Comparison between 2D FSE T2-weighted Dixon MRI and contrast-enhanced 2D FSE and 3D FSPGR T1-weighted Dixon MRI to quantify inflammation in hands of patients with early rheumatoid arthritis.

PURPOSE: The purpose of this study was to compare two-dimensional (2D) T2-weighted, contrast-enhanced 2D T1-weighted and contrast-enhanced three-dimensional (3D) T1-weighted Dixon MRI sequences to assess disease activity using the RAMRIS scoring system in hands of patients with early rheumatoid arthritis. MATERIALS AND METHODS: Twenty-five patients (19 women, 6 men; mean age 51.4 years ± 12.7 years [SD], age range: 28-70 years) with rheumatoid arthritis prospectively underwent MRI examination of both hands at 1.5 T using 2D fast spin-echo (FSE) T2-weighted, contrast-enhanced 2D FSE T1-weighted and contrast-enhanced 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon sequences. Three radiologists independently assessed disease activity according to RAMRIS using Dixon water-only and fat-only images. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique and interobserver agreements. RESULTS: Agreement to assess total RAMRIS score was very good between the MRI protocols (mean ICC ranging from 0.81 to 0.93) and between readers (mean ICC ranging from 0.91 to 0.94). Mean total RAMRIS scores of the three readers were significantly greater with contrast-enhanced 3D FSPGR T1-weighted (42.73 ± 29.39) than with contrast-enhanced 2D FSE T1-weighted (35.81 ± 25.48) and 2D FSE T2-weighted (32.20 ± 25.06) Dixon sequences. CONCLUSION: 2D FSE T2-weighted, contrast-enhanced 2D FSE T1-weighted Dixon and contrast-enhanced 3D FSPGR T1-weighted Dixon protocols are reproducible alternatives for the RAMRIS scoring in hands of patients with early rheumatoid arthritis. Coupling contrast-enhanced 3D FSPGR T1-weighted and 2D FSE T2-weighted sequences might be the most efficient option to completely assess the rheumatoid arthritis -related synovial and bone changes with the Dixon method.

Proteomic Approaches to Defining Remission and the Risk of Relapse in Rheumatoid Arthritis.

Objectives: Patients with Rheumatoid Arthritis (RA) are increasingly achieving stable disease remission, yet the mechanisms that govern ongoing clinical disease and subsequent risk of future flare are not well understood. We sought to identify serum proteomic alterations that dictate clinically important features of stable RA, and couple broad-based proteomics with machine learning to predict future flare. Methods: We studied baseline serum samples from a cohort of stable RA patients (RETRO, n = 130) in clinical remission (DAS28<2.6) and quantified 1307 serum proteins using the SOMAscan platform. Unsupervised hierarchical clustering and supervised classification were applied to identify proteomic-driven clusters and model biomarkers that were associated with future disease flare after 12 months of follow-up and RA medication withdrawal. Network analysis was used to define pathways that were enriched in proteomic datasets. Results: We defined 4 proteomic clusters, with one cluster (Cluster 4) displaying a lower mean DAS28 score (p = 0.03), with DAS28 associating with humoral immune responses and complement activation. Clustering did not clearly predict future risk of flare, however an XGboost machine learning algorithm classified patients who relapsed with an AUC (area under the receiver operating characteristic curve) of 0.80 using only baseline serum proteomics. Conclusions: The serum proteome provides a rich dataset to understand stable RA and its clinical heterogeneity. Combining proteomics and machine learning may enable prediction of future RA disease flare in patients with RA who aim to withdrawal therapy.

Integrative Clinical, Molecular, and Computational Analysis Identify Novel Biomarkers and Differential Profiles of Anti-TNF Response in Rheumatoid Arthritis.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients. Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions. Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort. Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

The accuracy of administrative health data for identifying patients with rheumatoid arthritis: a retrospective validation study using medical records in Western Australia.

The use of administrative health datasets is increasingly important for research on disease trends and outcome. The Western Australian (WA) Rheumatic Disease Epidemiological Registry contains longitudinal health data for over 10,000 patients with rheumatoid arthritis (RA). Accurate coding for RA is essential to the validity of this dataset. Investigate the diagnostic accuracy of International Classification of Diseases (ICD)-based discharge codes for RA at WA's largest tertiary hospital. Medical records for a sample of randomly selected patients with ICD-10 codes (M05.00-M06.99) in the hospital discharge database between 2008 and 2020 were retrospectively reviewed. Rheumatologist-reported diagnoses and ACR/EULAR classification criteria were used as reference standards to determine accuracy measures. Medical chart review was completed for 87 patients (mean (± SD) age 64.7 ± 17.2 years), 67.8% female). A total of 80 (91.9%) patients had specialist confirmed RA diagnosis, while seven patients (8%) had alternate clinical diagnoses. Among 87 patients, 69 patients (79.3%) were fulfilled ACR/EULAR classification criteria. The agreement between the reference standards was moderate (Kappa 0.41). Based on rheumatologist-reported diagnoses and ACR/EULAR classification criteria, primary diagnostic codes for RA alone had a sensitivity of (90% vs 89.8%), and PPV (90.9% vs 63.6%), respectively. A combination of a diagnostic RA code with biologic infusion codes in two or more codes increased the PPV to 97.9%. Hospital discharge diagnostic codes in WA identify RA patients with a high degree of accuracy. Combining a primary diagnostic code for RA with biological infusion codes can further increase the PPV.

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study.

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.

Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis.

Despite nearly three decades of advances in the management of rheumatoid arthritis (RA), a substantial minority of patients are exposed to multiple DMARDs without necessarily benefitting from them; a group of patients variously designated as having 'difficult to treat', 'treatment-resistant' or 'refractory' RA. This Review of refractory RA focuses on two types of patients: those for whom multiple targeted therapies lack efficacy and who have persistent inflammatory pathology, which we designate as persistent inflammatory refractory RA (PIRRA); and those with supposed refractory RA who have continued disease activity that is predominantly independent of objective evidence of inflammation, which we designate as non-inflammatory refractory RA (NIRRA). These two types of disease are not mutually exclusive, but identifying those individuals with predominant PIRRA or NIRRA is important, as it informs distinct treatment and management approaches. This Review outlines the clinical differences between PIRRA and NIRRA, the genetic and epigenetic mechanisms and immune pathways that might contribute to the immunopathogenesis of recalcitrant synovitis in PIRRA, and a possible basis for non-inflammatory symptomatology in NIRRA. Future approaches towards the definition of refractory RA and the application of single-cell and integrated omics technologies to the identification of refractory RA endotypes are also discussed.

Improved classification of rheumatoid arthritis with a score including anti-acetylated ornithine antibodies.

The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance.

The Prevalence of Sjögren's Syndrome in Rheumatoid Arthritis Patients and Their Clinical Features.

BACKGROUND: To estimate the prevalence of Sjögren's syndrome (SS) in patients with rheumatoid arthritis (RA) and to compare the clinical features of RA patients with and without SS. METHODS: We conducted a retrospective study of RA patients who visited a rheumatology clinic in a tertiary referral hospital in Korea between May 20 and July 22, 2016. All patients fulfilled the classification criteria for RA, and the diagnosis of SS was made clinically by rheumatologists and according to the 2002 American-European Consensus Group (AECG), 2012 American College of Rheumatology (ACR), and 2016 ACR/European League Against Rheumatism (EULAR) classification criteria. The prevalence was estimated as the number of SS patients within the total number of RA patients. The disease activity and treatment pattern of RA were compared between patients with and without SS. RESULTS: Among 827 RA patients, 72 patients (8.7%) were diagnosed with SS by a rheumatologist, though only 60 patients (7.3%) satisfied the 2002 AECG classification criteria for SS. Fifty-two patients (6.3%) and 56 patients (6.8%) fulfilled the 2012 ACR and 2016 ACR/EULAR classification criteria, respectively. The prevalence of SS in RA patients was 10.5%, 17.0%, and 67.6% in rheumatoid factor, antinuclear antibody (≥ 1:80), and anti-Ro antibody positive patients, respectively. CONCLUSION: The prevalence of SS among RA patients was 8.7% according to rheumatologists' diagnosis. The presence of SS did not affect the treatment patterns of RA patients. However, the autoantibody profiles and demographics of RA patients with SS differed from those of patients without SS.

Cambio de diagnóstico y de categoría diagnóstica en pacientes con artritis idiopática juvenil en 7 años de seguimiento / Change of diagnosis and diagnostic category in patients with juvenile idiopathic arthritis within 7 years of follow-up

Resumen: Introducción: Al menos 50% de los pacientes pediátricos portadores de artritis idiopática juvenil (AIJ) continuará control en reumatología adulto. La clasificación de la Liga Internacional de Asociaciones de Reumatología (ILAR) vigente, actualmente en revisión, difiere de la clasificación de las artritis inflamatorias del adulto. Se ha reportado cambios de categoría en 10,8% de los pacientes durante el seguimiento. Objetivo: Analizar los pacientes con AIJ seguidos al menos 7 años para objetivar cambios de diagnós tico en la transición, e identificar factores de mal pronóstico funcional. Pacientes y Método: Estudio retrospectivo en base a registros clínicos. Se incluyó a la totalidad de los pacientes con AIJ controla dos en policlínico pediátrico del Hospital de Puerto Montt entre el año 2005 y 2017, que cumplieron siete o más años de seguimiento. Se realizó análisis descriptivo en base a variables clínicas: categoría diagnóstica, tiempo de evolución al diagnóstico, actividad clínica y serológica, y tiempo de evolución al inicio de la terapia farmacológica. Resultados: Se evaluaron 18 pacientes, 3 Oligo-articular (OA) persistente, 1 OA extendida, 4 Poli-articular (PA) factor reumatoide (FR) negativo, 4 PA FR positivo, 5 Sistémicas, 1 Psoriática, todos con seguimiento mayor a 7 años. Once de 18 niños fueron transfe ridos a adultos. Tres de 11 cambiaron de diagnóstico a Artritis Reumatoide (AR) más otra enferme dad autoinmune: Síndrome de Sjögren + Lupus eritematoso sistémico, Púrpura trombocitopénico inmune, Enfermedad autoinmune no clasificada y cinco de 11 niños de categoría ILAR: OA a Artritis reumatoide juvenil, OA extendida a PA FR negativo, 3 Sistémicas a PA FR negativo. Edad de inicio, formas poli-articulares, retrasos en diagnóstico y comienzo de terapia se asociaron a secuelas e infla mación persistente. Conclusiones: Ocho de once pacientes transferidos cambiaron denominación diagnóstica y/o presentaron otras enfermedades autoinmunes. Algunos factores de mal pronóstico deben mejorar.

Abstract: Introduction: At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up. Objective: To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis. Patients and Method: Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy. Results: We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation. Conclusions: Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.

Label-free detection of thalassemia and other ROS impairing diseases.

Pathogenesis of different diseases showed that some of them, especially thalassemia (T) and rheumatoid arthritis (RA) have an implicit association with oxidative stress and altered levels of reactive oxygen species (ROS). Introducing ROS level and the balance between ROS and antioxidants as essential metrics, an attempt was made to classify T and RA from normal individuals (treated as controls)(C) using synchronous fluorescence spectroscopy (SFS) and Raman line intensity of water. This non-invasive and label-free approach was backed up by a categorization algorithm that helped in the prediction of disease types from serum samples. The predictive system constituted principal component analysis (PCA) with four parameters, namely spectral intensity ratios of reduced nicotinamide adenine dinucleotide (NADH) to tryptophan (Trp) (NADH/Trp), kynurenine (Kyn) to tryptophan (Kyn/Trp), kynurenine to NADH (Kyn/NADH), and logarithmic changes in Raman line intensity of water (Rline), with the index headers containing the disease types. Rline has a positive correlation with both Kyn/Trp and Kyn/NADH and a negative correlation with NADH/Trp ratio, implying its direct or indirect association with oxidative stress. In addition to the classification of T, RA, and C a sub-classification of T into beta major and E-beta in their post and pre-splenectomized surgical stages could also be realized. Furthermore, receiver operating characteristic (ROC) analysis was deployed to ascertain that the misclassification error (ME) was negligible for the disease types. Graphical Abstract A schematic representation of the workflow converging into the categorical classification of disease classes.

A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: The concomitant presence of two autoimmune diseases - systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. METHODS: This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. RESULTS: A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE (p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort (p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. CONCLUSION: Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.

In search of pathobiological endotypes: a systems approach to early rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. Early referral and treatment are key to the effective management of the disease. This makes imperative the identification of biomarkers and of pathobiological endotypes. AREAS COVERED: This review describes recent efforts to integrate large-scale datasets for the identification of disease endotypes for precision medicine in early, seropositive RA. We conducted a search for systems and multi-omics papers in early RA patients through to 1 January 2020. We reviewed investigations of multiple technologies such as transcriptomic, proteomic and metabolomic platforms as well as extensive clinical datasets. We outline progress made and describe some of the advantages and limitations of current computational and statistical methods. EXPERT OPINION: The search for pathobiological endotypes in early RA is rapidly developing. While currently, studies tend to be small, reliant upon new technologies and unproven analytical tools, as the technology becomes cheaper and more reliable, and the properties of analytical tools for the integration of cross-platform biology become better understood, it seems likely that better biomarkers of disease, remission and response to individual therapies will emerge.

Predictive values of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in relation to serological aspects of the ACR/EULAR 2010 classification criteria for rheumatoid arthritis.

Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA.

[Change of diagnosis and diagnostic category in patients with juvenile idiopathic arthritis within 7 years of follow-up]. / Cambio de diagnóstico y de categoría diagnóstica en pacientes con artritis idiopática juvenil en 7 años de seguimiento.

INTRODUCTION: At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up. OBJECTIVE: To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis. PATIENTS AND METHOD: Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy. RESULTS: We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation. CONCLUSIONS: Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.

ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography.

The objective of this study is to assess the prevalence, localization, and severity of bone erosions on radiography (RX) and ultrasonography (US) according to ACPA status in patients with rheumatoid arthritis (RA). 78 patients with ACPA-positive (ACPA+) RA and 30 patients with ACPA-negative (ACPA-) RA fulfilling the ACR 1987 and/or ACR/EULAR 2010 criteria were consecutively included. On RX, a modified Sharp erosion score (SHSe) was evaluated by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). On US, erosions were scored on six bilateral joints (MCP2, 3, 5; MTP2, 3, 5) with a four-point scale to calculate the total US score for erosions (USSe). The mean total SHSe and USSe were 3.7 and 4.4 times higher in the ACPA+ group than in the ACPA- group, respectively (P < 0.001). On both RX and US, the most discriminating joint between the two groups was MTP5, especially in cases with bilateral erosion. Based on multivariate analyses, ACPA + status was associated with erosive RA on RX according to the EULAR 2013 definition criteria [OR 4.4 (95% CI 1.2-16.4)], and on US according to the following two definitions: the presence of at least two eroded joint facets [OR 3.7 (95% CI 1.4-9.9)] or at least one grade 2 joint facet erosion [OR 9.0 (95% CI 2.8-28.4)]. Compared to ACPA- RA, ACPA + RA is associated independently with more severe erosive disease on RX and US. Both US and RX bilateral erosions in MTP5 joints are highly discriminant for ACPA + RA patients (97.8% in US and 100% in RX).

Emerging intervention of antidepressant with DMARD in non-cancerous nociceptive persistent pain associated depression in FCA induced rheumatoid arthritic rats

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund's complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats

Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review.

Importance: Racial/ethnic minority groups, women, and elderly people experience a disproportionate burden of disease in rheumatoid arthritis (RA), making it particularly important to examine drug therapies in these populations. Despite a national health agenda to improve representation of diverse populations in randomized clinical trials (RCTs), there have been few large-scale analyses examining RCT demographic characteristics within rheumatology and none focusing on RA. Objective: To characterize the representation of racial/ethnic minority groups, women, and elderly people through a comprehensive systematic review of RA RCTs. Data Sources: A literature search of PubMed's MEDLINE database was conducted to identify RA RCTs in adults 19 years and older published in English between January 1, 2008, and January 1, 2018. Study Selection: Randomized double-blind RCTs examining any systemic, disease-modifying therapy were included. Secondary analyses of previously published RCTs were excluded. Of 1195 identified records, 240 articles (20.1%) met final selection criteria. The analysis focused on RCTs with at least 1 US-based site. Data Extraction and Synthesis: Data were extracted and synthesized according to the PRISMA guidelines for systematic reviews. Studies were screened for eligibility criteria. Demographic data on the age, sex, and race/ethnicity of RCT participants were extracted. Data analysis was conducted from October 25, 2018, to March 15, 2019. Main Outcomes and Measures: Representation of race/ethnicity and sex, defined as the proportion of total participants that belonged to each racial/ethnic group or sex. Trends in proportions over time were examined and compared with US demographic data. Results: A total of 240 RCTs with 77 071 participants were included. Of 126 RCTs with at least 1 US-based site (52.5%), the enrollment of minority racial/ethnic groups was significantly lower than their representation within the US Census population (16% vs 40%; P < .001), and the enrollment of men was significantly lower than the incidence of RA in men nationally (20.4% vs 28.6%; P < .001). There was no trend toward improved representation of racial/ethnic minority groups or men over time. Conclusions and Relevance: Given the disproportionate burden of RA among racial/ethnic minority groups, it is imperative that policy makers better incentivize the inclusion of racial/ethnic minority groups in RA RCTs.

Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC).

OBJECTIVE: To establish whether synovial pathobiology improves current clinical classification and prognostic algorithms in early inflammatory arthritis and identify predictors of subsequent biological therapy requirement. METHODS: 200 treatment-naïve patients with early arthritis were classified as fulfilling RA1987 American College of Rheumatology (ACR) criteria (RA1987) or as undifferentiated arthritis (UA) and patients with UA further classified into those fulfilling RA2010 ACR/European League Against Rheumatism (EULAR) criteria. Treatment requirements at 12 months (Conventional Synthetic Disease Modifying Antirheumatic Drugs (csDMARDs) vs biologics vs no-csDMARDs treatment) were determined. Synovial tissue was retrieved by minimally invasive, ultrasound-guided biopsy and underwent processing for immunohistochemical (IHC) and molecular characterisation. Samples were analysed for macrophage, plasma-cell and B-cells and T-cells markers, pathotype classification (lympho-myeloid, diffuse-myeloid or pauci-immune) by IHC and gene expression profiling by Nanostring. RESULTS: 128/200 patients were classified as RA1987, 25 as RA2010 and 47 as UA. Patients classified as RA1987 criteria had significantly higher levels of disease activity, histological synovitis, degree of immune cell infiltration and differential upregulation of genes involved in B and T cell activation/function compared with RA2010 or UA, which shared similar clinical and pathobiological features. At 12-month follow-up, a significantly higher proportion of patients classified as lympho-myeloid pathotype required biological therapy. Performance of a clinical prediction model for biological therapy requirement was improved by the integration of synovial pathobiological markers from 78.8% to 89%-90%. CONCLUSION: The capacity to refine early clinical classification criteria through synovial pathobiological markers offers the potential to predict disease outcome and stratify therapeutic intervention to patients most in need.