Established Rheumatoid Arthritis Research Articles

A study of carotid intima media thickness in patients with rheumatoid arthritis and its correlation with acute phase reactants and disease activity

Introduction: There is increased risk of cardiovascular morbidity and mortality in patients of rheumatoid arthritis (RA) due to accelerated atherosclerosis. In this study we measured Carotid artery intima media thickness (CIMT) as a surrogate marker for subclinical atherosclerosis in RA patients without pre-existing cardiovascular disease. This study also analyzed the correlation between CIMT, disease duration, Simplified Disease Activity Index (SDAI) and acute phase reactants. Methods: A cross-sectional study was conducted on 90 patients divided into two groups of 45 patients of RA and another 45 control subjects. Subjects with RA and age and sex matched healthy controls were included in the study without pre-existing CV risk factors. Complete clinical evaluation, hematological and biochemical profile done. ESR, CRP and platelet count were used as markers of acute phase reactants. All the RA patients included in the study were evaluated for their disease activity using Simplified Disease Activity Index (SDAI). All the subjects including the controls evaluated for carotid intima media thickness by using carotid ultrasonography. CIMT measured in common carotid artery bilaterally by examining throughout common carotid artery up to 2 cm proximal to bifurcation. CIMT measurement taken at the site of greatest thickness. All measurements taken in diastole, measured in phase when lumen diameter is at its smallest and IMT at its largest. Mean value of 6 readings (3 from each side) taken as final CIMT for evaluation. B mode (linear probe) USG was used to determine carotid IMT. Results: 45 cases and similar control subjects included in the study with mean age (SD) as 45.07 (14.81) years. We found female preponderance with 37 females out of 45 cases. Mean (SD) disease duration in male subjects was 5.38(2.40) years while in females was 5.09 (2.78) years. CRP was found to be significantly increased in cases group with mean (SD) of 5.75(8.85) mg/dl. ESR significantly raised to 35.22(13.55) mm/hour in cases group compared to control group where it was 16.16(5.71) mm/hr. Mean (SD) platelets (x10³/mm³) were 229.24(69.80) in cases while controls had 290.33(83.85), so platelets correlation with disease could not be established. CIMT was significantly raised in cases group. Mean (SD) CIMT in cases was 0.95(1.06) mm whereas in control group it was 0.60(0.16) mm with p value of 0.002. Moderate positive correlation was found between CIMT (mm) and SDAI and this correlation was statistically significant with p=0.001. For every 1 unit increase in CIMT, the SDAI increases by 2.92 units. A strong positive correlation between CIMT (mm) and Disease Duration (Years), and this correlation was statistically significant (rho = 0.9, p = <0.001). For every 1 unit increase in CIMT (mm), the Disease Duration (Years) increases by 1.26 units. Conversely, for every 1 unit increase in Disease Duration (Years), the CIMT (mm) increases by 0.19 units. Conclusion: A strong correlation was observed between CIMT and disease duration in rheumatoid arthritis. Hence, CIMT can be a useful surrogate marker for detecting atherosclerosis in patients with RA. In view of the relation to duration of disease, established RA patients should regularly be screened to identify the evidence of atherosclerosis and manage it earlier. Prevention of cardiovascular disease in RA requires an integrated approach encompassing cardiovascular risk factors screening and management, effective and sustained control of RA disease activity, high index of suspicion and prompt investigation of suspected cardiac disease.

Ultrasonographic Evaluation of the Ankle Joint in Relation to Rheumatoid Factor Status and Disease Activity in Patients with Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a form of inflammatory disease whose clinical pattern is largely dependent on the presence of both anti-citrullinated protein antibodies and rheumatoid factor (RF). Although this is still debatable, seronegative RA seems to be a somewhat less serious condition. The present study aimed to evaluate ankle joint ultrasound in relation to RF status and disease activity in RA patients. Methods: A cross-sectional study involving RA patients from a single center was conducted. Laboratory test evaluations and clinical activity assessments were carried out. The ankle joint was examined using musculoskeletal ultrasound (US). Results: The study included 100 patients with established RA in total. Eighty-two patients tested positive for RF with a mean age of 42.3, whereas only 18 tested negative with a mean age of 39.6. Patients who tested positive for RF had a longer duration of illness (9.39 ± 5.39 vs. 4.56 ± 3.24). There were no differences in clinical activity scores between the seropositive and seronegative groups. The pathological US findings of any ankle joint showed no differences between the seropositive and seronegative groups. Patients with US findings of tibialis posterior tenosynovitis in the left ankle and synovitis and erosion in the right ankle, particularly in the tibiotalar and talonavicular joints, had significantly high Disease Activity Score 28-Erythrocyte sedimentation rate-scores. The increased disease activity was accompanied by significant erosions on both ankles. Conclusion: In terms of disease activity, there is no clinically significant difference between seropositive and seronegative RA patients. Sonographic ankle joint abnormalities do not appear to be associated with the patients’ RF status. High RA disease activity, on the other hand, is associated with synovitis and erosions, particularly in the talonavicular and tibiotalar joints, as well as tibialis posterior tenosynovitis.

Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis.

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of these 815 genes were most robustly expressed by lining layer synovial fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human lining layer fibroblasts and human dorsal root ganglion neurons expressing calcitonin gene-related peptide (CGRP+). Both RA synovial fibroblast culture supernatant and netrin-4, which is abundantly expressed by lining fibroblasts and was within the GbGMI-identified pain-associated gene module, increased the branching of pain-sensitive murine CGRP+ dorsal root ganglion neurons in vitro. Imaging of solvent-cleared synovial tissue with little inflammation from humans with RA revealed CGRP+ pain-sensing neurons encasing blood vessels growing into synovial hypertrophic papilla. Together, these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA.

Responsiveness and sensitivity of PROMs to change in disease activity status in early and established rheumatoid arthritis.

To determine whether patient reported outcome measures (PROMs) capturing activity limitations, health impact, pain, fatigue and work ability are responsive and sensitive to changes in disease activity status in patients with early and established rheumatoid arthritis (RA). All early RA patients (n = 557) from the tREACH-trial and established RA patients (n = 188) from the TARA-trial were included. Both studies were multicentre, single-blinded trials with a treat-to-target management approach. The following PROMs were studied: Health Assessment Questionnaire Disability Index(HAQ-DI), morning stiffness severity, EQ-5D, general health, 36-item short form(SF-36), joint pain, fatigue and productivity loss. Mean changes in PROMs between two consecutive visits were compared with changes in disease activity status(remission, low disease activity and active disease) using linear mixed models and standardised response means. Additionally, the proportion of individual observations that showed an expected PROM response to disease activity status alterations was calculated. HAQ-DI, morning stiffness severity, general health, EQ-5D and joint pain demonstrated responsiveness to improvement or worsening of disease activity status in both early and established RA. SF-36 physical and mental component scale, fatigue and productivity loss did not show this effect in both groups. Across nearly all PROMs, the magnitude of change and the proportion of individual observations that reflect a shift from and to active disease remained low. HAQ-DI, morning stiffness severity, EQ-5D, general health and joint pain are responsive to disease activity status alterations on a group level in both early and established RA. For the individual patient the responsiveness of these PROMs is poor. tREACH trial (www.isrctn.com, ISRCTN26791028) and TARA trial (www.onderzoekmetmensen.nl, NTR2754).

Classifying Multimorbidity Using Drug Concepts via the Rx-Risk Comorbidity Index: Methods and Comparative Cross-Sectional Study.

The study objective was to update a method to identify comorbid conditions using only medication information in circumstances in which diagnosis codes may be undercaptured, such as in single-specialty electronic health records (EHRs), and to compare the distribution of comorbidities across Rx-Risk versus other traditional comorbidity indices. Using First Databank, RxNorm, and its web-based clients, RxNav and RxClass, we mapped Drug Concept Unique Identifiers (RxCUIs), National Drug Codes (NDCs), and Anatomical Therapeutic Chemical (ATC) codes to Rx-Risk, a medication-focused comorbidity index. In established rheumatoid arthritis (RA) and osteoarthritis (OA) cohorts within the Rheumatology Informatics System for Effectiveness registry, we then compared Rx-Risk with other comorbidity indices, including the Charlson Comorbidity Index, Rheumatic Disease Comorbidity Index (RDCI), and Elixhauser. We identified 965 unique ingredient RxCUIs representing the 46 Rx-Risk comorbidity categories. After excluding dosage form and ingredient related RxCUIs, 80,911 unique associated RxCUIs were mapped to the index. Additionally, 187,024 unique NDCs and 354 ATC codes were obtained and mapped to the index categories. When compared to traditional comorbidity indices in the RA cohort, the median score for Rx-Risk (median 6.00 [25th percentile 2, 75th percentile 9]) was much greater than for Charlson (median 0 [25th percentile 0, 75th percentile 0]), RDCI (median 0 [25th percentile 0, 75th percentile 0]), and Elixhauser (median 1 [25th percentile 1, 75th percentile 1]). Analyses of the OA cohort yielded similar results. For patients with a Charlson score of 0 (85% of total), both the RDCI and Elixhauser were close to 1, but the Rx-Risk score ranged from 0 to 16 or more. The misclassification and under-ascertainment of comorbidities in single-specialty EHRs can largely be overcome by using a medication-focused comorbidity index.

Perceived Access to Health Care of Indigenous Peoples in Canada with Rheumatoid Arthritis and their First-Degree Relatives.

There are complex and interrelated factors that lead to inequitable healthcare delivery in Canada. Many of the factors that underlie these inequities for Canada's geographically dispersed Indigenous Peoples remain underexamined. A cohort of 831 First Nations (FN) individuals from urban and remote communities were recruited into a longitudinal study of rheumatoid arthritis (RA) risk from 2005-2017. Data from each participant's initial enrollment visit was assessed using a survey that captured concerns with health care access. We found that remote participants with RA reported poor access compared to remote First-Degree Relatives (FDR, p<0.001), this difference was not observed for urban RA participants. We observed substantial differences based on sex; Females perceived access to care to be more difficult than males in both urban and remote cohorts (p<0.001). We also observed that male participants with RA reported poor access to care compared to male FDR. Importantly, access to care in remote communities appeared to improve over the duration of the study (p=0.01). In a logistic regression analysis, female sex, remote location, and older age were independent predictors of poor access to care. Predictors of poor access in participants with RA were also female sex, remote location and older age. FN peoples living in remote communities, particularly those with an established RA diagnosis, report more problems accessing healthcare. Sex-based inequities exist, with FN females reporting greater difficulties in accessing appropriate healthcare, irrespective of RA diagnosis. Addressing these sex-based inequities should be a high priority for improving healthcare delivery.

Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

The Impact of Occupational Therapy on the Self-Management of Rheumatoid Arthritis: A Mixed Methods Systematic Review.

To determine the impact of occupational therapy (OT) on the self-management of function, pain, fatigue, and lived experience for people living with rheumatoid arthritis (RA). Five databases and gray literature were searched up to June 30, 2022. Three reviewers screened titles and abstracts, with two independently extracting and assessing full texts using the Cochrane risk of bias (quantitative) and Critical Appraisal Skills Programme (qualitative) tools to assess study quality. Studies were categorized into four intervention types. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (quantitative) and GRADE- Confidence in Evidence from Reviews of Qualitative research (qualitative) were used to assess the quality of evidence for each intervention type. Of 39 eligible papers, 29 were quantitative (n=2,029), 4 qualitative (n=50), and 6 mixed methods (n=896). Good evidence supports patient education and behavior change programs for improving pain and function, particularly group sessions of joint protection education, but these do not translate to long-term improvements for RA (>24 months). Comprehensive OT had mixed evidence (limited to home OT and an arthritis gloves program), whereas limited evidence was available for qualitative insights, splints and assistive devices, and self-management for fatigue. Although patient education is promising for self-managing RA, no strong evidence was found to support OT programs for self-managing fatigue or patient experience and long-term effectiveness. More research is required on lived experience, and the long-term efficacy of self-management approaches incorporating OT, particularly timing programs to meet the individual's conditional needs (i.e., early or established RA) to build on the few studies to date.

Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells

BackgroundInvolvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction.MethodsSeventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry.ResultsCompared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL).ConclusionsCartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.

Integrative non-pharmacological care for individuals at risk of rheumatoid arthritis.

There is increasing knowledge in the recognition of individuals at risk for progression to rheumatoid arthritis (RA) before the clinical manifestation of the disease. This prodromal phase preceding the manifestation of RA may represent a "window of opportunity" for preventive interventions that may transform the clinical approach to this disease. However, limited evidence exists in support of effective interventions to delay the onset or even halt the manifestation of RA. Given the multifactorial nature of RA development and disease progression, the latest guidelines for established RA stress the use of integrative interventions and multidisciplinary care strategies, combining pharmacologic treatment with non-pharmacological approaches. Accordingly, individuals at risk of RA could be offered an integrative, multifactorial intervention approach. Current data point toward pharmacological intervention reverting the subclinical inflammation and delay in the disease onset. In addition, targeting life style modifiable factors (smoking cessation, dental health, physical activity, and diet) may presumably improve RA prognosis in individuals at risk, mainly by changes in epigenetics, autoantibodies, cytokines profiles, and microbiome. Nonetheless, the benefits of multidisciplinary interventions to halt the manifestation of RA in at-risk individuals remain unknown. As there is a growing knowledge of possible pharmacological intervention in the preclinical phase, this narrative review aims to provide a comprehensive overview of non-pharmacological treatments in individuals at risk of RA. Considering the mechanisms preceding the clinical manifestation of RA we explored all aspects that would be worth modifying and that would represent an integrative non-pharmacological care for individuals at risk of RA.

Personalised care packages for people with rheumatoid arthritis: a mixed-methods study

ObjectivesDisease management in rheumatoid arthritis (RA) requires holistic assessment. We aimed to design personalised care packages suitable for people with RA.MethodsThis study was conducted using a mixed-methods approach and exploratory...

Tibialis Posterior Tenosynovitis as a First Presenting Feature of Pre-clinical Rheumatoid Arthritis: A Case Report and Literature Review

Tenosynovitis in Preclinical Rheumatoid Arthritis (RA) has been reported. The Tibialis posterior (TP) tendon is the second most commonly affected tendon in the foot and ankle in established RA, but in preclinical RA has not been reported. In this case report, we present a 27-year old lady from Dhading, Nepal, with Preclinical RA with first presentation with Tibialis posterior Tenosynovitis. She was anti-cyclic citrullinated Peptide (CCP) positive but had no arthralgia or morning stiffness. Initial treatment with Non-Steroidal anti-inflammatory drugs failed to alleviate her symptoms. Methotrexate helped improve her symptoms. Keywords: Methotrexate; Rheumatoid Arthritis; Tenosynovitis; Tibialis Posterior Dysfunction

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study

ObjectivesThe aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS). MethodsThirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs. ResultsFrom baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation. ConclusionChanges in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation.

The correlation between 4 adherence measurements methods in patients with rheumatoid arthritis using methotrexate.

Methotrexate (MTX) is the cornerstone in the treatment of rheumatoid arthritis (RA) patients. However, adherence to MTX therapy is not optimal, and instruments to assess medication nonadherence are warranted. To date there is no consensus on the best method to determine adherence to MTX. The aim of this study was to assess the correlation between adherence assessed with a Medication Event Monitoring System (MEMS) vs. pill count, MTX-polyglutamate (PG) concentration and Compliance Questionnaire-Rheumatology (CQR) in patients with established RA. Second, the correlations between these methods and the Disease Activity Scores of 28 joints (DAS28) were examined. Adult RA patients currently treated with MTX were included. Multivariable linear and logistic regression were used, with adherence assessed with MEMS as dependent variable vs. pill count, MTX-PG concentrations, CQR as independent variables and DAS28 vs. each of the 4 adherence measurements. Covariates were included, such as comedication, age and use of corticosteroids. In total, 190 consecutive RA patients were included. Pill count was correlated with adherence assessed with MEMS (linear regression, β =0.588, 95% confidence interval =0.255-0.921, P< .001), whereas CQR and MTX-PGs were not. Logistic regression confirmed the correlation between dichotomized adherence and pill count only (β =4.47, 95% confidence interval =1.31-7.64, P= .006). No other correlations were found, either for all adherence outcomes or DAS28. Measuring adherence with MEMS is correlated with pill count, whereas other methods were not correlated with MEMS or with DAS28. Pill count can be used to estimate adherence to MTX therapy, in case MEMS is not achievable.

Anti-Peptidylarginine Deiminase 4 Autoantibodies and Disease Duration as Predictors of Treatment Response in Rheumatoid Arthritis.

Given that autoantibodies to peptidylarginine deiminase 4 (PAD4) are associated with erosive disease in established rheumatoid arthritis (RA), this study was conducted to compare the clinical and prognostic use of anti-PAD4 antibodies in patients with early and established RA. Sera from patients with early (duration <2 years; n=422) or established (duration ≥2 years; n=359) RA from two randomized clinical trials of tofacitinib ± methotrexate compared with adalimumab + MTX or MTX alone were evaluated for the presence of anti-PAD4 and anti-PAD3/4 antibodies at baseline and posttreatment time points. Summary statistics were calculated for demographic, clinical, and serological characteristics, and generalized estimating equations were used to model clinical outcomes by disease duration according to anti-PAD4 status. Anti-PAD4 antibodies were present in 22% and 40% of patients with early and established RA, respectively, stable following treatment, and associated with baseline joint damage only in established RA. In early RA, baseline anti-PAD4 antibodies were associated with a greater improvement in disease activity score 28-joint count using C-reactive protein levels after treatment compared with individuals with negative anti-PAD4 (P = 0.049). Tofacitinib ± MTX was more broadly efficacious than MTX alone at improving clinical outcomes in early and established RA, irrespective of anti-PAD4 status (P < 0.05 for all), whereas adalimumab + MTX exhibited differential benefits in achieving disease activity score remission in early RA (P = 0.036) and American College of Rheumatology 20 responses in established RA (P = 0.002). Differences in prevalence, clinical associations, and treatment-response outcomes according to anti-PAD4 antibody status in early and established RA suggests the existence of a therapeutic window to prevent the accumulation of irreversible joint damage in early patients with RA with anti-PAD4 antibodies.

EE729 Early Intervention With Biosimilars Compared With Leflunomide in Established Rheumatoid Arthritis: A Cost-Effectiveness Analysis in Hong Kong

EE729 Early Intervention With Biosimilars Compared With Leflunomide in Established Rheumatoid Arthritis: A Cost-Effectiveness Analysis in Hong Kong

Performance of Anti-Carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis from a Single Center.

Detection of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) in sera support the diagnosis of rheumatoid arthritis (RA); however, these markers are not detected in about 20% of RA patients. More recently, antibodies against carbamylated proteins (anti-CarP) have emerged with implications for preclinical RA diagnosis. The objective of this study was to assess the clinical performance of anti-CarP and correlate with disease severity in routine clinical practice. Retrospective chart review of 331 subjects submitted for RA panel serology: 136 clinically defined RA-positive and 195 RA-negative patients. Fifty additional individuals were recruited for healthy controls. Patients' sera were tested for anti-CCP, anti-CarP, and RF antibodies. Clinical performance characteristics were evaluated for anti-CarP individually and in combination with anti-CCP and RF. Documented erosions and synovitis were correlated with anti-CarP positivity. Anti-CarP had a clinical sensitivity and specificity of 27% and 94%, respectively, for established RA. This sensitivity was lower than anti-CCP (79%) and RF (85%). The specificity of anti-CarP was similar to anti-CCP (93%) and higher than RF (69%). Anti-CarP in combination with anti-CCP and RF increased specificity (100%) but decreased sensitivity (21%). There was no correlation of anti-CarP positivity with presence of bone erosions; however, there was an increase in anti-CarP positivity among patients with synovitis. Anti-CarP demonstrates high specificity in diagnosis of established RA but lacks clinical sensitivity. In combination, anti-CarP does not improve clinical performance of anti-CCP and RF but may be useful in anti-CCP negative patients and in identifying patients with more active disease.

Abstract 5 — Prediction of Flare Following Glucocorticoids Withdrawal in Rheumatoid Arthritis Patients with Continuation of csDMARDs: A Real-Life Study

Background In patients with rheumatoid arthritis (RA), glucocorticoids (GC) should be firstly discontinued before considering tapering conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) or other biological agents. We aim to determine risk factors for flare after GC withdrawal in RA patients undergoing csDMARDs. Method RA patients who discontinued GC with continuation of csDMARD were selected from a longitudinal real-world cohort. Established RA was defined as disease duration over 12 months. Dissatisfied RA control was defined as the proportion of simplified disease activity index (SDAI)-based remission time to total time from GC initiation to discontinuation less than 50%. Logistic regression was used to analyze the independent risk factors for flare after GC discontinuation and results were expressed as odds ratio (OR). Results There were 115 eligible RA patients discounted GC with continuation of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, 24 patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs. 49%, p=0.025), higher median cumulative prednisolone dosages (3.3g vs. 2.2g, p=0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs. 33%, p=0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone dose &gt; 2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). Flare risk was increased with increases in number of risk factors, with highest OR of 11.56 in patients with three risk factors (p for trend=0.002). Conclusions Flare following GC withdrawal is not common in RA patients with undergoing csDMARDs therapy. Established RA, higher cumulative GC dose and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal.

Glucocorticoid trajectories over 2 years in patients with rheumatoid arthritis in a real-life setting

ObjectivesTo analyse glucocorticoid (GC) use and trajectories in a real-life cohort of rheumatoid arthritis (RA).MethodsPatients with RA included in the longitudinal RCVRIC cohort for initiating or changing biological disease-modifying antirheumatic...

The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis: Individual Patient Data From Five Randomized Trials.

Weight gain and hypertension are well known adverse effects of treatment with high-dose glucocorticoids. To evaluate the effects of 2 years of low-dose glucocorticoid treatment in rheumatoid arthritis (RA). Pooled analysis of 5 randomized controlled trials with 2-year interventions allowing concomitant treatment with disease-modifying antirheumatic drugs. 12 countries in Europe. Early and established RA. Glucocorticoids at 7.5 mg or less prednisone equivalent per day. Coprimary end points were differences in change from baseline in body weight and mean arterial pressure after 2 years in intention-to-treat analyses. Difference in the change of number of antihypertensive drugs after 2 years was a secondary end point. Subgroup and sensitivity analyses were done to assess the robustness of primary findings. A total of 1112 participants were included (mean age, 61.4 years [SD, 14.5]; 68% women). Both groups gained weight in 2 years, but glucocorticoids led, on average, to 1.1 kg (95% CI, 0.4 to 1.8 kg; P<0.001) more weight gain than the control treatment. Mean arterial pressure increased by about 2 mm Hg in both groups, with a between-group difference of -0.4 mm Hg (CI, -3.0 to 2.2 mm Hg; P= 0.187). These results were consistent in sensitivity and subgroup analyses. Most patients did not change the number of antihypertensive drugs, and there was no evidence of differences between groups. Body composition was not assessed, and generalizability to non-European regions may be limited. This study provides robust evidence that low-dose glucocorticoids, received over 2 years for the treatment of RA, increase weight by about 1 kg but do not increase blood pressure. None.