Longer Rheumatoid Arthritis Duration Research Articles

Pengaruh Emosi Positif Terhadap Hasil Pengobatan Penyakit Rheumatoid Arthritis

This study evaluates the impact of positive emotions on rheumatoid arthritis (RA) treatment outcomes through a meta-analysis of 47 studies (2015-2024) involving 12,384 patients. The primary findings reveal a significant positive correlation between positive emotions and improved RA treatment outcomes (r = 0.42, p < 0.001), with the strongest effects observed in enhanced quality of life (r = 0.51) and physical function (r = 0.45). Patients exhibiting high positive emotions demonstrated greater reductions in pain (d = 0.38), decreased inflammation (d = 0.29), and improved physical function (d = 0.45) compared to control groups. Moreover, moderator analyses uncovered stronger effects among elderly patients (? = 0.012, p = 0.025) and those with longer RA duration (? = 0.018, p = 0.009). Finally, mediational analyses indicated that positive emotions contributed to improved treatment adherence (indirect effect = 0.09, 95% CI [0.05, 0.13]) and increased physical activity (indirect effect = 0.07, 95% CI [0.03, 0.11]) in RA patients. These findings extend Fredrickson's (2001) Broaden-and-Build theory and support Keefe et al.'s (2002) biopsychosocial model. Compared to meta-analyses by Brosseau et al. (2018) and Zhou et al. (2020), this study provides more comprehensive evidence on the role of positive emotions in various RA treatment outcomes. The novelty of this research lies in the analysis of previously unexplored mediating and moderating mechanisms, as well as a comparison of effectiveness with pharmacological interventions (SMD = 0.18, 95% CI [-0.05, 0.41], p = 0.124). These results support the integration of positive emotion-based interventions in RA management and expand upon Strand et al.'s (2019) findings on patient expectations in RA treatment.

The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

Background Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. Materials and Methods To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger’s test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. Results A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8–21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70–2.16), older age (WMDs = 6.89, 95% CI 3.10–10.67), having a smoking history (ORs =1.91, 95% CI 1.48–2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89–2.30), longer RA duration (ORs = 1.03, 95% CI 1.01–1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63–8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65–2.68), positive ACPA (ORs = 2.11, 95%CI 1.65–2.68), higher ESR (ORs = 1.008, 95%CI 1.002–1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36–2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08–1.87) and steroid use (HRs= 1.70, 1.13–2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69–0.87). Conclusion(s) The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

Osteoporosis-related fractures in men and women with established and early rheumatoid arthritis: predictors and risk compared with the general population

ObjectivesTo study the risk of osteoporosis-related fractures in a community-based sample of men and women with rheumatoid arthritis (RA) overall, as well as early (< 1 year of disease duration, follow-up time maximum 10 years) and established (RA diagnosis since ≥ 5 years on July 1, 1997) RA, compared with the general population. To study potential risk factors for fractures in patients with RA from baseline questionnaire data.MethodsA community-based cohort of patients with RA (n = 1928) was studied and compared to matched general population controls. Information on osteoporosis-related fractures (hip, proximal upper arm, distal forearm and vertebral fractures) during the period July 1, 1997 to December 31, 2017 was obtained by linkage to the Swedish National Inpatient Register and the Cause of Death Register. The incidence of fractures was estimated in patients and controls. Cox regression models were used to assess the relation between RA and the risk of fractures and to assess potential predictors of fractures in RA patients. Analyses were stratified by sex, and performed in all patients with RA, and in subsets with early and established RA.ResultsThe overall incidence of osteoporosis-related fractures in the RA cohort was 10.6 per 1000 person-years (95% CI 9.31; 12.0). There was an increased risk of fractures overall in both men (hazard ratio (HR) 1.55, 95% CI 1.03; 2.34) and women (HR 1.52; 95% CI 1.27; 1.83) with RA compared to controls, with significantly increased risk also in the hip. No increased risk of osteoporosis-related fractures overall was seen in patients with early RA (HR 1.01, 95% CI 0.69; 1.49). Higher age, longer duration of RA, higher HAQ scores and higher scores in the visual analogue scale for global health were predictors of fractures.ConclusionBoth men and women with RA were at increased risk of osteoporosis-related fractures. Patients with early RA did not have significantly increased risk during the first 10 years of disease in this study.

Long-term use of glucocorticoids in patients with active rheumatoid arthritis: therapeutic "freeze frame"

In Russia, as well as throughout the world, the use of glucocorticoids (GC) in the treatment of rheumatoid arthritis (RA) is widespread, often going beyond the recommendations for both duration and dose regimen, which makes it relevant to study the long-term consequences of such a "wrong" (EULAR, 2022) use of GC in RA therapy. Of 1143 patients with active RA (ACR/EULAR 2010), two groups were formed: A (n=782) RA patients with more than 6 months of experience with systemic GC; group B (n=245) - no experience of taking GC. The cumulative disease index (CIRS) was used to assess the comorbidity profile. Patients in group A were older (p<0.0001), with a longer duration of RA (p=0.0004) and more often with IV radiological stage (p=0.02). With comparable (DAS28) RA activity, the D2T variant of RA was more often detected in them (p=0.036). RA therapy in group A was characterized by a large number of used disease-modifying anti-rheumatic drugs (p=0.0003), more frequent development of methotrexate-induced hepatitis (p=0.03). In group A, the time interval between the onset of RA and the initiation of biological therapy was longer (p=0.0001) and directly correlated with the duration of GC therapy (Rs=0.38) with a comparable qualitative structure of the used b/tsDMARDs. In the same group, tuberculosis, hypertension, chronic kidney disease, cataract and osteoporosis (p<0.05) and its complications were diagnosed significantly more often with a comparable frequency of cardiovascular disease, diabetes, and gastrointestinal lesions. In group A, a higher CIRS multimorbidity index was detected, and the CIRS severity index was lower than in group B (p<0.05). Long-term use of GC did not lead to a decrease in disease activity, inhibition of radiographic progression, delayed the timely administration of b/tsDMARDS and was accompanied by an increase in the multimorbid load.

Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis.

Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is a potentially life-threatening complication with significant morbidity and mortality. This meta-analysis aims to systematically determine the factors associated with the development of rheumatoid arthritis-related interstitial lung disease (RA-ILD). All primary studies which reported the factors associated with of RA-ILD were eligible for the review except case reports. The Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), and WANFANG electronic databases were searched through to December 30, 2022, for studies investigating the factors associated with RA-ILD. The methodological quality assessment of the eligible studies was performed using the Newcastle-Ottawa Scale (NOS). 2 reviewers extracted relevant data independently. Then, weighed mean differences (WMDs) or pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between the factors and RA-ILD. The statistical meta-analysis, subgroup and sensitivity analyses were performed using the Review Manager 5.3, and publication bias with Egger's test were performed using the Stata12.0 software. A total of 22 articles were screened for a meta-analysis which involved 1887 RA-ILD patients and 8066 RA without ILD patients. Some identified factors that were associated with an increased risk of RA-ILD included male sex (OR = 1.92, 95% CI: 1.54-2.39; P < 0.00001), older age (WMD = 5.77 years, 95% CI: 3.50-8.04; P < 0.00001), longer duration of RA (WMD = 0.80 years, 95% CI 0.12-1.47; P = 0.02), older age at onset of RA (WMD = 6.41 years, 95% CI: 3.17-9.64; P = 0.0001), smoking (OR = 1.69, 95% CI: 1.30-2.18; P < 0.0001). Five factors of laboratory items associated with the development of RA-ILD were evaluated in the meta-analysis. Compared with RA without ILD patients, positive rheumatoid factor (RF) (OR = 1.72, 95% CI: 1.47-2.01; P < 0.00001) and positive anti-citrullinated protein antibodies (ACPA) (OR = 1.58, 95% CI: 1.31-1.90; P < 0.00001) increased the risk of RA-ILD. Meanwhile, RF titer (WMD = 183.62 (IU/mL), 95% CI: 66.94-300.30; P = 0.002) and ACPA titer (WMD = 194.18 (IU/mL), 95% CI: 115.89-272.47; P < 0.00001) were significantly associated with increased risk of RA-ILD. Elevated erythrocyte sedimentation rate (ESR) (WMD = 7.41 (mm/h), 95% CI: 2.21-12.61; P = 0.005) and C-reactive protein (CRP) (WMD = 4.98 (mg/L), 95% CI: 0.76-9.20; P = 0.02) were also significantly associated with the development of the RA-ILD, whereas antinuclear antibody (ANA) positive status was not significantly associated with increased risk of RA-ILD (OR = 1.27, 95% CI: 1.00-1.60; P = 0.05). This meta-analysis showed that male gender, older age, longer duration of RA, older age at onset of RA, smoking, positive RF, positive ACPA, elevated RF titer, elevated ACPA titer, higher ESR and higher CRP were associated with RA-ILD.

Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures

Objective Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. Method This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. Results The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model’s discriminative ability. Conclusion Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis.

Some patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal. The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA) was a phase III, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate (MTX) + etanercept (ETN). If remission (Simplified Disease Activity Index [SDAI] ≤ 3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive MTX monotherapy, ETN monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods. Of 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of MTX treatment, and less severe clinical disease variables. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower patient global assessment of disease activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the MTX arm, shorter duration of ETN treatment, and lower magnesium. These findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with increased likelihood of remaining in remission/LDA with MTX or ETN monotherapy. (SEAM-RA; ClinicalTrials.gov: NCT02373813).

Factors associated with interstitial lung disease and the progressive fibrosing phenotype in rheumatoid arthritis–related interstitial lung disease

BackgroundThe risk factors for interstitial lung disease (ILD) in rheumatoid arthritis (RA) are inconsistent among previous studies. Furthermore, the factors associated with the emergence of the recently defined progressive fibrosing (PF) phenotype are unknown. Herein, we analyze the risk factors for ILD in RA. We also analyze the factors associated with a PF phenotype. MethodsWe collected the clinical and laboratory details of subjects with RA with (cases) or without (controls) ILD. Scoring of high-resolution computed tomography (HRCT) features of ILD was performed. We identified the subgroup that developed the PF phenotype during follow-up. We analyzed the factors associated with ILD using logistic regression (primary objective). We also compared the characteristics of ILD subjects with or without the PF phenotype (secondary objective). ResultsWe included 60 subjects (30 cases, 30 controls). Subjects with ILD had higher age, lower body mass index, longer duration of RA, and poorer lung function than the controls. Age (p = 0.007) and the duration of RA (p = 0.049) were the only significant predictors of ILD on univariate and multivariate analysis, respectively. Six (20%) subjects with RA-ILD developed a PF phenotype. These subjects were older, had greater frequency of honeycombing, and higher HRCT scores for honeycombing and aggregate fibrosis than those without the PF phenotype. Among subjects with honeycombing, 41.7% developed the PF phenotype. ConclusionsRA-ILD was associated with the duration of RA and age. Subjects with the PF phenotype were older and had higher honeycombing and fibrosis scores on HRCT chest.

Long-term outcomes after discontinuing biological drugs and tofacitinib in patients with rheumatoid arthritis: A prospective cohort study.

This study examined long-term outcomes of biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib discontinuation in patients with rheumatoid arthritis (RA). Ninety-seven RA patients who desired drug discontinuation after sustained remission or low disease activity for at least 48 weeks due to stable treatment with biological drugs or tofacitinib were enrolled into this study. All patients were prospectively followed until disease flare or the end of the study. Discontinued drugs (previous drugs) were reintroduced to treat flares. Following bDMARD/tofacitinib discontinuation (mean follow-up, 2.1 years; standard deviation, 2.0), disease flare occurred at a crude incidence rate of 0.36 per person-year. The median time to flare was 1.6 years (95% confidence interval [CI] 0.9-2.6), and the cumulative flare probability was estimated to be 45% at 1 year, 64% at 3 years, and 80% at 5 years. No or little radiological progression was shown in 87.1% of patients who maintained remission for 3 years. A Fine‒Gray competing risk regression analysis showed that predictive factors for a flare were longer RA duration at the start of bDMARD/tofacitinib treatment, previous failure of treatment with bDMARDs, and a shorter period of remission or low disease activity before drug discontinuation. Type of discontinued drug was not identified as a predictive factor after adjusting for other predictor variables. Restarting previous treatment regimens led to rapidly regaining disease control in 89% of flare patients within 1 month. Discontinuation of bDMARD/tofacitinib may be a feasible strategy in RA patients, especially patients with early treated and longer-controlled RA. Flares are manageable in most RA patients and radiological progression is rare for at least 3 years in patients with sustained remission after bDMARD/tofacitinib discontinuation.

Menopause and rheumatoid arthritis as factors associated with osteoporosis development

The aim of the research. To study the role of menopause, glucocorticoids (GCs) intake and characteristics of rheumatoid arthritis (RA) in development of osteoporosis (OP) and osteoporotic fractures. Material and methods. A total of 73 female RA patients in menopause were examined. The control group included 29 female RA patients in premenopause. In addition to standard clinical and laboratory examinations, P1NP, 25(OH)D, CTX-1 were measured, dual-energy x-ray absorptiometry and x-ray of the thoracic and lumbar spine were performed. Statistical analysis was performed using the “Statistica 12.0” software package. Results. Premenopausal patients had lower BMI. Patients in postmenopause had higher rate of OP (42 patients) than the controls (8 patients) (57.5% vs 27.6%, respectively). Among patients in postmenopause, OP was associated with lower BMI (27.6 vs 30.5 kg/m2), higher cumulative dose of GCs (6.9 vs 1.65 g), higher duration of GCs intake (32 vs 18 months), lower RA activity (3.37 vs 3.9 according to DAS28-CRP) and lower CTX-1 level (0.52 vs 0.7 ng/ml). In the same group, osteoporotic fractures were only associated with longer GCs intake (32 vs 24 months). In premenopause patients, OP was associated with longer RA duration (21 vs 6 months), cumulative dose of GCs (13.9 vs 0.45 g), duration of GCs intake (48 vs 3 months), higher level of hs-CRP (46 vs 8 mg/l) and lower P1NP level (51.8 vs 43.8 ng/ml). Osteoporotic fractures in premenopause were associated with RA duration (28 vs 6 months), cumulative dose of GCs (12.5 vs 1.2 g) and lower BMD in all examined areas. Conclusion. The OP rate was higher in postmenopause patients. In both groups, the duration of GCs intake and accumulated dose of GCs were associated with OP. In postmenopause, OP was also associated with lower BMI. In premenopause, OP and osteoporotic fractures were associated with longer RA duration, cumulative dose of GCs and lower BMD in all studied areas.

Effect of Irregular Treatment on Severity of Osteoporosis in Rheumatoid Arthritis Patients

Background:Rheumatoid arthritis is a chronic systemic inflammatory disorder that is associated with progressive disability and systemic complications. One of these complications is osteoporosis. Patients with severe osteoporosis have one or more fragility fractures in addition to T-score -2.5 or lower. Osteoporosis is more prevalent in rheumatoid arthritis patients who have higher disease activity. Objective: To show the effect of irregular treatment in patients with rheumatoid arthritis on the severity of osteoporosis. Patients and Methods: A cross-sectional study enrolled a total of 40 female patients who had rheumatoid arthritis. The data collected from patients include disease duration, disease activity and patients’ compliance to their drugs. They were sent to dual-energy x- ray absorptiometry scan and results were recorded. Results: The mean age was 45.95 ± 10.0 years; 45% of them had rheumatoid arthritis for less than five years; 55% had a low level of disease activity; and 65% of them had received treatment irregularly. Osteoporosis was diagnosed in 60% of them and 41.7% of them had severe osteoporosis. The highest prevalence of osteoporosis among patients with rheumatoid arthritis was seen significantly among older patients, patients with longer duration of rheumatoid arthritis, those with higher activity of rheumatoid arthritis, and those with irregular treatment. More than half of those who received treatment irregularly had severe osteoporosis with a significant association between treatment regularity of rheumatoid arthritis and severity of osteoporosis. Conclusion: Severe osteoporosis occurs in rheumatoid arthritis patients with a history of irregular treatment which occurs either due to patient incompliance or delay in diagnosis. Osteoporosis is more prevalent in rheumatoid arthritis patients with longer disease duration, older age, higher disease activity and those who received treatment irregularly. Keywords: Rheumatoid arthritis, Osteoporosis, Irregular Treatment

A Comparison of Demographics, Disease Activity, Disability, and Treatment Among Rheumatoid Arthritis Patients with and without Osteoporosis.

IntroductionOsteoporosis (OP) is one of the most common comorbidities associated with rheumatoid arthritis (RA). Literatures reported that the risk for developing OP was strongly associated with duration and severity of RA. We aim to elaborate on the consequences of OP on disease activity and management plan in patients with RA.Patients and MethodsA retrospective cohort study recruited 408 patients, including those with RA alone and with RA plus OP. The RA disease activity in the patients was assessed using disease activity score in 28 joints (DAS28-CRP). A statistical analysis was performed to compare data between the two groups of patients and determine any significant risk factor associated with the development of OP in RA patients.ResultsOf 408 patients who were included in this study, 353 patients (86.5%) had only RA, while 55 patients (13.5%) had RA with OP and showed significant difference (P = 0.04) concerning age categories. Patients diagnosed with RA and OP had RA duration longer than RA-only patients (independent t-test, P = 0.01). The two groups had almost similar disease activity at the three clinical visits, as well, had nearly similar disability at their first visit, whereas RA with OP patients had significant greater disability at their 2nd and 3rd visits (independent t-test, P = 0.001). Both groups were treated with the same biologic and non-biologic medication of similar frequency, although RA patients with OP received steroid more frequently than patients had RA only (61.7% vs. 41.7%, chi square test, P = 0.03).ConclusionThere was no significant difference in disease activity at both groups of patients. However, RA with OP group had longer duration of RA, were more frequently treated with steroids, and had greater disability. We recommend physicians focus on controlling RA disease activity, early screening for and treating of OP.

Data-Driven Patient Clustering and Differential Clinical Outcomes in the Brigham and Women's Rheumatoid Arthritis Sequential Study Registry.

ObjectiveTo use unbiased, data‐driven, principal component (PC) and cluster analysis to identify patient phenotypes of rheumatoid arthritis (RA) that might exhibit distinct trajectories of disease progression, response to treatment, and risk for adverse events.MethodsPatient demographic, socioeconomic, health, and disease characteristics recorded at entry into a large, single‐center, prospective observational registry cohort, the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), were harmonized using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. The resulting PCs were used to cluster patients using a K‐means approach. Longitudinal clinical outcomes were compared between the clusters over 2 years.ResultsAnalysis of 142 variables from 1,443 patients identified 41 PCs that accounted for 77% of the cumulative variance in the data set. Cluster analysis distinguished 5 patient clusters: 1) less RA disease activity/multimorbidity, shorter RA duration, lower incidence of comorbidities; 2) less RA disease activity/multimorbidity, longer RA duration, more infections, psychiatric comorbidities, health care utilization; 3) moderate RA disease activity/multimorbidity, more neurologic comorbidity; 4) more RA disease activity/multimorbidity, shorter RA duration, more metabolic comorbidity, higher body mass index; 5) more RA disease activity/multimorbidity, longer RA duration, more hepatic, orthopedic comorbidity and RA‐related surgeries. The clusters exhibited differences in clinical outcomes over 2 years of follow‐up.ConclusionData‐driven analysis of the BRASS registry identified 5 distinct phenotypes of RA. These results illustrate the potential of data‐driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent data set is ongoing.

Investigating the impact of disease and health record duration on the eMERGE algorithm for rheumatoid arthritis.

The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration. Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC). The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases. eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases.

Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis.

IntroductionNo published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data.MethodsThis observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models.ResultsPatients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX.ConclusionsIn clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX.FundingPfizer IncElectronic supplementary materialThe online version of this article (10.1007/s40744-019-00177-4) contains supplementary material, which is available to authorized users.

Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of...

SAT0599 EXPLORING HETEROGENEITY IN RHEUMATOID ARTHRITIS: OUTCOMES UP TO 4 YEARS OF FOLLOW-UP IN PATIENT CLUSTERS IDENTIFIED BY DATA-DRIVEN ANALYSIS OF THE BRASS REGISTRY

Background: Patients with rheumatoid arthritis (RA) may share characteristics that relate to their future outcomes. Objectives: To investigate clinical outcomes over a 4-year follow-up period in objectively identified RA patient clusters derived empirically via a data-driven approach using the BRASS registry. Methods: Patient clusters were identified by principal components (PC) and cluster analysis of demographic, socio-economic, health and disease characteristics of patients on entry (baseline) into the BRASS registry. Patients in BRASS are followed in the clinic at least annually and are sent questionnaires at 6-month intervals. Mean score was calculated at 12- and 24-months follow-up as observed for Clinical Disease Activity Index (CDAI), Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), BRASS self-administered Rheumatoid Arthritis Disease Activity Index (RADAI), swollen and tender joint count (SJC and TJC), Multidimensional Health Assessment Questionnaire (MDHAQ), and Functional Status Mental Health Index (FSMHI). Time to first infection and to first RA medication change over 4 years was analysed via Kaplan-Meier curves. Results: PC analysis of variables among 1443 patients recorded at entry into BRASS identified 41 PCs that capture the fundamental characteristics involved in RA. These PCs informed the identification of 5 novel patient clusters. Cluster 1 patients (“health low, RA uncontrolled, shorter RA duration”) exhibited the greatest reduction in TJC. Cluster 2 patients (“health high, RA controlled, shorter RA duration”) remained free of infection longer than other clusters. Cluster 3 patients (“health high, RA controlled, longer RA duration”) sustained the lowest mean SJC throughout follow-up. Cluster 4 patients (“health low–moderate, moderate RA”) exhibited the greatest improvement in mental health (FSMHI; Figure). Cluster 5 patients (“health low, RA uncontrolled, longer RA duration”) exhibited the highest CDAI scores (Figure) and maintained baseline line of therapy the longest. Conclusion: Five patient clusters identified by data-driven PC analysis of the BRASS registry exhibited distinct patterns of clinical outcome and management over a 4-year follow-up period. The clinical outcomes data suggest the clusters represent clinically meaningful categories of RA and illustrate the potential of data-driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent dataset is ongoing. Acknowledgement: Study funding and medical writing support (Matt Lewis, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interests: Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Kenneth Saag Grant/research support from: Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda, Consultant for: Abbvie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Christina Charles-Schoeman Grant/research support from: Bristol-Myers Squibb, AbbVie, and Pfizer, Consultant for: Regeneron-Sanofi, Pfizer, and Gilead, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Gregory St. John Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Toshio Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Shen Zheng Consultant for: Sanofi, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Grace Wright Consultant for: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Pfizer, Sanofi Genzyme Regeneron, UCB, Speakers bureau: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Sanofi Genzyme Regeneron, UCB, Martin Bergman Shareholder of: Johnson and Johnson (parent company of Janssen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Kamala Nola Shareholder of: Gilead, Johnson & Johnson, Proctor & Gamble, Consultant for: Yes – Gilead, Sanofi Genzyme, Regeneron, Speakers bureau: Coherus, Daniel E. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS Corbus, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron.

Influence of disease duration and socioeconomic factors on the prevalence of infection and hospitalization in rheumatoid arthritis: KRAC study.

The use of healthcare resources by rheumatoid arthritis (RA) patients can be related to the presence of disease, comorbid conditions, use of steroids, and the combined use of immunosuppressants. This study evaluated the risk factors associated with infection and hospitalization in RA. This multicenter, cross-sectional study enrolled 3247 RA subjects fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria to examine the prevalence of hospitalization and episodes of documentable non-tubercular infections as a part of the "Karnataka rheumatoid arthritis comorbidity" study (KRAC). The study included 2081 subjects and 1166 were excluded due to incomplete data. Demographic, clinical and treatment variables were collected, and the events related to infections and hospitalization were extracted from the medical records. Comparative analysis and multivariate logistic regression were performed. Around 22% of the subjects had hospitalizations and 2.9% had infections. Infections were pertaining to dental (1.3%), urinary tract (1.6%) and candidiasis (0.2%). Skin- and soft tissue-related infections were found in 1.8% and 0.3% of patients, respectively. Increased need of hospitalization in RA patients was associated with advanced age (≥60years), lower education, family income, and longer duration of RA. Presence of comorbidity, usage of three or more disease-modifying anti-rheumatic drugs (DMARDs) and family income influenced the likelihood of infection. Dental infections were less likely in working subjects and more likely in patients with increased disease duration, higher family income, comorbidities and those between the age group 40-59years. Urinary tract infection was associated with DMARD usage. Patient-specific risk factors should be considered to improve treatment strategies and to reduce the risk of infection and hospitalization in RA patients.

Prevalence of Subclinical Amyloidosis in a Cross-sectional Study of Egyptian RA Patients without Proteinuria.

Amyloidosis is a life-threatening complication of Rheumatoid Arthritis (RA) that should be detected as early as possible to avoid its morbidity and mortality. To detect subclinical amyloidosis in RA patients without proteinuria and a disease duration more than 5 years. Eighty-six RA patients seen between October 2013 and August 2014 were recruited for the study. Those with 5 years disease duration were included in the study but those who had proteinuria, serum creatinine > 1.5 mg/dl, disease onset before the age of 16 years or improper specimens, were excluded, leaving 30 eligible patients (23 women, 7 men). The clinical, laboratory and imaging results and treatments were maintained for each patient. Abdominal Fat Aspiration Biopsy (AFAB) was performed on all 30 patients. Amyloid deposits were spotted by polarised light microscopy following Congo red staining. Informed consent was acquired from all patients. Clinical disease activity was scored according to DAS. ELISA measured serum amyloid A protein (SAA), CRP and RF. AFAB stained positive for amyloid in 4 (13.3%) patients out of 30. The amyloid deposits were (1+) in 1 patient and (2+) in 3 patients. Longer RA duration correlated positively with amyloidosis (12.50 years versus 6.15years) (P < 0.001). Extra-articular manifestations were present in 50% of the amyloid patients and in 15.3% of the non-amyloid patients. This difference was significant (P < 0.01). DAS 28 score was higher in amyloid patients (P < 0.001). No difference was found between amyloid and non-amyloid patients regarding age, sex or deformities. SAA was significantly higher in amyloid patients (P < 0.001). However, haemoglobin levels were found to be significantly lower in amyloid patients (P < 0.001). The prevalence of subclinical amyloidosis by AFAB was found to be (13.3%). The use of AFAB should be encouraged, particularly in patients with longer disease duration and low haemoglobin level to confirm early detection of subclinical amyloidosis.

Serum Complement C3 and Type 2 Diabetes in Rheumatoid Arthritis: A Case-Control Study.

Recent evidence demonstrated a potential role of complement C3 as a candidate biomarker of cardiometabolic risk in the general population. Aim of the present study was to investigate the correlation between complement C3 levels and comorbid Type 2 Diabetes (T2DM) in Rheumatoid Arthritis (RA) patients. For the present study, 40 consecutive diabetic RA patients (RA/T2DM+ group) and 80 consecutive RA patients without diabetes (RA/T2DM- group) were recruited. Patients in the RA/T2DM+ group were significantly older (p < 0.0001), had a longer RA duration (p < 0.0001) and higher disease activity (p = 0.006) compared to controls. Moreover, patients in the RA/T2DM+ group had significantly higher levels of ESR (p < 0.0001), CRP (p < 0.0001) and complement C3 (p < 0.0001). A logistic regression model was built to ascertain the effect of selected variables (age, RA duration, BMI, ESR, C3, lnCRP, corticosteroid use) on the likelihood that patients have T2DM. Longer RA duration, ESR and C3 were associated with an increased likelihood of being classified as T2DM. Finally, we built ROC curves to evaluate the predictivity of RA duration, complement C3 and the combination of both variables on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.79 (p < 0.0001) for RA duration, 0.71 (p < 0.0001) for complement C3 and 0.89 (p < 0.0001) for the combination of both variables. According to our data complement C3 levels can predict the presence of T2DM in RA patients.