Novel insights into the management of rheumatoid arthritis: one year in review 2024.

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data.Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Systematic literature review to inform the EULAR recommendations for the use of imaging in crystal-induced arthropathies in clinical practice.

OBJECTIVE: To summarise current data regarding the use of imaging in crystal-induced arthropathies (CiAs) informing a European Alliance of Associations for Rheumatology task force. METHODS: We performed four systematic searches in Embase, Medline and Central on imaging for diagnosis, monitoring, prediction of disease severity/treatment response, guiding procedures and patient education in gout, calcium pyrophosphate dihydrate deposition (CPPD) and basic calcium phosphate deposition (BCPD). Records were screened, manuscripts reviewed and data of the included studies extracted. The risk of bias was assessed by validated instruments. RESULTS: For gout, 88 studies were included. Diagnostic studies reported good to excellent sensitivity and specificity of dual-energy CT (DECT) and ultrasound (US), high specificity and lower sensitivity for conventional radiographs (CR) and CT. Longitudinal studies demonstrated sensitivity to change with regard to crystal deposition by US and DECT and inflammation by US and structural progression by CR and CT. For CPPD, 50 studies were included. Diagnostic studies on CR and US showed high specificity and variable sensitivity. There was a single study on monitoring, while nine assessed the prediction in CPPD. For BCPD, 56 studies were included. There were two diagnostic studies, while monitoring by CR and US was assessed in 43 studies, showing a reduction in crystal deposition. A total of 12 studies with inconsistent results assessed the prediction of treatment response. The search on patient education retrieved two studies, suggesting a potential role of DECT. CONCLUSION: This SLR confirmed a relevant and increasing role of imaging in the field of CiAs.

2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice.

OBJECTIVE: To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). METHODS: An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. RESULTS: Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). CONCLUSIONS: These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

Effects of cytotoxic T-lymphocyte-associated protein 4 compared to TNF inhibitors on lipid profile: Results from an observational multicentre rheumatoid arthritis cohort.

AIM: To evaluate the impact of selective cytotoxic T-lymphocyte-associated protein 4 (CTLA-4Ig) compared to tumor necrosis factor inhibitors (TNFi) on cardiovascular (CV) clinical and laboratory outcomes in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational multicenter study of RA patients included in the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group database, collecting demographic, clinical, and laboratory data of those starting a CTLA-4Ig or TNFi at baseline, 6-month, and 12-month follow-up. RESULTS: Of the 206 RA patients without previous CV events enrolled in the study, 64 received a CTLA-4Ig and 142 a TNFi. The two groups did not differ in age, gender, or smoking habits, and the prevalence of hypertension, diabetes, and metabolic syndrome was similar. Over a follow-up period of 12 months, although no significant differences were found in the disease activity course, we observed that LDL cholesterol levels slightly decreased only in the CTLA-4Ig-treated patients. CONCLUSIONS: Patients treated with both CTLA-4Ig and TNFi did not differ in disease activity response and changes in traditional CV risk factors after 12 months of treatment. However, CTL-A-4Ig treatment is associated with a favorable change in lipid profile at 12-month follow-up.

Impact of csDMARDs adherence on clinical remission in patients with new-onset inflammatory arthritis: a prospective cohort study from the ELECTRA database.

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.

Novel insights into the management of rheumatoid arthritis: one year in review 2023.

New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Administrative Databases and Diagnostic Therapeutic and Assistance Paths -PDTA- in the Monitoring Treatment of Rheumatoid Arthritis: The Experience of ATS Pavia.

Background: The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions. Objective: The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area. Methods: Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR). Results: A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars. Conclusion: In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.

Italian recommendations for the assessment of cardiovascular risk in rheumatoid arthritis: a position paper of the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group of the Italian Society for Rheumatology.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events. The aim of this position paper is to provide Italian rheumatologists with an easy, feasible and time-saving CV risk assessment in their daily clinical practice. METHODS: A narrative review of the literature and an assessment of the methodological strength underlying the current evidence on CV risk assessment in patients with RA were performed. The evidence-based results were shared among the members of the steering committee of the CORDIS study group of the Italian Society of Rheumatology. Subsequently, a unanimously agreed-upon algorithm was discussed and finally approved by the experts. RESULTS: RA patients should have their CV profile monitored using the Italian 'Progetto Cuore' chart, according to the current EULAR recommendations for CV risk management, at least every 5 years. In the presence of high disease activity, or a multi-drug failure condition, when prolonged treatment with glucocorticoids and/or NSAIDs is required, or if hypertension, dyslipidaemia, or diabetes mellitus are concomitant, a more stringent CV risk assessment should be considered. When moderate CV risk is documented, patients should undergo intima-media thickening measurement. The condition of high CV risk requires a cardiological evaluation. CONCLUSIONS: This position paper provides five Italian recommendations for CV risk assessment in RA patients. A general and uniform approach to CV risk profiling may be useful to identify those patients who should undertake intensive preventive strategies to improve their CV outcomes.

Which are the most frequently involved peripheral joints in calcium pyrophosphate crystal deposition at imaging? A systematic literature review and meta-analysis by the OMERACT ultrasound - CPPD subgroup.

Objectives: To identify the prevalence of calcium pyrophosphate crystal deposition (CPPD) using ultrasound and conventional radiology at peripheral joints in patients with suspected or definite CPPD. Methods: A systematic literature search was performed in PubMed and Embase using pre-defined search strategies from inception to April 2021 to identify studies that evaluated conventional radiology and ultrasound in detecting CPPD at peripheral joints, including definite or suspected CPPD [Research question 1 (RQ1) and Research Question 2 (RQ2), respectively]. For the meta-analysis, the first, second, and third sub-analysis included studies with the knee, and knee or wrist as the index joint for CPPD (without restrictions on the reference standard) and synovial fluid analysis or histology as a reference standard (without restrictions on the index joint), respectively. Results: One-thousand eight hundred and twenty-seven manuscripts were identified, of which 94 articles were finally included. Twenty-two and seventy-two papers were included in RQ1 and RQ2, respectively. The knee had the highest prevalence for RQ1 and RQ2 by both conventional radiology and ultrasound, followed by the wrist with the highest prevalence for RQ1. The hand had the lowest CPPD prevalence. The third sub-analysis showed a higher CPPD prevalence on ultrasound than conventional radiology at the knee (only data available). Conclusion: Among all peripheral joints, the knees and wrists could be regarded as the target joints for CPPD detection by imaging. Furthermore, ultrasound seems to detect a higher number of calcium pyrophosphate deposits than conventional radiology, even when using a more restrictive reference standard.

Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients.

Cost-Effectiveness of the Early Arthritis Clinic Organizational Model.

OBJECTIVE: Early diagnosis and tight control improve outcomes of rheumatoid arthritis (RA). However, whether establishing an early arthritis clinic (EAC) is sustainable for national health systems is not known. This analysis aimed to compare effectiveness and costs of an EAC compared to patients followed by the current standard of care. METHODS: A retrospective study on administrative health databases of patients with a new diagnosis of RA was conducted: 430 patients followed in an EAC were enrolled, and 4 non-EAC controls were randomly matched for each. During 2 years of follow-up, the mean health care costs (outpatient, inpatient, pharmaceutical, and global) and 3 effectiveness measures (number and length of hospitalization and quality of care) of the EAC and non-EAC were estimated. The incremental cost-effectiveness ratio was calculated as well as the cost-effectiveness acceptability curve. RESULTS: The cohorts included patients with a mean age of 55.4 years, and 1,506 patients (70%) were female. The mean pharmaceutical (2,602 versus 1,945 euros) and outpatient (2,447 versus 1,778 euros) costs were higher in the EAC cohort. Conversely, a higher rate of non-EAC patients had a low adherence to quality-of-care indicators. The expected number of hospitalizations and the length of stay were statistically significantly higher in the non-EAC versus EAC. CONCLUSION: Despite an expected increase in outpatient costs (visits and diagnostic tests) and pharmaceutical costs, the reduction in terms of number and length of hospitalizations and the higher adherence to international quality-of-care guidelines support the effectiveness of the EAC model.

Novel insights into the management of rheumatoid arthritis: one year in review 2022.

New evidence for the treatment of rheumatoid arthritis (RA) has emerged during the last year. Specifically, updated guidelines on pharmacological and non-pharmacological management of RA have emphasised the necessity of global patient's care, and have shifted the role of some older drugs, such as glucocorticoids and methotrexate. In addition, the long-term safety of Janus kinase inhibitors was investigated and reinforced. With respect to the coronavirus-19 pandemic, reassuring data on the efficacy and safety of vaccinations in the RA population were acquired, as well as on the potential role of telemedicine in RA management. Machine learning prediction models and biomarkers development have emerged as promising innovations in the area of precision/personalised medicine, appearing to encourage future expansion.In this narrative review, the authors aim to give their specific point of view on the most relevant and potentially impacting novelties published during 2021 and early 2022 in the context of RA management.

C-reactive protein and 10-year cardiovascular risk in rheumatoid arthritis.

OBJECTIVES: To evaluate the association between C-reactive protein (CRP) and 10-year risk of cardiovascular (CV) events using the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), based on conventional and RA-specific risk factors but not CRP, in RA patients without previous cardiovascular events. METHODS: ERS-RA was calculated in 1,251 "Cardiovascular Obesity and Rheumatic Disease Study (CORDIS)" database patients [(age 60.4(9.3) years; 78% female; disease duration, 11.6(8) years; CDAI, 9(9); CRP, 6.8(12) mg/L]. RESULTS: The mean (SD) 10-year risk of CV events was 12.9% (10). After adjusting for the use of DMARDs and biologics, CRP concentrations were significantly associated with 10-year risk of CV events (coefficient=0.005 for each 10 mg/L CRP increment; 95%CI 0.000-0.111; p = 0.047). In mediation analysis, the association between CRP and ERS-RA was not explained by disease activity. CONCLUSION: In a large cohort of RA patients without previous cardiovascular events, a 20 mg/L increase in CRP concentrations was associated with a 1% increase in 10-year risk of CV events. This suggests that actively targeting residual inflammatory risk beyond conventional and RA-specific risk factors might further reduce CV event rates in RA patients.

Musculoskeletal Ultrasound to Identify Subclinical Joint and Periarticular Involvement in Patients With Inflammatory Bowel Disease: A Systematic Literature Review.

Background: Musculoskeletal ultrasonography identifies subclinical joint and entheseal inflammation, and it might be of value in patients with inflammatory bowel diseases (IBD), which are at higher risk of inflammatory arthropathy and disability. Our aim was to retrieve the evidence on the applications of ultrasound in patients with non-arthropathic IBD. Methods: Studies enrolling patients with IBD without arthritis, undergoing ultrasound of joints, tendons or entheses were eligible. The outcomes of interest encompassed the frequency of ultrasound-detected lesions, their accuracy in diagnosing arthritis, their prognostic role and sensitivity to change. All study types, excluding case reports, case series and narrative reviews, were included. Search strategies were applied in PubMed and Embase. Abstract and full-texts were evaluated by pairs of reviewers. The risk of bias was evaluated through the Newcastle-Ottawa scale or the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2. The protocol was registered in PROSPERO (CRD42021264972). Results: Out of 2,304 records, eight studies were included, all reporting the frequency of lesions, while only three evaluated also the diagnostic accuracy. All studies had a cross-sectional design, with no evidence on prediction or follow-up. All studies evaluated the entheses, while only three the joints. The most common chronic lesions were entheseal thickening (up to 81.5%) and enthesophytes (67.9%), while entheseal erosions were present in 16%-17% of patients. Among inflammatory lesions, power Doppler was reported in 14%-67% of patients. There were no differences among Crohn's disease or ulcerative colitis and depending on disease activity, while there were contrasting results on different disease durations. When evaluating the diagnostic performance, the best specificity for a diagnosis if IBD was 0.88 (95%CI, 0.8-0.94) for joint abnormalities. Also, the best sensitivity was 0.88 (95%CI, 0.76-0.95) for entheseal lesions. No studies assessed of the combination of lesions. Due to the limited number of studies, meta-analyses were not performed. Conclusions: Despite the possible value of ultrasound in IBD, there is limited evidence deriving from cross-sectional studies. Longitudinal studies are needed to clarify the role of this technique, while its current placement might be that of complementing clinical assessment, in particular in early intestinal disease.

Influence of initial glucocorticoid co-medication on mortality and hospitalization in early inflammatory arthritis: an investigation by record linkage of clinical and administrative databases.

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.

Inflammatory correlates of the Patient Global Assessment of Disease Activity vary in relation to disease duration and autoantibody status in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status. METHODS: 1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson's coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission). RESULTS: In patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30-0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18-0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status. CONCLUSIONS: In the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.