Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews.

OBJECTIVE: To summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations. METHODS: An overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool. RESULTS: Of 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences. CONCLUSIONS: This overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found.

EULAR recommendations for intra-articular therapies.

OBJECTIVES: To establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies. METHODS: A 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. RESULTS: Recommendations 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. CONCLUSION: We 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.

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease.

OBJECTIVE: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies. RESULTS: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP 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%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample. CONCLUSIONS: Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.