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Background To investigate the frequency of difficult-to-treat (D2T) rheumatoid arthritis (RA) in patients early escalated to biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) after failure of treat-to-target with methotrexate (MTX). Methods From a prospective cohort of early RA, all patients with their first access in the years 2005–2018, and eventually starting a b/tsDMARD before the end of 2022, were included and followed-up until April 2024. Study outcomes included drug survival on each consecutive b/tsDMARDs, development of D2T (according to the EULAR definition and subsequent modifications), and its predictors. Results Of a total cohort of 722 early RA patients treated with initial MTX and followed-up for at least 3 years from diagnosis, 155 (21.5%) had started a b/tsDMARD after a median of 19 months. In more than 70% of the cases, RA was uncontrolled despite optimal doses of MTX of ≥ 15 mg/day. The retention rates of the first and the second b/tsDMARD were approximatively 70% after 1 year but dropped to 40% after 5 years. After a median (IQR) follow up of 72.6 (34.5-134.2) months, 45 patients (29%) fulfilled the EULAR D2T criteria. At multivariable analysis, higher number of swollen joints and worse pain scores were confirmed as predictors of D2T. Furthermore, in this early RA cohort, shorter disease duration at the start of treatment with b/tsDMARDs, together with negativity for autoantibodies, were also independent predictors of D2T. Conclusions Early implementation of treatment after failure of treat-to-target with MTX may not prevent the development of D2T in RA. Patients showing early refractoriness to conventional drugs and those lacking autoantibodies are at higher risk of multiple treatment failures.

Background: Major improvements in the management of rheumatoid arthritis (RA) have made clinical remission an achievable and desirable goal but, despite the relevance gained by a profound disease suppression, many patients with RA still miss clinical remission due to several factors influencing disease activity, including treatment adherence. Objective: To evaluate the effect of adherence to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on the achievement of clinical remission in a cohort of patients with new-onset inflammatory arthritis. Study design: A prospective cohort study was conducted using the ELECTRA database, which consists of clinical data from patients followed at the IRCCS Policlinico San Matteo Foundation (Pavia, Italy), linked to regional administrative healthcare databases. Methods: We enrolled patients with new-onset active disease between January 2006 and December 2013 and followed them until their first clinical remission or end of follow-up (December 2015). To assess the association of csDMARD adherence with clinical remission, we estimated the csDMARD proportion of days covered (PDC) during follow-up. PDC was added to the main clinical adjustment covariates as a time-dependent variable in a proportional hazard Cox regression model. Results: The cohort included 324 patients with a mean (SD) age of 58 (13.9) and predominantly female (74.5%). A total of 219 patients (67.6%) achieved clinical remission during follow-up and 85 (26.2%) in the first 6 months (early clinical remission). Cox regression models showed that a 10% increment of PDC increased the probability of achieving clinical remission by 10% (p < 0.001) and the probability of early clinical remission by 21% (p = 0.03). Conclusion: Patients at disease onset with higher adherence to csDMARDs were more likely to achieve clinical remission and early clinical remission. Our study highlighted the importance of close monitoring of patients to increase their likelihood of following therapeutic indications and achieving favorable disease outcomes, such as lower disability.

Background While low-dose oral glucocorticoids (GCs) are recommended in the management of early arthritis, their impact on mortality is unclear. The aim of this study is to evaluate the effect of GCs on mortality in patients with early arthritis, by linking clinical and administrative databases. Methods The study included patients with new-onset rheumatoid arthritis (RA) or undifferentiated arthritis (2005–2010), who received DMARDs (MTX in RA or UA with poor prognosis, hydroxychloroquine in UA) and were alive at the second year of follow-up. Low-dose GCs could be prescribed. Clinical and administrative data were linked from Administrative Health Databases (AHD) of the corresponding province, which provided us with information on drug delivery, comorbidities, hospitalization, and mortality. The effect of GCs in the first year was defined using a dichotomous variable or a 3-level categorization (not delivered, ≤7.5 mg/day, or >7.5 mg/day of prednisone) on all-cause mortality, assessed with Cox regression, either crude or adjusted for age, gender, Charlson Comorbidity Index (CCI) or single comorbidities, ACPA, HAQ, and MTX in the first year. A secondary analysis of the effect of GCs on related hospitalizations (for cardiovascular events, diabetes, serious infections, osteoporotic fractures) was also carried. Results Four hundred forty-nine patients were enrolled (mean age 58.59, RA 65.03%) of which 51 (11.36%) died during the study. The median (IQR) follow-up was equal to 103.91 (88.03–126.71) months. Treatments with GCs were formally prescribed to 198 patients (44.10%) at ≤7.5 mg/day, although by the end of the study such treatments were received by 257 patients (57.24%); 88 patients (19.6%) were treated with GCs at >7.5 mg/day. In adjusted analyses, the GC delivery (HR, 95% CI 1.35 (0.74, 2.47)) did not significantly predict mortality — both at a low (HR, 95% CI 1.41 (0.73, 2.71)) and at a high (HR, 95% CI 1.23 (0.52, 2.92)) dosage. When “all-cause hospitalization” was used as an outcome, the analysis did not show a difference between patients receiving GC and patients not receiving GC. Conclusion In patients with early inflammatory arthritis, the initial GC dose was higher than that prescribed by rheumatologists; however, on background treatment with DMARDs, GC treatments did not seem to increase mortality and hospitalizations.

To explore the influence of comorbidities on clinical outcomes and disease activity in rheumatoid arthritis (RA). In patients included in the cross-sectional observational multicenter international study COMORA, demographics, disease characteristics and comorbidities (hypertension, diabetes, hyperlipidemia, renal failure, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity) were collected. Multivariable linear regression models explored the relationship between each comorbidity and disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient's and physician's global assessment (PtGA, PhGA), patient reported fatigue and 28-Disease Activity Score (DAS28). Results are expressed as mean difference (MD) adjusted for the main confounders (age, gender, disease characteristics and treatment). A total of 3,920 patients were included: age (mean ±SD) 56.27 ±13.03 yrs, female 81.65%, disease duration median 7.08 yrs (IQR 2.97-13.27), DAS28 (mean ±SD) 3.74 ± 1.55. Patients with diabetes had more swollen and tender joints and worse PtGA and PhGA (MD +1.06, +0.93, +0.53 and +0.54, respectively). Patients with hyperlipidemia had a lower number of swollen and tender joints, lower ESR and better PtGA and PhGA (MD -0.77, -0.56, -3.56, -0.31 and -0.35, respectively). Patients with history of ischemic heart disease and obese patients had more tender joints (MD +1.27 and +1.07) and higher ESR levels (MD +5.64 and +5.20). DAS28 is influenced exclusively by cardiovascular comorbidities, in particular diabetes, hyperlipidemia, ischemic heart disease and obesity. Cardiovascular comorbidities relate more than others with disease activity in RA. Diabetes and hyperlipidemia in particular seem associated with higher and lower disease activity respectively influencing almost all considered outcomes, suggesting a special importance of this pattern of comorbidities in disease activity assessment and clinical management.

Background: The patient global assessment of disease activity (PGA) is the major limiting factor to Boolean remission in patients with established rheumatoid arthritis (RA). Here, we investigated the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs, also in relation to autoantibody status. Methods: Data were retrieved from 535 early RA patients (<12 months of symptoms) with an observation period of 6–12 months upon initiation of therapy with methotrexate aimed at the achievement of low disease activity based on the 28-joints disease activity score. Near-remission was defined as any of the four core items of Boolean remission >1 with the remaining three all ⩽1. Reasons for missing Boolean remission and predictors of near-remission subcategories were analyzed in relation to baseline disease variables. Results: After 6 and 12 months, near-remission was two-times more frequent than Boolean remission (25.6% and 26.9% at the two time-points). A 28-swollen joint count (SJC28) >1 was responsible for the majority of near-remission (56.2% and 57.6% at 6 and 12 months, respectively), and PGA > 1 accounted for approximatively 35% of the cases. Autoantibody-positivity independently predicted the risk of missing remission because of SJC28 > 1 [adjusted odds ratio (OR) 95% confidence interval (CI) 2.81 (1.59–4.9) at 6 months and 1.73 (1.01–3.01) at 12 months], whilst autoantibody-negativity was an independent predictor of PGA near-remission [adjusted OR (95% CI) 2.45 (1.25–4.80) at 6 months and 5.71 (2.47–13.2) at 12 months]. Conclusion: In early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst PGA more frequently impairs remission in autoantibody-negative patients. Efforts to target full-remission in early RA may thus require different strategies according to autoantibody profile.

Objective. To develop and test an algorithm with the aim of optimizing the implementation of ultrasound in the diagnostic workflow in clinical practice. Methods. Through a consensus among the Musculoskeletal Ultrasound (MSUS) Study Group of the Italian Society for Rheumatology, we identified clinical and laboratory variables to be included in 1000minds surveys to develop an algorithm driving clinical diagnostic suspicion. The algorithm would identify potential differential diagnoses where MSUS protocols targeted for specific diseases (rheumatoid arthritis, psoriatic arthritis, gout, calcium pyrophosphate deposition disease, polymyalgia rheumatica, and osteoarthritis) could be applied. The joint sites and elementary lesions for each disease were selected based on a previously performed systematic literature review (SLR) and consensus. Finally, we conducted a pilot study on patients with new-onset arthritis to assess the performance of the algorithm, comparing the algorithm-based diagnosis with the final clinical diagnosis. Results. Based on the consensus and the surveys, age, the number of involved joints, anti-citrullinated protein antibody, rheumatoid factor, C-reactive protein, and erythrocyte sedimentation rate were included in the algorithm. The pilot study included 59 patients: median (interquartile range) age 62.2 (54.1-72.6) years, 78% female. The agreement between the diagnosis selected by the algorithm and the final diagnosis by the rheumatologist was 88.1%. The elementary lesions and joint sites included in the different MSUS protocols were selected based on the best diagnostic accuracy, as shown by the SLR and defined by the working group. Conclusions. The developed algorithm was accurate in identifying the correct diagnosis. Thus, it could reliably drive the decision on the MSUS assessment to perform. The RADIAL study will further investigate the feasibility and added value of MSUS in the diagnostic workflow according to this newly developed clinical suspicion-driven algorithm.

Recent advancements in the management of inflammatory arthritis have shifted the focus toward patient-centered care, with increasing emphasis on patient education, engagement, and treatment adherence. At the same time, the growing use of imaging techniques offers novel opportunities to enhance communication between healthcare professionals and patients. This review examines current evidence on how visual tools and imaging modalities can improve patient understanding, foster engagement, and strengthen adherence in inflammatory arthritis. Barriers to adherence often arise from low health literacy and entrenched beliefs about illness and medications. However, visual communication has shown promise in addressing these challenges. Research in rheumatoid arthritis (RA), juvenile idiopathic arthritis, and gout suggest that showing personal or illustrative images can increase disease insight, reinforce treatment necessity, and encourage shared decision-making. Among imaging techniques, musculoskeletal ultrasound (MSUS) stands out for its real-time use and interactive potential. Although findings—especially in RA—are encouraging, the overall evidence remains limited, with lack of research in spondyloarthritis and scarce data on long-term outcomes. Further studies are needed to develop standardized protocols and identify patient subgroups most likely to benefit. Ultimately, integrating imaging into patient education may be a valuable strategy to improve care experiences and outcomes in inflammatory arthritis.

With the rapid expansion of artificial intelligence (AI) applications, researchers have begun focusing on the concept of human-centered artificial intelligence (HCAI). This field is dedicated to designing AI systems that augment and improve human abilities, rather than substituting them. The objective of the paper was to review the information on design principles, techniques, applications, methods, and outcomes adopted in the field of HCAI, in order to provide some insights on the discipline, in relation with the broader concepts of human-centered and user-centered design. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist guidelines, we conducted a scoping review in PubMed, ScienceDirect, and IEEE Xplore, including all study types, excluding narrative reviews and editorials. Out of the 1035 studies retrieved, 14 studies conducted between 2018 and 2023 met the inclusion criteria. The main fields of application were the health sector and AI applications. Human-centered design methodologies were adopted in 3 studies, personas in 2 studies, while the remaining methodologies were adopted in individual studies. HCAI emphasizes designing AI systems that prioritize human needs, satisfaction, and trustworthiness, but current principles and guidelines are often vague and difficult to implement. The review highlights the importance of involving users early in the development process to enhance trust, especially in fields like health care, but notes that there is a lack of standardized HCAI methodologies and limited practical applications adhering to these principles.