveness and safety of systematic non-medical switching from originator adalimumab (ADA) to ADA ABP501 biosimilar (ABP) over 6 months in patients with CIRD and to investigate the influence of comorbidities on retention rates. Methods Patients with CIRD on originator ADA who switched to ABP subsequently from October 2018 onwards were identified from a large routine database and then followed for 6 months. The presence of comorbidities and disease characteristics as well as measures of disease activity, physical function and changes in treatment were documented at baseline (the time of switching from originator ADA to ABP), and at months 3 and 6. Longitudinal data including information on the clinical efficacy and safety of ABP, and the reasons for discontinuation were documented. Results A total of 111 CIRD patients on treatment with originator ADA were switched to the biosimilar ABP (Table 1). More than half of the patients (62%) had a Charlson comorbidity score of 0, though there were differences between disease subtypes. RA patients were comparatively older (mean age 65 years) and had the highest mean Charlson score (1.8). Treatment retention varied only slightly between patients with a Charlson score of 0 and those with ≥0 (Figure 1). In both groups, the majority of patients (90% vs 95%) continued therapy with ABP, while only a small proportion either switched back to originator ADA (6% vs 5%), switched to a different biologic (3% vs 0%), or dropped out (1% vs 0%). The main reason for back switch was the occurrence of adverse events, mostly subjective complaints, most frequently pain. Patients with a Charlson comorbidity score 〉 0 tended to have poorer scores in trajectories of scores for disease activity and physical function stratified by disease subtype. Figure 1. Treatment retention after 6 months stratified by the Charlson comorbidity score Table 1. Patients and disease characteristics RA axSpA PsA Other N=23 N=68 N=15 N=5 Age (years), mean (SD) 65.1 (12.0) 47.3 (13.1) 51.1 (11.2) 41.8 (14.2) Women 60.9% (14) 32.4% (22) 53.3% (8) 40.0% (2) Disease duration (years), median (IQR) 4.0 (3.0-8.0) 5.0 (2.0-8.0) 4.0 (2.0-13.0) 7.0 (4.0-7.0) Duration originator ADA therapy (month), mean (SD) 43.8 (28.6) 39.4 (26.9) 34.7 (29.0) 60.9 (27.7) Charlson score, mean (SD) 1.8 (2.1) 0.6 (1.1) 0.7 (1.2) 0.2 (0.4) Gastroenterological comorbidities 26.1% (6) 22.1% (15) 6.7% (1) 0 Hepatic comorbidities 17.4% (4) 2.9% (2) 13.3% (2) 0 Hematological conditions 8.7% (2) 2.9% (2) 13.3% (2) 0 Cardiovascular comorbidities 60.9% (14) 32.4% (22) 33.3% (5) 60.0% (3) Neurological and psychological comorbidities 8.7% (2) 17.6% (12) 33.3% (5) 0 Metabolic comorbidities 21.7% (5) 7.4% (5) 26.7% (4) 40.0% (2) Osteoporosis 43.5% (10) 11.9% (8) 6.7% (1) 20.0% (1) Lung diseases 21.7% (5) 8.8% (6) 0 40.0% (2) Skin diseases 26.1% (6) 26.5% (18) 80.0% (12) 20.0% (1) Eye diseases 8.7% (2) 23.5% (16) 6.7% (1) 60.0% (3) Kidney diseases 13.0% (3) 10.3% (7) 0 40.0% (2) Conclusion Comorbidity had no influence on the biosimilar retention rate after 6 months in this study but the majority of patients did not have Charlson scores 〉 0. However, disease activity and physical function tended to be worse among CIRD patients with comorbidity. Cardiovascular disease and osteoporosis were more often present in RA patients than in axSpA or PsA patients, while neurological and psychological comorbidities were more often observed in the latter. Disclosure of Interests Imke Redeker: None declared, Stefan Moustakis: None declared, Styliani Tsiami: None declared, Xenofon Baraliakos Speakers bureau: Abbvie, Pfizer, MSD, UCB, Novartis, Lilly, Galapagos, Hexal, Paid instructor for: Abbvie, Pfizer, MSD, UCB, Novartis, Lilly, Galapagos, Hexal, Consultant of: Abbvie, Pfizer, MSD, UCB, Novartis, Lilly, Galapagos, Hexal, Grant/research support from: Abbvie, Pfizer, MSD, UCB, Novartis, Lilly, Galapagos, Hexal, Ioana Andreica Speakers bureau: UCB, MSD, Novartis, Abbvie, Lilly, Janssen, SOBI, Consultant of: Lilly, Novartis, Galapagos, Amgen, Takkeda, SOBI, Grant/research support from: Lilly, Bjoern Buehring Speakers bureau: UCB, Amgen, Gilad/Galapagos, Biogen, Sanofi/Genzyme, Consultant of: UCB, Theramex, Gilead/Galapagos, Amgen, Abbvie, Juergen Braun Speakers bureau: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Uta Kiltz Speakers bureau: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, Pfizer.

Abstract: A fast response to non-steroidal anti-inflammatory drugs (NSAIDs) is an important finding in the evaluation of clinical findings within the items comprising the ASAS classification criteria but also for the treatment decision for escalation to a bDMARD in patients with axial spondyloarthritis (axSpA). However, the differentiation of NSAID responses between patients with axSpA and degenerative or unspecific back pain is still unclear. Objectives To study the differences in the velocity and magnitude of NSAID response velocity in patients with established bDMARD naïve axSpA vs. patients with other, non-inflammatory reasons of back pain. Methods Patients with axSpA without degenerative reasons for back pain or patients with degenerative or unspecific back pain presenting due to high levels of back pain (NRS≥4/10) were consecutively recruited. Assessments included clinical examination, laboratory tests and MRI of the lumbar spine. Previous NSAID intake was allowed only if it was taken in low doses without showing a clinical response, otherwise patients were NSAID naïve. Upon study inclusion, patients were treated with the maximum possible dose of an NSAID that they have reported to tolerate in lower doses in the past, independent of whether this was a Cox-2 inhibitor or a non-coxib. Assessment of response was performed using a standardized questionnaire after 2, 6, 12, 24, 36, 48 hours and after 1, 2 and 4 weeks. Any NSAID response was defined as improvement of pain 〉 2/10 points and a good response to NSAIDs as an improvement 〉 50% from the initial status. Results A total of 68 patients with axSpA, 107 patients with degenerative back pain and 58 patients with unspecific back pain were included. The mean age was 42.7±10.7, 51.2±11.3, and 45.8±10.0 years, the main symptom duration 15.1±11.1, 16.1±12.6, and 11.9 ±10.1 years and the proportion of males was 57.4%, 19.6%, and 19.0% respectively. Inflammatory back pain was reported by 42 (75%), 48 (57.8%), and 29 (60.4%) patients, respectively and the mean pain score was 6.2±2.3,6.7±1.8, and 6.2±1.8, respectively. In axSpA, the mean BASDAI and BASFI scores were 5.5±1.8 and 4.5±2.5, respectively. There was no difference in the cumulative response to NSAIDs between all three diagnoses, with an overall proportion of 27%-30% of patients showing improvement. However, better but not faster responses were found for the subgroups of patients with nr-axSpA (Figure 1) and for the male patients in the entire axSpA group, while axSpA patients with systemic inflammatory activity defined by increased CRP showed lower rates of response as compared to non-inflammatory reasons of back pain diagnoses. All other subanalyses did not reveal any differences between axSpA patients and other non-inflammatory reasons of back pain. Figure 1. Conclusion In this prospective evaluation, the generally proposed better response of axSpA patients to treatment with high doses of NSAIDs as compared with non-inflammatory back pain was not confirmed, although the overall rate of responders was similar to previously reported rates. On the other hand, better responses were found in patients treated in the early (nr-axSpA) stage and in male patients. axSpA patients with increased CRP values showed lower rates of response. Disclosure of Interests None declared

Abstract: Diagnosis and treatment of PsA and axSpA is often delayed due to missing clear diagnostic criteria and limitations in resources for referral to rheumatologist including high numbers of incorrect referrals. Primary care is usually provided by either general practitioner, dermatologists, or orthopedics. Clinical discriminators with a high specificity for rheumatic conditions include morning stiffness (MST; peripheral or axial, 〉 30min). Artificial intelligence (AI) and natural language processing (NLP) methods offer algorithms for learning systems to recognize disease associated terms and classify clinical phenotypes using large data sets that may support early identification of patients with suspected diagnosis of PsA or axSpA. Objectives AI and NLP methods are used to identify patients with typical attributes for inflammation by using morning stiffness as one potential discriminating pattern, which can be detected automatically and might help to prioritize referral for rheumatologist appointments. Methods Within a multicentre observational study, patients with visits at the rheumatologist with a suspected diagnosis of PsA or axSpA from the referral primary care provider were recruited. All data on clinical examinations and findings were collected and evaluated by rheumatologists in focus on criteria for diagnosis of PsA/axSpA (gold standard for evaluation). Unstructured text from the patient history was used to extract diagnosis-relevant characteristics. The information extraction algorithms used NLP models to detect expert curated “morning stiffness” (MST) keywords and puts them into a contextualized framework that allows to capture possible negations. Results A total of 116 patients were recruited (73 female, 63%) with a median age of 42 (IQR: 34-54). 51 patients were referred as axSpA (44%) and 60 as PsA (52%) by primary care providers. After preselection for PsA and axSpA patients, we observed a 23% rate of referrals without rheumatic diagnosis. Only 7.1% of patients were admitted without signs of MST, 29% with axial MST, 35% with peripheral MST and 28% with both MST types. Average morning stiffness duration was recorded as 35 minutes; patients with a finally confirmed rheumatic diagnosis had a higher average MST duration reported (36 minutes) compared to patients without a confirmed diagnosis. Our AI assisted extraction of MST identified MST in 82.7% of patient history texts. In 75% NLP methods correctly identified the negation of MST symptoms (6 of 8), and 94% of MST was detected when both axial and peripheral joints were affected (30 of 32). Manual inspection of 20 patient history reports where MST was not detected by our automated algorithm revealed that 17 reports did not contain information about MST and three mention unspecific early morning discomfort, without mention of MST. Conclusion The high rate of correct detection of MST from patient history text using NLP methods allowed us to assess the potential for NLP models to support automated analysis of patient reports to facilitate intelligent patient referral. Acknowledgements We thank the Fraunhofer Excellence Cluster for Immune-Mediated Diseases CIMD for the financial support. Disclosure of Interests None declared

Abstract: Decrease of proteoglycan is the initiating stage of post-inflammatory tissue degradation. Sodium MRI is promising great potential for identification and monitoring of proteoglycan changes in tendons and cartilage associated with inflammatory and degenerative musculoskeletal diseases, where the Achilles tendon is frequently affected. Objectives Proof-of-concept study to examine the usage of sodium MRI in quantifying sodium concentrations in the Achilles tendon in healthy volunteers. Methods Sodium ( 23 Na) MR imaging of the Achilles tendon together with established proton ( 1 H) MRI sequences were performed in 10 healthy volunteers (6 males, 4 females, age 29 ± 9 years) using a dual-tuned 23 Na/ 1 H surface coil (RAPID Biomedical GmbH, Würzburg-Rimpar, Germany). Imaging was performed using a 3D density adapted radial sequence [1] providing sufficient signal-to-noise ratio for sodium imaging. Reference tubes on the backside of the coil were used to enable assessment of sodium concentration from sodium signal-to-noise ratio maps. Sodium concentrations were determined for tendon insertion into calcaneus bone (INS), middle portion of the tendon (MID) and muscle-tendon junction (MTJ) and for the whole Achilles tendon. Statistical differences were analysed by Wilcoxon test. Results Sodium concentrations c [mM] of the Achilles tendon could be quantified in all 10 (exemplary selected volunteer is shown in Figure 1). Significantly higher sodium concentrations were obtained in INS compared to MID (p=0.002) and MTJ (p=0.002) and in MID compared to MTJ (p=0.037). The average sodium concentration of the whole Achilles tendon was 57.23±17.69 mM with only minor outliers in this healthy population. Figure 1. Sodium concentrations of the Achilles tendon. Highest sodium concentrations c(mM) were observed at the tendon insertion into calcaneus bone (INS), whereas lower concentrations were measured in the middle portion of the tendon (MID) and muscle-tendon junction (MTJ). Conclusion Performance of quantitative sodium imaging of the Achilles tendon in a high-field MRI machine is feasible for assessing sodium concentrations, a surrogate biomarker for proteoglycan content. Molecular MR studies investigating changes in the proteoglycan content of the Achilles tendon in patients with inflammatory and degenerative musculoskeletal diseases could support early diagnosis or therapy monitoring in the future. References [1]Nagel et al. Magn Reson Med (2009) 62(6):1565-73. DOI: 10.1002/mrm.22157 Disclosure of Interests None declared

Abstract: The preselection of patients with suspicion of an inflammatory rheumatic disease is not easy for general practitioners and orthopedists. In countries with a limited number of practicing rheumatologists waiting lists are often long, since a full rheumatologic examination often needs a long consultation time. Objectives To test the performance of an early triage strategy for early identification of patients with inflammatory rheumatic diseases. Methods Prior to the SARS-CoV 2 pandemic, physicians caring for patients contacting a tertiary rheumatologic cente were first contacted by a health-care professional (HPR) who offered an appointment the timing of which was based on the symptoms reported (Step 1). Patients were then seen by a rheumatologist who, within a 10-minute consultation (Step 2), shortly examined the patient to determine the urgency of a planned full work up. The main outcome of the study was the comparison between the initial assessment and the final expert diagnosis (Step 3). Results Within 9 months, physicians caring for 1.180 patients contacted the hospital, 972 of whom kept their appointment (82.4%). Most patients were transferred by GPs (73.1%) and orthopedists (22.1%). The mean time between Step 1 and Step 2 was 10.4 days, while 6.2% of patients were seen within 4 days, 24.4% within 7 days and 69.3% within 12 weeks. Only 36 patients (3.7%) of patients had an already established rheumatic disease. Complaints lasting between 0-4 weeks were reported by 69 (7.1%), of 〉 4-12 weeks by 100 (10.3%), and of 〉 12 weeks by 973 (82.6%) patients. Almost 90% of patients reported a pain intensity 〉 4/10 (NRS) for 〈 2 weeks. An elevated CRP was found in 207 patients (24.5%). Prior treatment with glucocorticoids was reported in 163 (16.8%) and with NSAIDs in 730 (75.1% of) patients. The confirmed diagnosis at Step 3 was rheumatoid arthritis in 127 (13.1%), spondyloarthritis including psoriatic arthritis in 72 (7.4%), systemic diseases including connective tissue diseases in 112 (11.5%), vasculitides in 41 (4.2%), and crystal arthropathy in 38 (3.9%) patients, while 38 (3.9%) had an infection, a malignancy or a differential diagnosis such as Raynaud’s phenomenon or sicca syndrome. Degenerative joint diseases (n=254; 26.1%) and non-inflammatory soft tissue syndromes such as fibromyalgia (n=369; 38%) accounted for more than half of the patients. Conclusion This study describes the performance of a standardized triage system hereby confirming the need for an early identification and preselection of patients with rheumatic musculoskeletal symptoms, including involvement of HPRs in the initial phase of contact. Based on the results, three patients with musculoskeletal complaints had to be examined in order to identify one patient with an inflammatory rheumatic disease. Disclosure of Interests None declared

Abstract: There is increasing evidence of the pathogenetic role of monocytes and neutrophils in AS, while the neutrophil-to-lymphocyte ratio correlates with disease activity (1). Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF) is a growth factor for both myeloid lineages and a potent pro-inflammatory cytokine activating myeloid cells, including pro-inflammatory M1 macrophage polarization, production of TNF and other cytokines, and promoting osteoclastogenesis (2). It signals through the JAK-STAT pathway. Objectives To measure serum GM-CSF together with markers of bone metabolism in patients with AS before and after anti-TNF treatment. Methods The study included patients with the clinical diagnosis of AS (also fulfilling the 1984 modified NY criteria) with increased disease activity despite treatment with NSAIDs, all being eligible for treatment with a biologic DMARD. Decision for treatment with a TNF-inhibitor was made by the treating rheumatologist. Healthy donors were sampled as controls. Serum was collected before (baseline, BL) and after 4-6 months (follow-up, FU) of anti-TNF treatment and the following molecules were measured using ELISA: GM-CSF, Sclerostin (SOST) and Dickkopf-1 (Dkk-1). Results Twelve patients with AS (7 males, 5 females, median age 37 years, range 22-52) with a median disease duration of 1 year (range 0.5-25) and 16 age- and sex-matched controls were included. At BL, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7. At FU the mean BASDAI decreased to 4.1±1.7 and ASDAS decreased to 2.2±0.6. At BL, AS patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not significantly affect GM-CSF, Dkk-1 or SOST levels (p 〉 0.05 for all comparisons at FU vs baseline). Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), negatively with age (r=-0.68, p=0.018), but not with disease duration (r=-0.27, p=0.400). No correlations were identified between bone markers (Dkk-1, SOST) and GM-CSF or disease activity indices. Conclusion GM-CSF is increased in patients with active AS, particularly in younger ages, and strongly correlates with disease activity, but not with disease duration. In contrast, TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway in AS that could be responsible for residual inflammation during TNF blockade, but also explain the efficacy pathway of treatment with JAK inhibitors. References [1]Sen R, Kim E, Cheng E et al. A Tough Cell: The Argument for a Biomarker of Clinical and Imaging Outcomes in Spondyloarthritis: The Neutrophil Lymphocyte Ratio and the Platelet Lymphocyte Ratio [abstract] . Arthritis Rheumatol. 2021; 73 (suppl 10). [2]Crotti C, Agape E, Becciolini A et al. Targeting Granulocyte-Monocyte Colony-Stimulating Factor Signaling in Rheumatoid Arthritis: Future Prospects. Drugs. 2019 Nov;79(16):1741-1755 Acknowledgements There are no acknowledgements to declare. Disclosure of Interests None declared