Long-term Outcome Of Rheumatoid Arthritis Research Articles

The Relationship of Inflammatory Chemokine, CXCL12, with NT-proBNP: A Marker of Congestive Heart Failure in Rheumatoid Arthritis Patients

Background: Cardiovascular disease (CVD) is the most considerable long-term outcome of rheumatoid arthritis (RA) and the leading cause of premature death in RA patients. The pathogenesis of CVD in RA is largely determined by persistent systemic inflammation and its underlying factors, including chemokines. In this regard, C-X-C motif chemokine ligand 12 (CXCL12) has a crucial role in the CVD and RA pathogenesis. For the first time, plasma CXCL12 was related to conventional CV risk and well-established cardiac biomarkers in RA patients. Methods: This study was conducted on 30 RA patients who have been newly diagnosed, 30 under-treatment RA patients, and 30 healthy subjects. The plasma levels of CXCL12 and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The high sensitivity C-reactive protein (HS-CRP) concentration was evaluated in plasma samples using the ADVIA 1800 Clinical Chemistry System based on the latex-enhanced immunoturbidimetric assay. The CVD risk was measured by calculating the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). Results: The mean FRS and plasma concentration of high-density lipid (HDL), NT-proBNP, and HS-CRP were significantly different between the three groups (P = 0.029, P < 0.001, P = 0.016, P < 0.001, respectively). A significant positive correlation was found between CXCL12 with disease activity score-28 (DAS-28) (P = 0.024, r = 0.293) and NT-proBNP (P < 0.0001, r = 0.570) in the patients’ group. Conclusions: Based on the results, there was a significant relationship between the inflammatory mediator CXCL12 and a well-known cardiac biomarker, NT-proBNP.

Do it fast! Early access to specialized care improved long-term outcomes in rheumatoid arthritis: data from the REAL multicenter observational study

BackgroundEarly rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions.MethodsAdults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed “early” when the rheumatologist was the first or second physician consulted after symptoms onset, and “late” when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student’s t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent.ResultsWe included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6–36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: -0.25 [-0.46, -0.04] and − 0.196 [-0.306, -0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample.ConclusionsEarly diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes.

Patient perspectives on long-term outcomes in rheumatoid arthritis. A qualitative study from the OMERACT patient outcomes in longitudinal studies working group

ObjectivesTo identify patient-centered domains with long-term relevance to people with rheumatoid arthritis (RA). MethodsWe conducted semi-structured individual cognitive interviews of patients with RA with at least five years of disease duration, sampled from five different countries (United States, Italy, Spain, Mexico, and Argentina). Participants were encouraged to discuss their long-term concerns regarding RA. Interviews were transcribed and analyzed using qualitative content analysis within a constructivist/interpretivist theoretical framework. ResultsTwenty-eight participants were interviewed, 24 were women. Six main themes, representing important aspects of the daily life of people with RA were generated: (i) Living with symptoms and functional limitations, (ii) Lack of participation, (iii) Partner and family issues, (iv) Risk of damage to vital organs, (v) Coping strategies, and (vi) Healthcare concerns, primarily expressed by participants from non-European countries lacking universal healthcare coverage. In addition, participants discussed the importance of contextual factors and how they impact long-term outcomes. These included attitudes towards disease, social support, or financial burdens. ConclusionsWe identified six domains of importance to people with RA that are seldom measured in longitudinal registries and should be considered in patient-centered longitudinal studies.

Implications of a diagnosis of rheumatoid arthritis in resource-poor countries.

Rheumatoid arthritis (RA) is a multisystemic autoimmune disease that predominantly affects synovial joints. It causes marked disability, reduces health-related quality of life, and leads to high mortality. The diagnosis of RA is often made by standard criteria, and the management of this condition is usually undertaken according to the established guidelines. In resource-poor settings, the diagnosis and management of RA are hampered by diverse factors such as late presentation, inadequate trained personnel, poor healthcare infrastructure, low socioeconomic status, poor access to both conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics, and a high burden of infectious diseases such as tuberculosis, hepatitis, and human immunodeficiency virus. There is a need to establish registries in these settings to provide adequate information on the pattern, medication, and long-term outcome of RA in resource-poor countries in order to provide a practical and evidence-based management guide for rheumatologists, which is appropriate for these settings.

Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

BackgroundThe long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity.MethodsWe included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups.ResultsWe identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA.ConclusionsIn clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review.

Over 60% of rheumatoid arthritis (RA) patients achieve a good response after 12 months of treatment when following the European league against rheumatism (EULAR) guidelines for treatment. However, almost half of patients still suffer from moderate to severe disease activity despite this. In addition, mental health problems may remain despite reduced measures of inflammation systemically and within joints. Depression is two times more common in RA patients than in the general population, and intriguingly a bi-directional relationship with RA has been shown in cross-sectional studies. Chronic inflammation impairs the physiological responses to stress including effective coping behaviours, resulting in depression, which leads to a worse long-term outcome in RA. In RA patients, the pain score is not always solely related to inflammatory arthritis and immunological disease activity by Bąk et al. (Patient Prefer Adherence 13:223–231, [1]). Non-inflammatory pain secondary to anxiety, depression, sleep disturbance and the psychosocial situation needs to be considered whilst fibromyalgia, mechanical pain and neuropathic pain can also contribute to overall pain scores by Chancay et al. (Women's Midlife Health 5:3, [2]). Hence, the UK National Institute for Health and Care Excellence (NICE) guideline for the management of RA included psychological interventions for fatigue, low mood and social well-being (NICE NG100, 2018) [3], and the NICE clinical guidelines (CG91) [4] suggest managing mental health and depression in chronic medical conditions to improve treatment outcomes. This is a narrative review of the impact of mental health on RA disease activity in terms of patient-reported outcomes (PROs).

Subclinical Treatment Targets in Rheumatology: Lessons from Randomized Clinical Trials in Rheumatoid Arthritis.

In treat-to-target strategies, choosing the correct target is fundamental to success. The target should be associated with future good outcomes for the patient. Most rheumatic diseases are characterized by inflammation, affecting different tissues depending on the condition. Low-grade, subclinical inflammation is by definition not apparent on clinical examination, but may have significant long-term consequences for the individual. It has thus been debated whether targeting subclinical inflammation would improve long-term outcomes in rheumatoid arthritis. The authors use rheumatoid arthritis as an example to describe and discuss the status of subclinical targets in treat-to-target strategies within rheumatology.

Early Targeted Combination Treatment With Conventional Synthetic Disease-Modifying Antirheumatic Drugs and Long-Term Outcomes in Rheumatoid Arthritis: Ten-Year Follow-Up Results of a Randomized Clinical Trial.

The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions. Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed. Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74). In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions.

Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on survival.

Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid arthritis (RA). Among participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD and cardiovascular disease (CVD) using administrative and registry data. Demographics, smoking status, RA characteristics including Disease Activity Score in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were obtained from registry data, which were linked to the National Death Index to obtain vital status. We evaluated associations of CLD with survival using the multivariable Cox regression models. Among a large (n = 2053), male-predominant (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased 1.51-fold (95% CI 1.26-1.81) in RA patients with CLD after multivariable adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46 [1.03-2.06]; CVD alone 1.62 [1.35-1.94]). Survival was significantly reduced in those with interstitial lung disease (ILD) as well as other forms of CLD. Mortality risk with methotrexate and biologic use was not different in those with CLD compared to those without (p interaction ≥ 0.15) using multiple exposure definitions and propensity score adjustment. Mortality risk is significantly increased in RA patients with CLD. This risk is attributable not only to ILD but also to other chronic lung conditions and does not appear to be substantially greater in those receiving methotrexate or biologic therapies. Comorbid lung disease should be targeted as a means of improving long-term outcomes in RA.

Temporal trends in prevalence, incidence, and mortality for rheumatoid arthritis in Quebec, Canada: a population-based study.

Health administrative data are a potentially efficient resource to conduct population-based research and surveillance, including trends in incidence and mortality over time. Our objective was to explore time trends in incidence and mortality for rheumatoid arthritis (RA), as well as estimating period prevalence. Our RA case definition was based on one or more hospitalizations with a RA diagnosis code, or three or more RA physician-billing codes, over 2years, with at least one RA billing code by a rheumatologist, orthopedic surgeon, or internist. To identify incident cases, a "run-in" period of 5years (1996-2000) was used to exclude prevalent cases. Crude age and sex-specific incidence rates were calculated (using data from 2001 to 2015), and sex-specific incidence rates were also standardized to the 2001 age structure of the Quebec population. We linked the RA cohort (both prevalent and incident patients) to the vital statistics registry, and standardized mortality rate ratios were generated. Negative binomial regression was used to test for linear change in standardized incidence rates and mortality ratios. The linear trends in standardized incidence rates did not show significant change over the study period. Mortality in RA was significantly higher than the general population and this remained true throughout the study period. Our prevalence estimate suggested 0.8% of the Quebec population may be affected by RA. RA incidence appeared relatively stable, and mortality was substantially higher in RA versus the general population and remained so over the study period. This suggests the need to optimize long-term RA outcomes.

Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms

ObjectiveDisease-modifying antirheumatic drug (DMARD)-free sustained remission, the sustained absence of synovitis after cessation of DMARD therapy, is a relevant long-term outcome of rheumatoid arthritis (RA) if (1) its occurrence is...

Predictors of longterm changes in body mass index in rheumatoid arthritis.

Low body mass index (BMI) is a risk factor for poor longterm outcomes in rheumatoid arthritis (RA). The purpose of this study was to identify factors associated with longterm changes in BMI. Subjects with RA from the Veterans Affairs (VA) Rheumatoid Arthritis (VARA) Registry (n = 1474) were studied. Information on inflammatory markers, presence of erosions, and smoking status were extracted from the VARA database. BMI was extracted from VA electronic medical records within 14 days of each visit date. VA pharmacy records were queried to identify prescriptions for specific RA therapies within 1 month of the visit date. We used robust generalized estimating equations marginal regression models to calculate independent associations between clinical variables and BMI over time. Similar models determined predictors of change in weight and risk of weight loss over the subsequent study observation period. Increasing age, active smoking, and the presence of erosions at baseline were associated with lower BMI. Weight decreased over time among older adults. Factors associated with greater reductions in BMI over time and a greater risk of weight loss were higher inflammatory markers, smoking, older age, higher BMI, and less subsequent improvement in inflammation. Methotrexate use was associated with a lower risk of weight loss. The use of prednisone or anti-tumor necrosis factor therapies was not associated with change in BMI or the risk of weight loss independent of other factors. Greater age, greater inflammatory activity, and active smoking are associated with greater weight loss in RA over time.

AB0297 Does Delay of Therapy Affect Outcomes of Early RA in A T2T Clinic?

BackgroundVery early referral/start of therapy within 3-4 months vs. delayed referral has been shown beneficial for short- and long-term outcomes in rheumatoid arthritis (RA). However, treatment strategy in these studies...

Is a Patient Questionnaire Without a Joint Examination as Undesirable as a Joint Examination Without a Patient Questionnaire?

Patient questionnaires have gained increasing prominence in the treatment of rheumatic diseases over the last few decades. Three patient self-report scores for physical function, pain, and patient global estimate are included in the rheumatoid arthritis (RA) core dataset1. These 3 scores distinguish active from control treatments in RA clinical trials involving leflunomide2, methotrexate2, anakinra3, adalimumab4, abatacept5, and certolizumab6, at levels of significance similar to formal joint counts or laboratory tests. Patient physical function scores generally are more significant than radiographic scores or laboratory test results in the prognosis of severe longterm RA outcomes such as work disability and premature mortality7,8,9,10. Routine Assessment of Patient Index Data (RAPID3), an index of only the 3 patient-reported RA Core Data Set measures, is correlated significantly with standard indices that require a formal joint count, such as DAS28 (28-joint Disease Activity Score) and CDAI (Clinical Disease Activity Index)11,12. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints, RAPID3≤3+≤SJ1, provides remission criteria comparable to Boolean13, SDAI (Simplified Disease Activity Index), CDAI, and DAS2814 criteria in far less time than a formal joint count, in studies of the French ESPOIR early arthritis cohort15 … Address correspondence to Dr. Pincus, Division of Rheumatology, NYU Hospital for Joint Diseases, 301 East 17th St., Room 1608, New York, New York 10003, USA. E-mail: tedpincus{at}gmail.com

Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

IntroductionIt remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA.MethodsA cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2.ResultsA profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure.ConclusionsA profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA.

OP0183 Long-Term Outcome of Rheumatoid Arthritis Defined According to the 2010-Classification Criteria

BackgroundThe 2010 ACR/EULAR-criteria for RA have been thoroughly studied for the test characteristic but it is unclear whether ‘2010-RA’ has a different phenotype than ‘1987-RA’ when assessing the severity of...

FRI0487-HPR Dilemmas of participation in everyday life in early rheumatoid arthritis (RA), a qualitative interview study (the swedish TIRA study)

BackgroundAn important perspective in research is the patients’ own experiences of how it is to live with RA, in terms of dilemmas and consequences in everyday life. Although there have...

OP0051 Joint damage progression in established rheumatoid arthritis: Common and strongly associated with seropositivity

BackgroundDuring the last decade, rheumatoid arthritis (RA) research has mainly focused on early disease, as it has become apparent that early and aggressive treatment can change the long-term outcome of...

AB0225 Recruitment difficulty for unaffected rheumatoid arthritis relatives due to misplaced guilt ?

BackgroundProspective studies are needed to answer key questions on rheumatoid arthritis (RA) screening in at risk populations: 1. Is it possible to identify persons who will later develop RA? 2....

Long-term outcome of Rheumatoid Arthritis defined according to the 2010-classification criteria

ObjectiveThe 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been thoroughly studied for the test characteristics but it is unclear whether ‘2010 RA’...