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ObjectivesTo establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies.MethodsA multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence.ResultsRecommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare.ConclusionWe have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

Background:Intra-articular therapy (IAT) is routinely used in rheumatic and musculoskeletal diseases (RMDs). In order to improve the effectiveness and safety of IAT, it is essential to understand patients’ perceptions and needs.Objectives:To assess the perspective of persons who have experienced IAT, including perceptions on benefits and safety.Methods:A steering committee (including a patient research partner) prepared a 44-item questionnaire based on the information needs of a Taskforce on IAT in adult patients with RMDs. The questionnaire was translated into 11 languages and disseminated via EULAR PARE associations and social media. Persons who had experienced at least two IAT procedures were eligible for the survey. Descriptive statistics were used to summarise results as well as inductive codification of open-ended questions.Results:The survey was answered by 200 individuals diagnosed with rheumatoid arthritis (66%), osteoarthritis (21%), spondyloarthritis (10%), psoriatic arthritis (9%), and others (16%). The mean number of IATs received was 7 (SD 8), mainly in the knee (66%), shoulder (42%), and wrist (28%), and primarily with corticosteroids (83%) or hyaluronic acid (16%). Twenty-seven percent had not been informed about benefits or potential complications of IAT, and 73% had not been asked whether they wanted local anaesthetic. Consent was deemed necessary by 82 (41%). Most (65%) had never received an ultrasound (US)-guided injection, and of those who had experienced blinded and guided injections, 42 (63%) preferred US-guided because of increased perceived accuracy and confidence in the procedure. Only 50% reported a clear benefit of IAT, mainly in terms of reduced pain and increased joint mobility, but also perceived reduced inflammation, with effect from immediate to 36 hours or even 3 weeks post-injection, and that lasted from as little as less than one week to years. Regarding safety, 40 (20%) had experienced some complications from IAT, including but not limited to increased pain, impaired mobility, rashes, or swelling.Finally, the respondents suggested improvements in the procedure, including: (1) wider availability; (2) less painful procedures; (3) greater efficacy, faster and longer-lasting; (4) fewer side effects; (5) a clear diagnosis beforehand; (6) better shared decision-making, including better information; (7) follow-up, (8) better accuracy; and (9) more expertise.Conclusion:The survey has identified gaps in the IAT procedures, such as a need for clearer information. Patients perceive IAT as relatively safe, though painful, and with varying effect. Suggestions for improving the procedure, including more expertise, should be relayed to professionals and relevant organisations.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:IRENE Pitsillidou: None declared, Jenny de la Torre-Aboki: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Abatacept (ABA) is a selective T-cell co-stimulatory modulator. After its approval, changes in therapeutic recommendations, the arrival of new drugs (e.g., biosimilars or Janus kinase inhibitors) and growing focus on comprehensive patient care may have changed prescription patterns, channeling ABA use towards specific patient subtypes. To date, studies analyzing these aspects in clinical practice settings are scarce.Objectives:We aimed to evaluate the epidemiological profile of ABA users and compare it to other DMARD groups included in the register.Methods:We performed an observational study based on the nationwide Spanish register BIOBADASER, which includes patients with rheumatic diseases receiving biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) from 28 tertiary centers. For this analysis, all RA patients included from December 2015 to December 2020 were examined. Baseline features were analyzed descriptively grouping all b/tsDMARDs by mode of action. Clinical effectiveness was assessed through drug survival obtained by the Kaplan-Meier method. Patients were right-censored if data were not available if they were still on treatment at the time of data analysis. The safety profile was assessed by the adverse events (AE) and serious AE incidence rates (IR) expressed as events per 1000 patient-years.Results:There were 628 ABA-treated patients, 471 (75%) using the subcutaneous presentation. Only 142 (23%) were on first-line while 381 (61%) were on third or later-line therapy. ABA users were older and more likely to present certain comorbidities compared to the other b/tsDMARD groups. The biggest relative differences were seen for interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), diabetes and ischemic heart disease. (Table 1)Table 1.This 12-month interim analysis includes 496 patients (336 with axSpA, 98 with RA and 62 with PsA)NABAIL-6CD20JAKiTNFi6287861816691787Mean age, years (SD)64.1 (12.0)50.7 (12.7)63.2 (12.3)59.6 (12.3)60.7 (13.1)Female sex, n (%)482 (77)652 (83)135 (75)537 (80)1418 (79)Median disease duration (p25-p75)10.1 (5.1-16.5)9.4 (4.6-15.9)13.3 (8.3-20.6)10.4 (5.0-17.2)7.4 (3.2-13.7)ACPA, n (%)352 (72)425 (71)113 (79)407 (70)875 (70)RF, n (%)380 (77)454 (75)124 (86)411 (70)915 (72)Current smokers, n (%)98 (16)137 (17)338 (19)90 (20)259 (18)ILD, n (%)64 (13)21 (3)25 (2)8 (2)19 (2)COPD, n (%)38 (6)23(3)52 (3)14 (3)43 (3)Chronic Kidney Disease, n (%)18 (3)13 (2)19 (1)13 (3)18 (1)Diabetes73 (12)66 (8)13 (7)46 (10)100 (7)Ischemic Heart Disease, n (%)36 (6)23 (3)012 (3)30 (2)Hypertension, n (%)197 (31)198 (25)416 (23)131 (30)338 (23)Heart Failure, n (%)19 (4)12 (2)10 (1)6 (2)5 (1)Osteoporosis, n (%)133 (21)141 (18)26 (14)72 (16)215 (15)IL-6: Tocilizumab and Sarilumab; CD20: Rituximab and biosimilars; JAKi: Janus kinase inhibitors (Tofacitinib and Baricitinib); TNFi: TNF inhibitors and biosimilars; ACPA: anti-citrullinated peptide antibodies; RF: rheumatoid factor; ILD: interstitial lung disease; COPD: chronic obstructive pulmonary disease.Overall, 63% of patients remained on ABA at 1 year, 48% at 2 and 31% at 5 years after drug initiation. The corresponding proportions were 79%, 65% and 52% for bionaïve and 59%, 43% and 30% for those in third or later-line therapy. From 394 total discontinuations, loss of efficacy in 225 (57%) and AE in 98 (25%) were the main reasons. This trend was consistent among all therapy lines.The total IR of AE was 886.5 (837.3-938.5) and 156.4 (136.5-179.2) for SAE. Infections were the most frequent AE overall, IR 44.4 (34.4-57.3), and the highest IR was seen among bionaïve patients (69.6 (44.9-107.9)).Conclusion:ABA-treated RA patients in Spain are older and have more comorbidities (vs other b/tsDMARDs), especially ILD, COPD, ischemic heart disease and diabetes and receive ABA as third or later-line therapy. Although these features are associated with worse response to treatment and a higher risk of infection, ABA presents a good drug survival and infectious AE are not the main cause of discontinuation.Acknowledgements:On behalf of the BIOBADASER Working groupDisclosure of Interests:Sebastián C Rodriguez-García Speakers bureau: Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Janssen, Consultant of: Bristol-Myers-Squibb, Galápagos, Carlos Sánchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Roche, Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Lilly, and Pfizer., Dolores Ruiz-Montesinos: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Juan J. Gómez-Reino Consultant of: Pfizer, Grant/research support from: Abbvie, Lilly, MSD, Pfizer, Roche, and UCB.

Background:Rheumatoid Arthritis (RA) is characterized by persistent joint synovitis causing progressive destruction of the cartilage and bone. Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA. Clinical profiles of patients with RA-associated ILD may vary.Objectives:To describe the clinical characteristics and radiological patterns and evaluate the different clinical profile between two different cohorts of patients (pts) with RA- associated ILD.Methods:Retrospective cohort study. We collected clinical and epidemiological data of pts seen in outpatient clinic from a Hospital from Barcelona, Spain and another from Jacksonville, Florida, USA. Pts who met the RA ACR/EULAR 2010 criteria and the ILD American Thoracic Society /European Respiratory Society 2013 classification criteria were selected. The study was approved by both local committees.Results:A total of 63 pts were included, 37 from Barcelona and 26 from Jacksonville. Forty-one pts (65%) were women with a median age of 68 years. General characteristics are summarized in Table. Thirty-eight pts (60.3%) were former smokers, but only 9 pts (14.3%) were current smokers. Fifty-two pts (82.5%) were Caucasian, 9.5% Mestizo, 3.2% Maghreb and 1.6% Indian. Most were overweight with mean BMI of 28.6 (SD 5.4). The Barcelona cohort showed more erosive disease than the pts from Jacksonville (26 vs 5 pts, p= 0.00). Seven pts had ILD diagnosis before RA. 4.82 (range 0-33) years was the median evolution from RA diagnosis until ILD diagnosis. Most common type of ILD was usual interstitial pneumonia (UIP) in 40% of pts, followed by nonspecific interstitial pneumonia (NSIP) in 25% of pts. Respiratory bronchiolitis was significantly more common in Barcelona cohort, while unspecific pattern in Jacksonville cohort (Table). A total of 71.4% were under GC treatment, methotrexate was used in 23 pts (36.5%), leflunomide in 14 (22.2%) and hydroxychloroquine in 7 pts (11.1%) prior to diagnosis of ILD. 6 out of 26 pts from Jacksonville were under MMF. TNF-α inhibitors were the most commonly used bDMARD in both cohorts as a first-line option prior to ILD diagnosis. Currently, half of the patients (50.8%) were under bDMARD. Current use of bDMARD was more often in US cohort (80.7%) than in Barcelona cohort (29.7%). Rituximab (RTX) was the most common bDMARD currently used (17 pts). Jacksonville pts were more commonly treated with RTX, while Barcelona pts were more commonly treated with Abatacept.Conclusion:Globally pts with RA-associated ILD have similar clinical profile in both centers, however, we found some differences in radiological patterns and treatment strategies between both cohorts. Those differences could be explained in part by sociodemographic differences, diagnostic and therapeutic approach and/or access for health care among others.Totaln=63 %Barcelona cohortn= 37Jacksonvillecohortn=26P valueCaucasian, patients (%)52 (82.5%)31 (83.8)21 (77.8)0,49Time RA evolution, mean years (SD)10.58 (8.01)11.63 (7)9 (9.24)0.80Time ILD evolution, mean years (SD)3.89 (3.20)3.86(3.28)4 (3.12)0.28Erosive disease, patients (%)31 (49.2)26 (72,2)5 (18.5)0,00Rheumatoid nodules, patients (%)8 (12,7)7 (18,9)1 (3.8)0,12Current scDMARDs treatment, patients (%)35 (55.55)31 (49.20)4 (6.34)0,002Current bDMARD treatment, patients (%)32 (50.8%)11 (17.5)21 (33.3)0,001ILD typeUsual interstitial pneumonia (UIP), patients (%)25 (40.3)14 (37.8)11 (44)0,08Nonspecific interstitial pneumonia (NSIP), patients (%)16 (25.8)14 (37.8)2 (8)0,23Respiratory bronchiolitis–interstitial lung disease (RB), patients (%)7 (11.3)7 (18.9)00,039Cryptogenic organizing pneumonia (OP), patients (%)4 (6.5)2 (5.4)2 (8)0,43Unspecific, patients (%)8 (12.9)08 (32)0,004Disclosure of Interests:Ana Belén Azuaga-Piñango: None declared, Yan Li: None declared, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Isabel Mira-Avendano: None declared, Andy Abril: None declared, Jose A. Gómez-Puerta Speakers bureau: Abbvie, BMS, GSK, Lilly, Pfizer, Roche

Background:In recent years, diverse compounds for intra-articular administration were brought into the market with a subsequent significant and heterogeneous literature production. Understanding the efficacy of intra-articular therapies (IAT) on pain implies bearing in mind the related placebo (PBO) effect. To date, most studies analyzing it were focused on the compound being administered rather than the route of administration.Objectives:We aimed at evaluating the size of the PBO effect after intra-articular injections.Methods:We conducted an overview of systematic reviews (SRs) including randomized-controlled trials (RCTs) of frequently used IAT. SRs with a saline solution PBO arm and high-confidence results according to the AMSTAR-2 tool were selected for analysis.Data on the change in pain in the PBO arms from baseline to 3-6 and 12-16 weeks after the IA procedure was extracted. The standardized mean differences (SMD) from baseline were calculated as the ratio between the size of the intervention effect in each study and the variability observed in that study. A meta-analysis was then performed using an inverse-variance random-effects model in Review Manager 5.3. The overall effect sizes obtained refer to versions of the SMD, which corresponds to the Hedges’ (adjusted) g. e.g. a “g” of 1 indicates the two groups being compared differ by 1 standard deviation and so on.Results:Two SR were included comprising 50 RCTs, 44 not meeting inclusion criteria were excluded so pain, measured by visual analogue scale (VAS) and Lequesne index, was retrieved from 6 RCT.At 3-6 weeks, an SMD [95%CI] = 0.74 [0.47-1.00] was found. One study showing too large an effect was excluded after conducting sensitivity analysis resulting in a significant reduction of heterogeneity with an SMD = 0.62 [0.45-0.79] (Fig.1). At 12-16 weeks, we found a SMD = 0.33 [0.13-0.52] (Fig.2)Figure 1.Forest plot for intra-articular PBO effect at 3-6 weeks after injection.Figure 2.Forest plot for intra-articular PBO effect at 12-16 weeks after injection.Using the interpretation suggested by Cohen1, our results would confirm a moderate to large effect of IA saline (PBO) at 3-6 weeks with a subsequent reduction to a small but persistent effect at 12-16 weeks.Conclusion:Our results showed a moderate to large short-term effect of intra-articular PBO that persisted on the mid-term although reduced. Based on these findings we suggest this effect should be considered when assessing the efficacy of IAT in RCTs and also in clinical practice where it could be maximized as well.References:[1]Cohen J. Statistical Power Analysis in the Behavioural Sciences (2nd edition). Hillsdale (NJ): Lawrence Erlbaum Associates, Inc., 1988.Disclosure of Interests: :Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Incidence of clinical fractures in rheumatoid arthritis (RA) is not as well-known as hip or vertebral fracture incidence.Objectives:1. To estimate the incidence of clinical fragility fractures in a population of postmenopausal women diagnosed with RA and compare it with that of the general population; 2. To analyze the risk factors for fracture.Methods:330 postmenopausal women with RA from 19 Spanish Rheumatology Departments, randomly selected from the registry of RA patients in each center. The control group consisted of 660 Spanish postmenopausal women from the Camargo Cohort. Clinical fractures during the previous 5 years were recorded. Assessed risk factors for fracture were: sociodemographic characteristics, BMD and variables related to RA.Results:Median age of RA patients was 64 yrs. vs. 63 yrs. in controls (ns). Evolution of the disease was 8 yrs. 78% and 76% had RF and ACPA+, respectively. 69% of patients were in remission or low activity. 85% had received glucocorticoids and methotrexate and 40% at least one biological DMARD. We identified 105 fractures (87 fragility and 18 traumatic) in 75 patients. Fifty-four patients and 47 controls had at least one major fracture (MF) (p< 0.001). Incidence of MF was 3.55 per 100 patient-year in patients and 0.72 in controls. Risk factors for MF in RA patients were age, previous fracture, parental hip fracture, postmenopausal period, hip BMD and cumulative dose of glucocorticoids. In controls, risk factors were age, age at menopause and lumbar BMD.Among RA-associated factors, MFs were associated with erosions, disease activity and disability. Previous fracture in RA patients was a strong risk for MF (HR: 10.37 [95% CI: 2.95-36.41]).Conclusion:Between 3 and 4 of every 100 postmenopausal women with RA have a major fracture per year, four times more than the general population. Disease activity and disability associated with RA, the cumulative dose of glucocorticoids and mainly previous fracture are associated with the development of fragility fractures.References:NoneAcknowledgments:Funded in part by ISCIII (PI18/00762) that included FEDER funds from the EU.Disclosure of Interests:Carmen Gómez Vaquero: None declared, Jose Manuel Olmos: None declared, J. Luis Hernández: None declared, Dacia Cerda: None declared, Cristina Hidalgo: None declared, JA Martínez López: None declared, Luis Marcelino Arboleya Rodríguez: None declared, Javier Aguilar del Rey: None declared, Silvia Martinez Pardo: None declared, Inmaculada Ros: None declared, Xavier Surís: None declared, Dolors Grados Canovas: None declared, Chesús Beltrán Audera: None declared, Evelyn Suero-Rosario: None declared, Inmaculada Gómez Gracia: None declared, Asunción Salmoral: None declared, Irene Martín-Esteve: None declared, Helena Florez: None declared, Antonio Naranjo Grant/research support from: amgen, Consultant of: UCB, Speakers bureau: AMGEN, Santos Castañeda: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, S García Carazo: None declared, Alberto García-Vadillo: None declared, Laura López Vives: None declared, À Martínez-Ferrer: None declared, Helena Borrell Paños: None declared, Pilar Aguado: None declared, Raul Castellanos-Moreira: None declared, Cristian Tebé: None declared, Núria Guañabens: None declared

Background:Intra-articular therapies (IAT) are widely used in clinical practice to treat patients with rheumatic and musculoskeletal diseases (RMDs). Many factors influence their efficacy and safety. There is a wide variation in the way IATs are delivered by health professionals. In an attempt to standardise these procedures, evidence-based recommendations are the right way forward.Objectives:To establish evidence-based recommendations to guide health professionals using IAT in adult patients with peripheral arthropathies.Methods:At a first face-to-face meeting, the results of an overview of systematic reviews were presented to the multidisciplinary task force of members from 8 countries. The aim, scope and outline of the taskforce were also established at this meeting. Thirty-two clinical questions ranked for priority (relevance for practice plus feasibility) drove the systematic reviews performed by two fellows. In addition, two surveys addressed to physicians, health professionals and patients throughout Europe were agreed to acquire more background information. At the second face-to-face meeting, the evidence for each research question was discussed, and each recommendation shaped and voted in a first Delphi round. Level of agreement was numerically scored 0 to 10 (0 completely disagree, 10 completely agree). All panellists voted anonymously using a sli.do app. Agreement needed to be greater than 80% to be included in a second Delphi round, which also allowed reformulation of statements. Finally, a third Delphi round was sent to the taskforce. The level of evidence was assigned to each recommendation according to the EULAR SOP for establishing recommendations.Results:Recommendations focus on practical aspects for daily practice to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles were established, together with 11 recommendations that address the following issues: (1) patient information; (2) procedure and setting; (3) accuracy issues; (3) routine and special antiseptic care; (4) safety issues and precautions to be addressed in special populations; (5) efficacy and safety of repeated joint injections; (6) the usage of local anaesthetics; and (7) aftercare. The document includes the supporting evidence and results from the surveys, level of evidence and agreement.Conclusion:We have developed the first evidence and expert opinion based recommendations to guide health professionals using IAT.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Terence O’Neill: None declared, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Ingrid Möller: None declared, Valentina Vardanyan: None declared, Jenny de la Torre-Aboki: None declared, Lene Terslev: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Elena Nikiphorou: None declared, IRENE Pitsillidou: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Intra-articular therapy (IAT) is subject to wide variability and there are gaps in the evidence on its efficacy and safety.Objectives:To assess the efficacy and safety of frequently used IATs to inform a EULAR Taskforce.Methods:We performed an overview of systematic reviews (SR) of randomised clinical trials (RCT) assessing efficacy and safety of IAT in adults with RMDs. MEDLINE was searched until January 2019. SRs were assessed with the AMSTAR-2 tool. Critically low-confidence SRs were excluded.Results:Of 159 articles identified, 42 were reviewed in detail and 15 met the inclusion criteria (146 RCTs). The populations included were mainly knee osteoarthritis (OA) in 10 SRs, rheumatoid arthritis (RA) in 3, hip and temporo-mandibular (TM) OA and shoulder adhesive capsulitis in 1 SR each.In knee OA, Hyaluronic Acid (HA) showed a modest benefit over placebo for pain and function but with unclear clinical significance in some studies. Platelet rich plasma (PRP) showed a small effect over HA only for function. Mesenchymal stem cells (MSC) performed better than PRP and HA for some outcomes, however, in studies with high risk of bias. Intra-articular Glucocorticoids (GC) were better than placebo (PBO) for pain and function.More adverse events (AE) were seen in the PRP group compared with HA and for HA compared with PBO including serious AE each in 1 SR on knee OA.Results for other included diseases are shown in table 1.Table 1.Summary of SR. P: population; C: comparation; H: High, M: Moderate; L: Low confidence; MA: meta-analysis; SOC: standard of care; PRO: patient reported outcomes; ROM: range of motion; MPA: methylprednisolone acetate; TA/TH: triamcinolone acetonide/ hexacetonide; MW: molecular weight; YR: Yttrium synoviorthesis *Same SR assessed knee arthritis in OA and RA separatelySRPCAMSTAR2EfficacySafetyNewberryknee OAHA vs PBO; HA; LavageHMA.HA better than PBOin function in older patients (small effect).No diff in AEJuniGC vs Sham; PBO; SOCHMA.GC betterin pain and function until 6w. No diff at 12-24w.No diff in AEPasMSC vs PBO; PRP; HAMNo MA.MSC betterin pain, PRO, MRI, etcHigh risk of bias.No diff in AETrojianHA vs PBO; GCMNMA.HA better vs GC or PBOin WOMAC pain, stiffness, function and OARSI criteria.No diff in AEGallagherHA vs PBOMNo MA.No diffin joint space width.High risk of bias.Not reportedSamsonHA vs Glucosamine; Chondroitin; LavageMMA.HA betterin pain (small effect), unclear clinical benefitMA. More AE with HA.SAE in 3/1002 knees with HA(severe swelling, hypersensitivity reaction)DiPRP vs HALNo MA.PRP betteronly in WOMAC function.More AE with PRP(pswelling)Silvinato*MPA vs TA; THLMA.MPA better vs TA in pain until w6No diff. in pain or function at 12w.No diff in AETrigkilidasHA vs PBO; GCLNo MA.HA (small effect) better in mild-moderate OANo diff in AELoHA vs PBOLNo MA.HA (small effect) better in pain. (publication bias).High heterogeneityNo diff in AEDe SouzaTM OAHA vs GCMHA better in pain at w24Not reportedFigueiredoHip OAHA vs GC; PBO; PRP; AnaestheticsLMA.No diffin HA vs comparators in pain and OARSI criteriaNo diff in AELeeShoulder capsulitisHA vs SOCMNo MA.No diffin HA vs SOC.No diff in AEHeuftRA (knee)YR vs PBO; GCMNo MA.YR better vs PBO, TH better vs YR in ROM and knee circumference.SR inconclusiveNot reportedSilvinato*MPA vs TA; THLMA.No diffin pain or function.No diff in AESaitoHA vs PBOLMA.HA better in global effectiveness, pain and inflammation.No diff in AEConclusion:Most of the SRs assessed had results of low confidence. HA and GC showed a small, short term benefit in knee arthritis in OA and RA compared to PBO. High risk of bias prevents conclusions on the efficacy of PRP and MSC in knee OA. More AE were reported in PRP and HA treated groups.Disclosure of Interests: :Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Respiratory tract infections are among the leading causes of hospitalization in rheumatoid arthritis (RA) and Streptococcus Pneumoniae (Sp) is one of the most frequent pathogens involved. For these patients, the CDC recommends a combined vaccination scheme (CVS) using two types of Sp vaccines but evidence on its effectiveness remains insufficient.1Objectives:To assess the impact of the combined vaccination scheme on the incidence of Sp infections in patients with RA treated with DMARD.Methods:A cohort was nested in a register including patients with RA who were prescribed a bDMARD or tsDMARD -either naïve or switch- from 2000 to March 2019.The target outcomes were invasive pneumococcal disease (IPD) and all-cause community-acquired pneumonia (CAP), as defined by relevant MedDRA codes. Demographic and clinical features were also retrieved. Each participant centre informed about the date when they implemented a systematic Sp vaccination protocol and whether they were using the CVS. Those not adopting this practice were excluded from the analysis.Crude incidence rates (IRs) were calculated for each outcome as well as for its combination (combined variable defined as “Sp infections”). Exposure was split into two periods, considering the date when the CVS was officially recommended in Spain (May 2015). The incidence rate ratio (IRR) comparing pre and post implementation periods was estimated with a Poisson regression model adjusted for sex, age and comorbidities (Charlson Index).Results:1704 patients were included, their characteristics are shown in table 1. One centre was excluded for not using any Sp vaccination protocol while the remaining ones reported using the CVS. Crude IRs by periods (pre and post CVS implementation) and age groups are shown in table 2. The IRR of the post-vaccination period after adjusting for age, sex and comorbidities (Charlson index) was 0.40 (95% CI: 0.29 - 0.56), pTable 1.Baseline features of the cohort.DemographicsAge, years *60.6 (12.5)Female1356 (79.6%)Current smoking287 (16.8%)RA clinical characteristicsDisease duration, years*9.1 (7.9)RF positive875 (74%)ACPA positive831 (71%)DAS28*4.6 (1.4)Other clinical characteristicsBody Mass Index*27.5 (5.2)Charlson index*2.3 (1.5)Chronic pulmonary Disease125 (9.3%)Diabetes mellitus147 (9%)*Data presented as mean (standard deviation).Table 1Characteristics of patients with RA at time of RA diagnosis and patients with SAB with/without RA at time of SAB diagnosisCharacteristic, n (%)At RA diagnosisAt first-time SABRA (n=34,627)RA (n=228)Non-RA (n=25,268)Age, years (IQR)59.8 (48.8-70.3)71.8 (62.3-79.2)69.7 (57.7-79.7)Female, %69%59%38%Diabetes mellitus2,467 (7.1%)51 (22.4%)5,678 (22.5%)Heart failure1,018 (2.9%)42 (18.4%)4,718 (18.7%)Liver disease454 (1.3%)12 (5.3%)2,189 (8.7%)Chronic obstructive pulmonary disease1,677 (4.8%)36 (15.8%)3,412 (13.5%)Cancer2,124 (6.1%)60 (26.3%)6,742 (26.7%)HIV11 (0.0%)0 (0%)127 (0.5%)Solid organ transplant8 (0.0%)0 (0%)357 (1.4%)Alcohol abuse642 (1.9%)12 (5.3%)3,356 (13.3%)Chronic dialysis29 (0.1%)11 (4.8%)2,256 (8.9%)Orthopedic implant3,807 (11.0%)89 (39.0%)5,422 (21.5%)Cardiac or vascular implant731 (2.1%)18 (7.9%)1,940 (7.7%)Glucocorticoid (0-90 days prior)7,062 (20.4%)99 (43.4 %)2,911 (11.5%)Invasive surgery (0-30 days prior)1,962 (5.7%)62 (27.2%)8,451 (33.5%)Table 2.Crude IRs (95% CI) of the outcomes of interest split by age.Overall≥65PrePostPrePostPrePostSP-Infections33 (27.4-39.9)12.7 (9.8-16.4)28 (22.4-35)11.8 (8.9-15.6)60.3 (42.4-85.8)19.5 (10.8-35.2)IPD–0.4 (0.1-1.6)–0.4 (0.1-1.8)––All cause CAP23.6 (19.0-29.3)11.5 (8.8-15)18.7 (14.4-24.4)10.4 (7.7-14)50.8 (34.8-74)19.5 (10.8-35.2)Conclusion:The incidence of Sp infections experienced a decrease in RA patients taking bDMARD or tsDMARD after the introduction of the stepwise combined vaccination scheme that is not related to age, sex or comorbidities.References:[1] Furer V,et al.Ann Rheum Dis2019;0:1–14Disclosure of Interests:Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Carlos Sánchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Dolores Ruiz-Montesinos: None declared, Victoria Hernandez: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), Juan Jesús Gómez-Reino: None declared

Background:Intra-articular therapies (IAT) are routinely used in rheumatic and musculoskeletal diseases (RMDs); however large variability exists regarding current practice of delivery amongst health professionals.Objectives:To inquire about common practice aspects to inform the EULAR Taskforce for the IAT of arthropathies.Methods:A steering committee prepared a 160-item questionnaire based on the information needs of the Taskforce. The survey was disseminated via EULAR professional associations and social media and it was open to any health professional treating persons with RMDs, regardless of using IAT personally.Results:The survey was answered by 186 health professionals from 26 countries, the large majority of whom (77%) were rheumatologists, followed by nurses (12%), general practitioners (2%) and orthopaedic surgeons (2%). The two collectives that perform IAT routinely are rheumatologists (97%) and orthopaedic surgeons (89%), with other professionals Conclusion:Although often performed in clinical practice for RMDs, there is apparent variability in several elements related to delivery of this treatment. This information, together with patient input, will help design current recommendations where research evidence is not available.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jenny de la Torre-Aboki: None declared, IRENE Pitsillidou: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Patients and Rheumatologist often differ in their perception of RA disease activity. Remission or low disease activity should be the treatment target in RA, patients should be included in treatment decisions.Objectives:To identify factors influencing patient’s self-reported disease activity by RAPID3 test.Methods:47 RA patients in remission or low disease activity by DAS28ESR (DAS28ESR ≤ 3.2) receiving TNFi (etanercept, adalimumab and infliximab) stratified their disease activity by RAPID3, then two patients’ groups were defined:target group(RAPID3 with remission 0-3 or low disease activity 3.1-6),non-target group(RAPID3 with moderate 6.1-12 or high disease activity >12). Demographic data, disease duration, autoantibody status, radiological data, concomitant csDMARD therapy was collected. Laboratory measurements included CRP, ESR, calprotectin serum levels, TNFi trough serum levels, and antidrug antibodies (enzyme-linked immunosorbent assay (ELISA) test kit (Calprolab™ Calpro AS, Oslo, Norway, and Promonitor®, Progenika SA, Spain, respectively) according to the manufacturers’ protocol. Pearson´s correlations coefficients were used to identify variables correlating with RAPID3 score. Mixed-effects analyses of covariance (ANCOVAs) models were used to identify factors influencing RAPID3 score.Results:Patients in “target group”have shown a significant lower TJC, pain by VAS 0-10mm, and calprotectin serum levels, but higher TNFi serum trough levels in comparison to “non-target group”. When patients were classified according to RAPID 3 categories, patients in “remission” have shown lower calprotectin serum levels than those classified as in “high disease activity” (0.94 (4.88-0.14) vs. 4.57 (7.97-1.25),p=0.001, respectively). Accordingly, when classified according to pain by VAS 0-10mm, patients with low levels of pain had lower calprotectin serum levels vs. those with severe pain (1.43 (6.33-10.14) vs. 5.16 (8.80-1.25),p=0.009, respectively). When distributed according to PGA (1=very good, 2=good, 3=regular, 4=bad, 5=very bad) patients in “very good” group had lower mean of calprotectin serum levels than those in “very bad” group (0.94 (4.88-0.14) vs. 4.57 (7.97-1.25),p=0.001, respectively). PGA and Pain VAS have shown a strong correlation with RAPID 3 (R20.978, and 0.834,p=0.001, respectively), while calprotectin and TNFi serum trough levels showed a moderate correlation (R20.311, and 0.372,p=0.005, respectively). The multivariate adjusted analysis showed a significant association between Pain and RAPID3 (pConclusion:61.7% of RA patients undergoing TNFi classified as in remission or low disease activity by DAS28ESR, self-reported their disease activity as moderate or high by RAPID3. The most significant factor influencing patient’s perception of disease activity is pain (pain VAS and TJC). However, inflammation markers (calprotectin, TNFi serum trough levels) remain statistically significant after fully adjustment by different confounders. Thus, therapies improving these three domains will have a larger impact in patient´s perception of disease activity.References:[1]Studenic P, et al. Arthritis Rheum. 2012;64:2814-23.Disclosure of Interests:Jose Inciarte-Mundo Employee of: Eli Lilly, Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Rosa Morlà Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Beatriz Frade-Sosa: None declared, Julio Ramírez Speakers bureau: Abbvie, Eli Lilly, BMS, Roche, Novartis and Pfizer, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Juan de Dios Cañete: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer

Background:Interstitial lung disease (ILD) is associated with a significant increase in morbidity and mortality in patients with rheumatoid arthritis (RA). Therefore, an early diagnosis is fundamental. Anti-carbamylated proteins (Anti-CarP) have been described in different chronic respiratory diseases without a previous history of RA.Objectives:The aim of this study was to analyse the association between Anti-CarP and ILD in RA patients.Methods:We performed a cross-sectional study, including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised 2 groups: 1) RA patients diagnosed with ILD (RA-ILD group) and 2) RA patients without ILD (non-ILD RA group). ILD was diagnosed by high-resolution tomography and confirmed by a multidisciplinary committee. Three IgG Anti-CarP autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib), and fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarPs and ILD were explored using multivariable logistic regression adjusted by a set of variables known to be related to the development of ILD: smoking, sex, age, RA disease duration, RF and ACPA. An independent replication sample was obtained to validate our findings from another hospital.Results:The main population included 179 patients: 37 were included in the RA-ILD group, and 142 in the non-ILD RA group. Most patients were female (79%), with a mean age of 59.7±13 years with a mean disease duration of 6.6±5 years. Baseline features are shown in table 1. The replication sample was composed of 25 patients in the RA-ILD group and 50 patients in the non-ILD RA group. We found that Anti-CarPs specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs. 43%; Anti-Fib 73% vs. 51%; Anti-CFFHP 38% vs. 19%; Anti-CarP-IgA 51% vs. 20%, pTABLE 1.Main population demographic, clinical, therapeutic, and autoantibody status features.RA-ILDn:37Non-ILD RAn:142p valueFemale (%)25 (68)116 (82)NSAge mean (±SD)67.3 (10.1)57.7 (12.9)Mean disease duration (±SD)11.6 (7.1)5.3 (13.3)Ever smokers (%)21 (57)62 (44)NSSmoking cumulative dose (±SD)30.7 (11.1)21.8 (12)Caucasian (%)31 (84)120 (85)NSTreatmentGlucocorticoids (%)25 (68)81 (57)NScsDMARDs (%)33 (89)132 (86)NSMTX (%)20 (54)95 (67)NSbDMARDs (%)11 (30)36 (25)NSMean DAS28 (±SD)3.71 (1.35)2.74 (1.05)Erosive disease (%)26 (70)63 (44)Mean HAQ-DI (CI-95%)0.69 (0.53-0.85)0.31 (0.24-0.38)ACPA positive (%)29 (78)99 (70)NSMedian titer ACPA (IQR) CU674 (2,215)143 (1,132)NSRF positive (%)28 (76)83 (59)NSMedian titer RF (IQR) IU105 (298)34 (110)NSConclusion:A strong association between RA-ILD and Anti-CarP was found independently of cofounders, including RF and ACPA. Our findings suggest a possible link between Anti-CarP and the development of ILD.Disclosure of Interests:Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Sebastian Rodriguez-Garcia: None declared, Katherine Cajiao: None declared, Gabriela Jimenez: None declared, Maria Jose Gomara: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Ivette Casafont-Solé: None declared, Julio Ramirez: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Susana Holgado Pérez: None declared, Juan de Dios Cañete: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer

We welcome the comments by Alunno et al on our article about the association between anticarbamylated protein antibody (anti-CarP) specificities and rheumatoid arthritis-associated interstitial lung disease (RA-ILD).1 The authors proposed a ‘mix and match approach’ consisting of the assessment of various antibody specificities at RA diagnosis with the aim of predicting the development of ILD.2 We believe this hypothesis is reasonable, considering that different antimodified protein antibodies (AMPA) including anti-CarP, anticitrullinated and antiacetylated protein antibodies (ACPA and anti-AceP, respectively) have been associated with RA-ILD.1 3 4 Furthermore, a …

We read the article by Mankia et al on the distinct ultrasound (US) imaging phenotype in palindromic rheumatism (PR) with great interest.1 The authors found characteristic US findings in PR during flares that differ from those observed in patients with early rheumatoid arthritis (RA) or anti-cyclic citrullinated peptide (CCP)+ arthralgia. US extracapsular inflammation (periarticular inflammation, subcutaneous or peritendinous oedema), in most cases without joint synovitis, is the most frequent US finding in PR. These findings disappeared after acute attacks. The authors concluded that this imaging phenotype of extracapsular inflammation is specific for PR and may be distinguished from that observed in RA or persistent arthritis. They also suggest that true US intrasynovial inflammation may predict future RA in these patients. …