The first involved joints and associated factors in patients with rheumatoid arthritis.

Objectives: This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). Patients and methods: This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Results: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. Conclusion: The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.

At Early Rheumatoid Arthritis Stage, the Infectious Spectrum Is Driven by Non-Familial Factors and Anti-CCP Immunization.

Background/Objectives: Patients with rheumatoid arthritis (RA) are prone to develop infections. Methods: Accordingly, 195 untreated early (e)RA patients and 398 healthy controls were selected from women in Tatarstan's cohort to study infectious history in the anamnesis (four criteria) and in the previous year (16 criteria). Information about annual infections was collected face-to-face from year to year by a qualified rheumatologist/general practitioner and included the active use of information from medical records. Results: In the anamnesis, tuberculosis, and pneumonia, and in the previous year, respiratory tract infections, skin infections, and herpes simplex virus reactivation incidence were reported to be increased in eRA patients, as well as the event number and duration of acute and chronic tonsillitis. Moreover, more bacterial-suspected upper respiratory infections and urinary tract infections were retrieved in sporadic eRA patients as compared to familial eRA patients. An elevated immunization against CCP prevented respiratory tract infection in those with HSV exacerbation. Finally, associations were retrieved between infection (event number/delay) and RA indices: (i) chronic tonsillitis exacerbations with disease activity and health assessment (HAQ) in familial eRA; (ii) bacterial-suspected upper respiratory infections with the number of swollen and tender joints in sporadic eRA; and (iii) HSV exacerbation with inflammation in eRA patients with negative/low response against CCP. Here, we demonstrate the complex nature of the interplay of RA with specific infections. Conclusions: For the first time, differences in the patterns of annual trivial infections and their links with RA indices were found in cohorts of familial and sporadic cases of the disease. Additionally, for the first time, we identified a remarkable relationship between early RA and exacerbations of chronic tonsillitis, as well as tuberculosis in the patient's history. Altogether, this study supports the existence of a complex interplay between infections and RA at onset driven by familial status and the presence of anti-CCP Ab at elevated levels.

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

BACKGROUND: Involvement 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. METHODS: Seventy-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. RESULTS: Compared 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). CONCLUSIONS: Cartilage 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.

Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past 17 years: Analyses from the IORRA cohort.

OBJECTIVES: The aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years. METHODS: Japanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001-06) and B (2007-12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated. RESULTS: Groups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59-1.08) and 0.78 (0.57-1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68-1.19) for Group A and 0.92 (0.68-1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively. CONCLUSIONS: The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Role of IFN-α in Rheumatoid Arthritis.

PURPOSE OF REVIEW: Type 1 interferons (IFN-I) are of increasing interest across a wide range of autoimmune rheumatic diseases. Historically, research into their role in rheumatoid arthritis (RA) has been relatively neglected, but recent work continues to highlight a potential contribution to RA pathophysiology. RECENT FINDINGS: We emphasise the importance of disease stage when examining IFN-I in RA and provide an overview on how IFN-I may have a direct role on a variety of relevant cellular functions. We explore how clinical trajectory may be influenced by increased IFN-I signalling, and also, the limitations of scores composed of interferon response genes. Relevant environmental triggers and inheritable RA genetic risk relating to IFN-I signalling are explored with emphasis on intriguing data potentially linking IFN-I exposure, epigenetic changes, and disease relevant processes. Whilst these data cumulatively illustrate a likely role for IFN-I in RA, they also highlight the knowledge gaps, particularly in populations at risk for RA, and suggest directions for future research to both better understand IFN-I biology and inform targeted therapeutic strategies.

A serum metabolic biomarker panel for early rheumatoid arthritis.

Objective: There is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA. Methods: We applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel. Results: Significant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA. Conclusion: A metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA.

Long-term fracture risk in rheumatoid arthritis: impact of early sustained DAS28-remission and restored function, progressive erosive disease, body mass index, autoantibody positivity and glucocorticoids. A cohort study over 10 years.

BACKGROUND: Risk of fragility fractures in patients with rheumatoid arthritis (RA) is increased. Disease-related inflammation in RA is associated with low Bone Mineral Density (BMD). However, effects of specific disease factors on fracture occurrence and whether or not such disease effects are independent of BMD are unknown. METHODS: Analysis of fracture outcome in the prospective cohort of 2557 patients with early RA (67% women, mean age 58.1 ± 15.6 years) during an observation period of 10.6 ± 4.7 years. In 602 patients BMD was measured at baseline. The first major fragility fractures were considered. Kaplan-Meier and Cox regression analysis, adjusted for traditional factors, prior fracture, disease activity and period of inclusion, were used to estimate the risk of the outcome. RESULTS: During follow-up fracture occurred in 352 patients (13.8%), a rate of 13/1000 p-y. A proportional risk reduction for the outcome was associated with Body Mass Index (BMI) at baseline, BMI ≥ 30 kg/m2, and over the first two years sustained Disease Activity Score (DAS28)-remission, DAS28-low disease activity and Health Assessment Questionnaire (HAQ) ≤ 0.5. The proportional risk elevation for fractures was associated with BMI ≤ 20 kg/m2, DAS28 at baseline, 6-month and at 1-year, cumulative DAS28 over the two years, RF, erosion score progression at 2-year, HAQ score and HAQ ≥ 1 at 6-month and 1-year and showed a trend for ACPA positivity. The estimated fracture risk was increased in users of glucocorticoids (GC), associated with a higher GC-dosage at follow-ups and a higher cumulative dosage over two years, independently of disease activity. With adjustment for BMD, there was no difference in fracture outcome by exposure to GC. The effects of a higher BMI, DAS28-remission and low HAQ ≤ 0.5 attained at 6-month of treatment initiation and sustained up to 2 years, RF, ACPA, and erosion score progression at 2-year were independent of low BMD. CONCLUSIONS: This analysis supports importance of RA-specific risk factors in early RA for future major fragility fractures. Treat-to-target strategy and restored functional capacity in early RA-disease are important to prevent fractures. Autoantibody positivity, progressively erosive disease, and low weight could have additional value for personalized fracture preventive strategies in early RA.

Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?

Background: Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect. Aim: The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group. The study was conducted because previous results have been insufficient. Methods: The study group consisted of 83 ERA patients and 321 control subjects. A dual-energy X-Ray absorptiometry (DXA) machine was used to measure hip, lumbar spine, and radius BMD, as well as arm and leg fat, lean, and bone mass. Dietary habits and inflammatory markers were assessed to evaluate the effects to BMD and limb structural changes. Results: In ERA subjects, higher dietary consumption of PUFAs was associated with a decrease in arm fat mass (b -28.17, P = .02) and possibly with higher lumbar BMD (b 0.008, P = .058). Limb bone and lean mass changes were not associated with dietary intake of PUFAs. Conclusion: Balanced nutrition is essential. Consuming PUFAs could be beneficial in ERA preventing structural changes to hands, but additional research is needed.

New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis.

OBJECTIVE: Interleukin (IL)-40 is a new cytokine related to immune system function and malignancies. Recently, an association of IL-40 with rheumatoid arthritis (RA) and externalisation of neutrophil extracellular traps (NETosis) was found. As neutrophils are implicated in RA development, we investigated IL-40 in early stages of RA (ERA). METHODS: IL-40 was determined in serum of treatment naïve patients with ERA at baseline (n=60) and 3 months after initiation of conventional therapy and in healthy controls (HC; n=60). Levels of IL-40, cytokines and NETosis markers were measured by ELISA. NETosis was visualised by immunofluorescence. In vitro experiments were performed on peripheral blood neutrophils from ERA patients (n=14). Cell-free DNA was analysed in serum and supernatants. RESULTS: Serum IL-40 was elevated in ERA compared with HC (p<0.0001) and normalised after 3 months of therapy (p<0.0001). Baseline serum IL-40 correlated with rheumatoid factor (IgM) (p<0.01), anti-cyclic citrullinated peptide (p<0.01) autoantibodies and NETosis markers (proteinase 3; neutrophil elastase (NE); myeloperoxidase) (p<0.0001). Levels of NE significantly decreased after therapy (p<0.01) and correlated with the decrease of serum IL-40 (p<0.05). In vitro, neutrophils enhanced IL-40 secretion following NETosis induction (p<0.001) or after exposure to IL-1ß, IL-8 (p<0.05), tumour necrosis factor or lipopolysaccharide (p<0.01). Recombinant IL-40 up-regulated IL-1ß, IL-6 and IL-8 (p<0.05 for all) in vitro. CONCLUSION: We showed that IL-40 is significantly up-regulated in seropositive ERA and decreases after conventional therapy. Moreover, neutrophils are an important source of IL-40 in RA, and its release is potentiated by cytokines and NETosis. Thus, IL-40 may play a role in ERA.

Stratified distribution of Th17 and Treg cells in patients with multi-stage rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a typical, progressive autoimmune disease. Its occurrence and development are associated with dysregulation of T and B cell numbers. However, the specific immune characteristics of different RA courses remain incompletely defined. Here, we describe the peripheral blood lymphocyte subsets, particularly CD4 + T subsets, of different RA courses with a focus on early RA (Ea-RA). METHODS: In all, 131 patients with Ea-RA, 117 with advanced RA (Ad-RA), and 109 with treated RA (Tr-RA) were enrolled. We collected general clinical data. Whole blood samples obtained from the patients and 97 healthy controls (HCs) were analysed via flow cytometry. RESULTS: Decreased absolute NK cell numbers and increased CD4/CD8 T cell ratios were observed in different RA groups, including Ea-RA, compared to healthy controls. In Ea-RA patients, the Th17 and Treg cell numbers were similar to those in HCs. We performed k-means clustering based on the profiles of Th17 and Treg cells for patients with multi-stage of RA. We identified three patient types: type A characterised by relatively low Treg and Th17 cell numbers, type B with moderate levels of Treg cells and levels of Th17 cells similar to that of type C patients, and type C with high levels of Treg cells and levels of Th17 cells similar to that of type B patients. CONCLUSION: The immune characteristics of Ea-RA patients differ from those of HCs; an immune system disorder is apparent although no differences in Th17 and Treg levels were evident between Ea-RA patients and HCs. We found distributional heterogeneities of Th17 and Treg cells in patients with multi-stage of RA. Stratified management based on such heterogeneity may serve as a useful novel immunotherapy allowing of early intervention.

Factors associated with hand bone changes in early rheumatoid arthritis.

BACKGROUND: The aim of this research was to assess if hand bone mineral density (HBMD) changes associated with the appearance of erosions in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we tried to identify if there are novel factors that associate with HBMD and erosive changes (EC), and if they are dissimilar. The study was conducted as the data are limited. METHODS: The study group consisted of 83 ERA patients and 321 controls. Dual-Energy X-Ray Absorptiometry (DXA) machine was used to measure HBMD. EC of RA (rheumatoid arthritis) were assessed in X-rays of hands using Sharp scores. Life-style habits, inflammation markers were assessed to evaluate the effects of different factors. RESULTS: The presence of ERA was associated with lower HBMD compared with controls (adjusted for age, gender, height and weight; b -0.01, p = 0.045). 76% (95% CI 65.3-84.6) of ERA patients had EC in hand X-ray. Smoking habits and higher BMI (body mass index) were associated with an increased likelihood of having RA specific EC. In ERA, decreasing of HBMD was associated with the elevation of interleukin-6 (IL-6) and rheumatoid factor (RF) positivity. CONCLUSIONS: In ERA, HBMD changes were not associated with the appearance of erosions. Factors that associate in ERA with HBMD changes and appearance of erosions differ. HBMD assessment together with serum IL-6 level could be useful in everyday clinical practice for better surveillance of ERA patients who do not have EC in hand X-rays.

Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis.

Background: Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. Methods: This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). Results: In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Conclusion: Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

Development of a patient-led clinic visit framework: a case study navigating a patient's journey for rheumatology outpatient clinic consultations in England and Wales.

BACKGROUND: Involving patients and members of the public in healthcare planning is beneficial for many reasons including that the outcomes focus on topics relevant to service users. The National Early Inflammatory Arthritis Audit (NEIAA) aims to improve care quality for patients with inflammatory arthritis. CASE STUDY: This paper presents a case study detailing how the NEIAA Patient Panel worked with NEIAA governance groups, the National Rheumatoid Arthritis Society and the National Axial Spondyloarthritis Society to co-create an outpatient clinic visit framework for rheumatology professionals. A framework was co-created, divided into nine sections: pre-appointment preparation, waiting area (face-to-face appointments), face-to-face consultations, physical examination, establishing a forward plan, post consultation, annual holistic reviews, virtual appointments and key considerations. Providing insight into how the multi-disciplinary team can meet the diverse needs of patients with inflammatory arthritis, this framework now informs the teaching content about people who live with physical and mental disability for Year 3 and 4 undergraduate medical students at King's College London. CONCLUSION: Patients play an important role in helping to address gaps in health service provision in England/Wales. The co-production of a clinic visit framework, informed by their own lived experience and their own expectations can lead to improved and relevant outcomes for the benefit of patients and raises awareness to medical students what matters to patients with physical disabilities when attending outpatient care.

Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study.

Objectives: To describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden. Methods: We performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity. Results: A total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%); p = 0.018] and high values for CRP (p = 0.039) and IL-6 (p = 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49-10.71); p = 0.008], smoking [OR (95% CI) 2.07 (1.13-3.78); p = 0.017], anti-citrullinated peptide antibody [OR (95% CI) 3.24 (1.15-9.13); p = 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03-14.23); p = 0.034], and physical activity [OR (95% CI) 0.99 (0.99-0.99); p = 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA. Conclusion: Control of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.

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

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

Rheumatoid Arthritis: Early Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder that manifests as a symmetric polyarthritis of small and large joints that may lead to joint and periarticular structural damage and the consequences of systemic inflammation. This overview of early RA examines the unmet needs and challenges in RA, how to best diagnose RA, and pitfalls in early diagnosis and treatment. The rules for referral to a rheumatologist are reviewed. Primary care physicians are at the front line of early diagnosis and need to start disease-modifying therapy as soon as a diagnosis of RA is established.

Study of Plasma Anti-CD26 Autoantibody Levels in a Cohort of Treatment-Naïve Early Arthritis Patients.

In rheumatoid arthritis (RA), the identification of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantification in plasmas from 106 treatment-naïve early and undifferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the first visit from patients, which were later classified as RA and non-RA according to the American College of Rheumatology criteria. Two different isotype signatures were found among ten groups of patients, one for Anti-CD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undifferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatment-naïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseases.

Clinical management and discontinuation of treatment in patients with recent onset rheumatoid arthritis in a rheumatology consultation.

INTRODUCTION: The treatment of Rheumatoid Arthritis (RA) has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early RA cohort in daily clinical practice, especially DMARD discontinuations and reasons. METHODS: A retrospective observational study of patients with RA diagnosed between 01/07 and 12/14 followed up to 01/17, using >1 DMARD ≥ 3 months. VARIABLES: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients*year with 95% confidence interval. RESULTS: 814 patients were included with 2388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially Methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly Etanercept). There were 1094 discontinuations (29.5 [27.8-31.3]). The DIR was higher for adverse events (15.9 [14.7-17.3]), biologicals (49.6 [43.1-57.2]) and combined therapy. The DMAR with the lowest DIR was MTX (25.8 [23.8-28.1]). CONCLUSION: Methotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29*100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. MTX is the drug with the lowest DIR.

Manejo clínico y discontinuación de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatología / Clinical Management and Discontinuation of Treatment in Patients with Recent Onset Rheumatoid Arthritis in a Rheumatology Consultation

Introducción: El tratamiento de la artritis reumatoide ha cambiado drásticamente en los últimos años, sobre todo con el uso de los fármacos modificadores de la enfermedad (FAME). Los datos sobre el manejo de esta enfermedad en ensayo clínico son abundantes, pero no en la vida real. El objetivo de nuestro estudio es describir el manejo de una cohorte de artritis reumatoide de inicio en práctica clínica diaria, especialmente las suspensiones de los FAME y sus causas. Métodos: Estudio observacional retrospectivo de pacientes con artritis reumatoide diagnosticados entre 01/07 y 12/14 seguidos hasta 01/17, que usaron>1 FAME≥3 meses. Variables: sociodemográficas, clínicas, tratamiento, suspensión del FAME y causa. Análisis descriptivo de las características sociodemográficas, clínicas y de tratamiento. Incidencia de suspensión (IS) por técnicas de supervivencia, expresándose en 100 pacientes/año con intervalo de confianza del 95%. Resultados: Se incluyen 814 pacientes con 2.388 cursos de tratamiento, el 77% mujeres, edad media 57,5 años. Primer curso: monoterapia (92,75%), especialmente metotrexate (56,06%). En posteriores cursos aumentan terapia combinada y uso de biológico (principalmente etanercept). Se registraron 1.094 suspensiones (29,5 [27,8-31,3]). La IS fue mayor para evento adverso (15,9 [14,7-17,3]), biológicos (49,6 [43,1-57,2]) y terapia combinada. El FAME con menor IS fue metotrexate (25,8 [23,8-28,1]). Conclusión: El metotrexate fue el fármaco más utilizado, el biológico aumentó a lo largo del seguimiento, siendo el más frecuente etanercept. La IS de los FAME fue 29/100 pacientes año, principalmente por evento adverso. Parece mayor en las terapias que incluyen biológicos y en las combinadas. El metotrexate es el fármaco con menor IS.(AU)

Introduction: The treatment of rheumatoid arthritis has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early rheumatoid arthritis cohort in daily clinical practice, especially DMARD discontinuations and reasons. Methods: A retrospective observational study of patients with rheumatoid arthritis diagnosed between 01/07 and 12/14 followed up to 01/17, using>1 DMARD≥3 months. Variables: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients/year with 95% confidence interval. Results: 814 patients were included with 2,388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly etanercept). There were 1,094 discontinuations (29.5 [27.8-31.3]). The DIR was higher for adverse events (15.9 [14.7-17.3]), biologicals (49.6 [43.1-57.2]) and combined therapy. The DMAR with the lowest DIR was methotrexate (25.8 [23.8-28.1]). Conclusion: Methotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29/100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. Methotrexate is the drug with the lowest DIR.(AU)