Undifferentiated Polyarthritis Research Articles

P046 A multinomial approach to prediction of methotrexate treatment response and discontinuation due to adverse events in rheumatoid arthritis

Abstract Background/Aims As recommended by the NICE guidelines, methotrexate (MTX) is typically prescribed as the first line therapy for patients with rheumatoid arthritis (RA). However, around 40% of patients do not respond to MTX at 6 months and around 80% experience adverse events (AEs). Our previous systematic review identified that clinical prediction models of MTX outcomes suffered from methodological limitations, including a lack of validation, suboptimal handling of missing data, and no consideration of competing risks, such as patients discontinuing due to adverse events (AEs). These shortcomings resulted in high risk of bias and should be addressed to aid the implementation of outcome prediction in clinical practice. Therefore, this study aimed to (i) develop a multinomial prediction model for estimating an individual’s risks of not achieving low disease activity (LDA) and discontinuing due to AEs at 6 months after starting MTX, using information observable at the starting point of treatment, (ii) update prognosis at 3 months, and (iii) internally validate these models to assess performance. Methods Data came from the national multi-centre (n = 38) Rheumatoid Arthritis Medication Study (RAMS), which recruited patients with a diagnosis of RA or undifferentiated polyarthritis starting MTX for the first time. We conducted a Patient and Public Involvement focus group with past and current MTX users, which informed our outcome choice of LDA (DAS28 ≤3.2). A multinomial logistic regression (MLR) was used to develop a prediction model that estimated the probabilities of three outcomes: 1) not in LDA, 2) achieved LDA, and 3) discontinued due to AEs. The updated model at 3 months was conditional on patients not having achieved LDA. Missing data was handled using multiple imputation and models were internally validated through bootstrapping. Calibration, discrimination, and variance explained was assessed to quantify model performance. Results A total of 1632 patients were included in the analysis. At 6 months, 756 (46%) patients achieved LDA, 730 (45%) were not in LDA, and 146 (9%) discontinued due to AEs. The updated model at 3 months included 1179 (72%) patients as they had not achieved LDA. For the LDA outcome pair, the c-statistic was 0.73 (0.70, 0.75), while it was 0.54 (0.49, 0.59) for the AEs outcome. The calibration slope was 0.99 (0.85, 1.12) and 0.74 (0.23, 1.23), respectively. Predictive performance at 3 months was similar to baseline. Conclusion Our MLR models handled outcomes of disease activity and AEs simultaneously. We were able to predict outcomes of LDA more accurately than AEs and performance was better in terms of calibration, which is crucial for the clinical utility of a prediction model. This modelling approach could provide more clinically useful and realistic predictions of MTX outcomes, as competing risks such as AEs have previously been ignored. Disclosure C.K. Gehringer: None. G.P. Martin: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; BMS and Pfizer. S.M.M. Verstappen: None. J.C. Sergeant: None.

Post-chikungunya arthritis: a longitudinal study in a tertiary care hospital in Bangladesh

Background and objectiveTo identify the clinical patterns and consequences of post-chikungunya arthritis was the study's objective.MethodsThis longitudinal study was carried out among 143 Chikungunya virus (CHIKV) infected adult patients at the rheumatology department, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, during the outbreak of CHIKV infection in 2017. The disease was categorized into three phases: acute or febrile (lasting up to 10 days), subacute (11–90 days), and chronic (> 90 days). Patients who progressed towards the chronic phase were followed up to 1-year. Post-CHIKV de novo chronic inflammatory rheumatisms (CIRs) were characterized by persistent mono or oligoarthritis, undifferentiated polyarthritis, or meet the criteria rheumatoid arthritis (RA) or Spondyloarthritis (SpA). In addition, functional status was assessed by the validated Bangla version of the Health Assessment Questionnaire (HAQ).ResultsMean age was 43.3 ± 11.5 years, and 51.0% were male. Within 1-year follow-up, 60 (41.9%) patients were suffering from arthralgia/ arthritis. Of them 52 patients did not have any pre-existing arthralgia/arthritis. 35 (65.3%) had undifferentiated arthritis, 10 (19.2%) had SpA, and 7 (13.5%) had RA. Patients with pre-existing rheumatological disorders, 6(4.2%) had SpA, 1(0.7%) had RA and 1(0.7%) had osteoarthritis. Polyarthralgia (n = 33, 55.0%) and polyarthritis (n = 20, 33.3%) were the main presentations. Female gender (OR: 0.45; CI: 0.21–0.96), positive IgG (OR: 0.30; CI: 0.12–0.76), and moderate to severe functional disability (OR: 3.46; CI: 1.62–7.40) were independent predictors of developing chronic post-CHIKV rheumatism.ConclusionsAt 1-year follow-up, more than one-third of the patients remained symptomatic. Female gender, positive IgG, and moderate to severe functional disability contributed to the development of chronicity.

Absence of metacarpophalangeal synovitis by high-resolution ultrasonography distinguishes psoriatic arthritis from rheumatoid arthritis – A cross-sectional study

Background: We aimed to evaluate the high-resolution ultrasonography (HRUS) findings in the hands of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA).Materials and Methods: This was a cross-sectional study of ultrasonography (USG) of hands in patients with PsA fulfilling the Classification criteria for psoriatic arthritis (CASPAR) in comparison with cases with RA fulfilling 1987 American College of Rheumatology classification criteria. Bilateral 1st and 2nd metacarpophalangeal (MCP) and proximal interphalangeal joints were assessed for synovitis and bone erosions, and extensor tendons at wrist for tenosynovitis by a single observer using the GE LOGIQ BOOK XP USG machine (General Electric Medical Systems) with a high-frequency 12-MHz linear array transducer. Demographic and clinical details were extracted from the electronic database of the hospital information system.Results: A total of 62 patients (31 with RA and PsA each) were studied. Demographic and baseline features were similar, except for more male patients in PsA as compared to RA (41.9% vs. 16.1%; P = 0.02). MCP synovitis was higher in RA as compared to PsA (71% vs. 29%; P = 0.001). Multiple logistic regression analysis found that absence of MCP synovitis by HRUS (adjusted odds ratio [OR]: 5.97; P = 0.02) in spite of higher number of swollen joints (adjusted OR: 29.3; P = 0.03) favors the diagnosis of PsA as compared to RA.Conclusion: “Our finding of fewer or no MCP synovitis by HRUS in PsA as compared to RA warrants a larger, powered validation study; if reproduced, it can be an additional tool to differentiate PsA including those without overt skin lesions from seronegative RA/early undifferentiated polyarthritis.”

Diagnostic accuracy of 14-3-3η protein in rheumatoid arthritis: A meta-analysis.

Dear Editor, We have read with great interest the article by Wang et al1 entitled “Diagnostic accuracy of 14-3-3η protein in rheumatoid arthritis: A meta-analysis”, which summarized available published studies on the diagnostic accuracy of 14-3-3η protein for rheumatoid arthritis (RA). A total of 13 studies (1554 positive and 1934 negative participants) were included in the study. The results demonstrated that the pooled sensitivity and specificity of 14-3-3η protein for RA were 0.73 (95% CI 0.71-0.75) and 0.88 (95% CI 0.87-0.90), indicating that 14-3-3η protein has moderate accuracy for the diagnosis of RA. Although we acknowledge the authors for their efforts to summarize the available data on this topic, we would like to raise several concerns needing further discussion. First of all, after searching related keywords in PubMed database, we found 2 articles fulfilled the inclusion and exclusion criteria of this meta-analysis but were not included by the authors. Carrier et al2 performed a 5-year prospective research involving 330 patients with early undifferentiated polyarthritis to evaluate the predictive capability of 14-3-3η protein for RA, revealing that 14-3-3η combined with other RA-associated biomarkers elevated the identification of RA patients. Zhang et al3 detected the serum level of 14-3-3η protein in 291 RA patients, 223 patients with autoimmune diseases except RA, and 156 healthy subjects to explore the application value of 14-3-3η protein for RA diagnosis, demonstrating that the sensitivity and specificity were 0.52 and 0.94 with a cut-off value of 0.2 ng/mL. Second, it seems that the authors made some mistakes in extracting the data of false positives (FP) and true negatives (TN). In the included study by Shovman et al4 the authors stated that the disease control group included 101 patients with different rheumatic diseases: 33 patients with systemic lupus erythematosus (SLE), 44 patients with ankylosing spondylitis (AS), and 24 patients with psoriatic arthritis (PsA), and the healthy control group comprised 66 healthy subjects. Moreover, the prevalence of 14-3-3η positivity in the control groups were 9% (SLE), 27% (AS), 12.5% (PsA) and 5% (healthy subjects), respectively. Thus the correct value of FP and TN should be 21 and 146, respectively. Finally, among the included studies, two publications by Maksymowych et al5, 6 shared overlapping groups of RA patients as the authors stated that “the 135 patients with established RA were previously described in Maksymowych, et al5” in the subsequent publication.6 Therefore, the data of the 135 RA patients were analyzed twice in the meta-analysis, thus increasing inappropriate weight to the duplicated data. We then performed a statistical analysis after adding the forementioned missed data, correcting the miscalculated value, and removing duplicated data with a total of 15 studies (2014 positive and 2339 negative participants) using the random-effects models. The pooled sensitivity and specificity were 0.66 (95% CI 0.64-0.68) and 0.89 (95% CI 0.87-0.90), respectively. The forest plots of pooled sensitivity and specificity are presented in Figure 1. The pooled positive and negative likelihood were 5.51 (95% CI 4.18-7.26) and 0.33 (95%CI 0.26-0.41), respectively. The pooled diagnostic odds ratio was 18.65 (95% CI 11.50-30.24), and the area under the curve of summary receiver operator characteristic was 0.9243 (Figure 2).

THU0179 PERSISTENCE IN RHEUMATOID ARTHRITIS PATIENTS ON BIOSIMILAR AND BIO-ORIGINATOR ETANERCEPT: A POOLED ANALYSIS OF PAN-CANADIAN COHORTS

Background:Biosimilar etanercept (ETA-B) was recently introduced in Canada but real-world data descriptions of drug persistence (and comparisons with the originator product, ETA-O) are still scarce.Objectives:To describe and compare persistence of ETA-B and ETA-O in RA.Methods:We used data from four ongoing, prospective cohorts in Canada: the Canadian Early Arthritis Cohort (CATCH), the Rheumatoid Arthritis Pharmacovigilance Program and Outcomes Research in Therapeutics (RAPPORT), the Early Undifferentiated Polyarthritis (EUPA) cohort, and the RHUMADATA® registry. We studied biologic-naïve and biologic-experienced RA adults initiating ETA-B or ETA-O between Jan. 2015 and Oct. 2019. Switchers from ETA-O to ETA-B (or vice-versa) were included. We assessed persistence of therapy in the first 12 or 24 months, measured as time from therapy initiation (time zero) to discontinuation. Individuals switching between products could contribute further person-time to the new exposure category. Multivariable Cox regression models were performed with each cohort dataset separately, following a common protocol. Model variables included age, sex, comorbidity, past biologic use, and disease duration. After testing for between-study heterogeneity (Higgin’s I2), cohort-estimated hazard ratios (HR) were pooled using random effects meta-analysis.Results:We identified 262 episodes of etanercept use (118 ETA-B and 144 ETA-O) from 250 RA patients. Sex, age, and other baseline characteristics across the four cohorts are shown in Table 1. Across cohorts, there was considerable variation in RA duration at the time of initiating ETA-B or ETA-O. In the pooled analysis, the HR for discontinuation at 24 months comparing ETA-B to ETA-O was 0.51 (95% confidence interval, CI: 0.26-0.98). The pooled analysis for therapy discontinuation at 12 months adjusted HR in this analysis was 0.82 (95% CI: 0.42-1.60).Table 1.Characteristics of studied patients according to their treatment episodes, biosimilar etanercept (ETA-B) or bio-originator etanercept (ETA-O).CharacteristicEUPARAPPORTRHUMADATACATCHETA-BETA-OETA-BETA-OETA-BETA-OETA-BETA-ON=19N=27N=32N=30N=39N=52N=28N=35Female sex, (%)12 (63)18 (67)20 (63)22 (73)28 (72)38 (73)20 (71)27 (77)Mean age in years1, SD59 (13)59 (16)51 (15)54 (15)59 (15)54 (15)55 (12)51 (13)Current smoker, (%)3 (17)5 (21)9 (32)5 (19)8 (21)9 (17)5 (18)8 (23)Cardiovascular disease, (%)0 (0)0 (0)1 (3.1)1 (3.3)8 (21)2 (4)NANADiabetes, (%)0 (0)0 (0)4 (13)1 (3)2 (5)3 (6)NANAHypertension, (%)NANA5 (16)4 (13)14 (36)22 (42)NANARA duration in years1, SD2 (3)7 (13)8 (6)12 (15)12 (12)9 (9)4 (4)3 (3)DAS-2812 (NA)4 (2.8)6 (1)6 (1)4 (2)4 (1)4.0 (2)4 (2)SDAI113 (14)44 (5)NANA21 (15)23 (8)23 (14)25 (16)Past oral steroids, N(%)Past biologic, N(%)15 (79)17 (63)6 (19)4 (13)29 (74)31 (60)9 (32)13 (37)Past non-biologic DMARD,8 (42)6 (22)2 (6)0 (0)21 (54)20 (38)19 (68)21 (60)N(%)19 (100)27 (100)30 (94)26 (87)39 (100)52(100)25 (89)33 (94)1At time zero or at the closest date before time zero. SD=standard deviationConclusion:Despite wide confidence intervals, the 24-month data suggested potential better persistence with ETA-B versus ETA-O, with a similar trend at 12 months. Some of the observed associations may be related to residual confounding (e.g. disease activity, time-dependent effects of concomitant medications) and/or survivorship bias (in patients transitioning from ETA-O to ETA-B).Disclosure of Interests:Cristiano S Moura: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Coupal: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Vivian Bykerk: None declared, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Sasha Bernatsky: None declared

Osteoclasts and their circulating precursors in rheumatoid arthritis: Relationships with disease activity and bone erosions

Patients with rheumatoid arthritis (RA) have very different outcomes, particularly with regard to bone erosions. Since osteoclasts are responsible for bone destruction adjacent to rheumatoid synovium, profiling osteoclasts from circulating precursors in RA could help identify patients at risk for bone destruction. In this study, we sought to determine whether the functional characteristics of osteoclasts generated from their blood precursors were modified by RA activity or were intrinsic to osteoclasts and associated with the RA phenotype (erosive or not).Osteoclasts were generated in vitro from peripheral blood mononuclear cells (PBMCs) of subjects with RA (n = 140), as well as sex- and age-matched healthy controls (n = 101). Osteoclastic parameters were analyzed at baseline and during the follow-up for up to 4 years, with regular assessment of RA activity, bone erosions, and bone mineral density (BMD). As a validation cohort, we examined RA patients from the Early Undifferentiated PolyArthritis (EUPA) study (n = 163).The proportion of CD14+ PBMC was higher in RA than in control subjects, but inversely correlated with the 28-joint disease activity score (DAS28). Also surprisingly, in osteoclast cultures from PBMCs, active RA was associated with lower osteoclastogenic capacity, while in vitro bone resorption per osteoclast and resistance to apoptosis were similar in both active and quiescent RA. In a small subgroup analysis, osteoclasts from subjects with recent RA that had progressed at four years to an erosive RA exhibited at baseline greater resistance to apoptosis than those from patients remaining non-erosive.Our findings establish that when RA is active, circulating monocytes have a reduced potential to generate osteoclasts from PBMCs in vitro. In addition, osteoclasts associated with erosive disease had resistance to apoptosis from the start of RA.

Arthritis risk with immune checkpoint inhibitor therapy for cancer.

This review summarizes the current evidence on inflammatory arthritis following cancer treatment with immune checkpoint inhibitors (ICI), and the effects of these therapies in patients with preexisting autoimmune arthritis. As the use of ICI for cancer therapy continues to expand, a myriad of immune-related adverse events (irAE) caused by these therapies are being recognized. Arthritis has been increasingly reported as a de novo irAE, presenting sometimes as a well defined disorder, such as rheumatoid arthritis or psoriatic arthritis, and in other occasions as undifferentiated monoarthritis, oligoarthritis, or polyarthritis. Remitting seronegative symmetric synovitis with pitting edema (RS3PE) and tenosynovitis have also been reported. Most published cases are reported as mild to moderate in severity. The most common treatment for arthritis has been systemic corticosteroids, although several patients have been treated with traditional disease-modifying antirheumatic drugs (DMARD), and a few, with biologic DMARD. Arthritis following ICI therapy is pleomorphic. Prompt identification and treatment are imperative to achieve optimal outcomes. Management should be multidisciplinary, including rheumatologists and oncologists, to ensure prompt symptomatic and functional management and continuation of cancer therapy as appropriate.

Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS)

BackgroundMethotrexate (MTX) remains the disease-modifying anti-rheumatic drug of first choice in rheumatoid arthritis (RA) but response varies. Predicting non-response to MTX could enable earlier access to alternative or additional medications and control of disease progression. We aimed to identify baseline predictors of non-response to MTX and combine these into a prediction algorithm.MethodsThis study included patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre prospective observational study of patients with RA or undifferentiated polyarthritis, commencing MTX for the first time. Non-response to MTX at 6 months was defined as “no response” using the European League Against Rheumatism (EULAR) response criteria, discontinuation of MTX due to inefficacy or starting biologic therapy. The association of baseline demographic, clinical and psychosocial predictors with non-response was assessed using logistic regression. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots.ResultsOf 1050 patients, 449 (43%) were classified as non-responders. Independent multivariable predictors of MTX non-response (OR (95% CI)) were rheumatoid factor (RF) negativity (0.62 (0.45, 0.86) for RF positivity versus negativity), higher Health Assessment Questionnaire score (1.64 (1.25, 2.15)), higher tender joint count (1.06 (1.02, 1.10)), lower Disease Activity score in 28 joints (0.29 (0.23, 0.39)) and higher Hospital Anxiety and Depression Scale anxiety score (1.07 (1.03, 1.12)). The optimism-corrected AUC was 0.74.ConclusionsThis is the first model for MTX non-response to be developed in a large contemporary study of patients commencing MTX in which demographic, clinical and psychosocial predictors were considered. Patient anxiety was a predictor of non-response and could be addressed at treatment commencement.

Associations rares ou trompeuses entre pathologies articulaires et pathologies hépato-gastro-entérologiques

In children, the combination of diarrhoea and arthritis can disclose rare disorders: tufting enteropathies, with excessive gut permeability; camptodactyly-arthropathy-coxa vara-pericarditis, sometimes associated with digestive features secondary to intestinal lymphangiectasia induced by the chronic constrictive pericarditis; IPEX syndromes (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) due to FOXP3 genetic defects, sometimes include a combinaison of arthritis and digestive troubles; the same holds true for APECED syndromes (mutations of AIRE). In adults, esophagus achalasia is associated with uveitis, and less frequently with psoriatic arthritis or Sjögren's syndromes. Ascitis can herald rheumatoid arthritis, and exsudative enteropathies worsen some Sjögren's syndromes. Mesenteric panniculitis have been observed in Sjögren's syndromes, rheumatoid arthritis and ankylosing spondylitis. The PPP syndrome (panniculitis-pancreatitis-polyarthritis) is consecutive to the systemic release of pancreatic enzymes. Its prognosis is poor if (false)-cysts from which enzymes are periodically discharged cannot be quickly surgically removed. In patients with undifferentiated polyarthritis, chronic cholostasis must lead to the search of anti-mitochondrial antibodies and anti-nuclear dots (indicative of primitive cholangitis). If such auto-antibodies are not found, a liver biopsy can reveal sclerosing cholangitis. Some arthritis can antedate auto-immune hepatitis (type 1, with anti-actin and/or anti-SLA antibodies, or type 2, with anti-LKM1 antibodies) which require a quick treatment by high doses of corticosteroids. Nodular regenerative liver hyperplasia can complicate lupus, polyarthritis, and Felty's syndromes.

Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 cases in Reunion Island from 2006-2012.

BackgroundSince 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients.Patients and methodsWe conducted a 6-year case series retrospective study in Reunion Island of patients referred to a rheumatologist due to continuous rheumatic or musculoskeletal pains that persisted following CHIK infection. These various disorders were documented in terms of their clinical and therapeutic courses. Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified according to validated criteria.ResultsWe reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy.ConclusionRheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials.

AB0448 Drug Survival of A Patients Cohort with Chronic Inflammatory RHEUMATISM Treated with Abatacept

ObjectivesThe persistence in therapy is an important assessment tool of therapy efficacy in patient with chronic disease. The aim of this study was to evaluate drug survival (DS) of a...

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels.

IntroductionWe hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity.MethodsSerum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables.ResultsIn both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort.ConclusionUsing both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production.

Étude et Suivi:Rheumatoid Arthritis in the 21st Century

For over 20 years much research in rheumatoid arthritis (RA) has focused on early identification and treatment of patients to prevent longterm joint damage, disability, and morbidity. A multitude of studies have demonstrated that early intervention improves outcomes, and in particular, treatment during the so-called “window of opportunity,” when patients first develop inflammatory arthritis, may halt development of chronic symptoms altogether1,2. We have new classification criteria3, developed specifically to aid early identification of patients who are likely to need disease-modifying therapy, and a host of new biologic drugs, in particular anti-tumor necrosis factor therapies, that have revolutionized our ability to suppress disease activity4. So how close are we to achieving the aims of longterm remission and minimal disability in clinical practice? In this issue of The Journal , Combe, et al report on the 5 year outcomes of the well established French ESPOIR cohort5. The developers of the ESPOIR “ Etude et Suivi des POlyarthritis Indifferences Recentes ” cohort, established to study and monitor early undifferentiated polyarthritis, should be congratulated on establishing a large nationwide cohort of patients with early undifferentiated inflammatory arthritis, providing real-world data on the progression of RA over time. By monitoring patients seen in clinic at regular intervals … Address correspondence to Dr. Verstappen; E-mail: suzanne.verstappen{at}manchester.ac.uk

AB0248 Application of targeted ultrasound initiative in management of rheumatoid arthritis in peruvian

BackgroundTUI (Targeted Ultrasound Initiative) and TURA (Targeted Ultrasound Rheumatoid Arthritis), have been proposed as additional tools for managing and improving outcomes in rheumatoid arthritis (RA) (1), with the main objectives:...

FRI0073 Diagnostic performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a cohort of early arthritis

BackgroundEarly diagnosis is a central issue in the management of rheumatoid arthritis (RA), and the insufficient sensitivity of the 1987 American College of Rheumatology (ACR) classification criteria in this setting...

THU0153 Does Ultrasonography Improve the Performance of the 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis?

BackgroundThe performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) using ultrasonography (US) as an alternative instrument to detect synovitis has recently been tested (1).ObjectivesTo evaluate the impact...

Characterization of Patients with Arthritis Referred for Gold Therapy in the Era of Biologics

To describe the clinical characteristics of patients referred for gold therapy and determine the reason for referral. We conducted a chart review of patients referred for gold at the Mary Pack Arthritis Program, Vancouver, Canada, from July 2007 to July 2009. The sample included 69 female and 12 male patients. Diagnosis was rheumatoid arthritis (RA) in 71/81, psoriatic arthritis in 5, juvenile idiopathic arthritis (JIA) in 2, Sjögren syndrome in 1, undifferentiated polyarthritis in 1, and spondyloarthritis in 1. Twenty of 81 patients had received gold before: 15 were referred for a second course, 4 a third course, and 1 a fourth course. Ten of 81 patients were referred for gold as their first disease-modifying antirheumatic drug (DMARD). Seventy-one had received prior DMARD: 1 prior DMARD in 22 patients, 2 in 24 patients, 3 in 15 patients, and > 3 in 6 patients. Four patients had received prior biologic therapy plus 2 to 4 prior DMARD. Twelve of 71 received gold monotherapy, 56/71 received gold/DMARD combinations, and 3 received gold/biologic/DMARD combinations. Reasons for referral included failure of other DMARD in 54 patients, limited DMARD options in 50 (chronic liver disease in 34, sulfa allergy in 7, high alcohol consumption in 5, and planning pregnancy in 4), physician choice in 12, previous benefit from gold in 10, benefit of clinic support in 10, inappropriate for biologics in 7, patient choice in 4, and failure of biologics in 3. The most common reasons for referral to gold clinic in 2007 to 2009 are failure of other DMARD and limited DMARD options due to underlying liver disease.

Long-term stability of anti-cyclic citrullinated peptide antibody status in patients with early inflammatory polyarthritis

IntroductionThe utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, particularly in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed therefore to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP).MethodsAnti-CCP and RF were measured at baseline and 5 years in 640 IP patients from the Norfolk Arthritis Register, a primary care-based inception cohort. The relation between change in anti-CCP status/titer and the presence of radiologic erosions, the extent of the Larsen score, and Health Assessment Questionnaire (HAQ) score by 5 years was investigated.ResultsWith a cut-off of 5 U/ml, 28% subjects tested positive for anti-CCP antibodies, 29% for RF, and 21% for both at baseline. Nine (2%) anti-CCP-negative patients seroconverted to positive, and nine (4.6%) anti-CCP-positive individuals became negative between baseline and 5 years. In contrast, RF status changed in 17% of subjects. However, change in RF status was strongly linked to baseline anti-CCP status and was not independently associated with outcome. Ever positivity for anti-CCP antibodies by 5 years did not improve prediction of radiographic damage compared with baseline status alone (accuracy, 75% versus 74%). A higher baseline anti-CCP titer (but not change in anti-CCP titer) predicted worse radiologic damage at 5 years (P < 0.0001), even at levels below the cut-off for anti-CCP positivity. Thus, a titer of 2 to 5 U/ml was strongly associated with erosions by 5 years (odds ratio, 3.6 (1.5 to 8.3); P = 0.003).ConclusionsRepeated testing of anti-CCP antibodies or RF in patients with IP does not improve prognostic value and should not be recommended in routine clinical practice.

Favorable effect of very early disease-modifying antirheumatic drug treatment on radiographic progression in early inflammatory arthritis: Data from the Étude et Suivi des Polyarthrites IndifféRenciées récentes (Study and Followup of Early Undifferentiate

While there is consensus that treatment with disease-modifying antirheumatic drugs (DMARDs) should be started early in patients with inflammatory arthritis, confirmation that radiographic progression is inhibited with early treatment start is scarce. This study was undertaken to compare radiographic progression in patients treated with a DMARD very early in the course of their disease (within 3 months of diagnosis) and those who began DMARD treatment later. Patients included in the French observational ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes [Study and Followup of Early Undifferentiated Polyarthritis]) cohort were followed up, and radiographic progression after 12 months was assessed. Propensity scores, reflecting the indication to start a DMARD, were obtained by modeling the start of DMARD therapy by disease-specific and demographic variables obtained at baseline, using logistic regression analysis. The influence of very early versus delayed DMARD start on radiographic progression was evaluated by generalized linear regression, with and without adjustment for propensity scores. Six hundred sixty-one patients were analyzed. In an unadjusted analysis, patients starting DMARD therapy within 3 months of diagnosis did not show a significant difference in radiographic progression score as compared to those starting DMARD therapy later (1.2 units versus 1.6 units; P = 0.37). Adjustment for the propensity score revealed a statistically significant difference in mean progression (0.8 units versus 1.7 units; P = 0.033). Analysis by propensity score quintile showed a trend suggesting that early treatment was especially beneficial for patients in the fourth and fifth quintiles (worse prognosis). Our findings indicate that among patients with inflammatory arthritis in daily clinical practice, early initiation of DMARD therapy reduces 12-month radiographic progression. This strengthens the current recommendations for very early initiation of specific therapy in patients with early arthritis.

Pain in arthritis

Under the term arthritis are grouped a large number of diseases characterized by the occurrence of an inflammatory process within the joints; between the different types of chronic arthritis, rheumatoid arthritis (RA) is the prototypical example. With the increasing importance of early diagnosis and treatment, in the last years several subsets of chronic arthritis have been described, starting from the early arthritis (EAs), term that include all the arthritis of recent onset; within the EAs we recognize the undifferentiated polyarthritis (UPA), that does not fulfill the classification criteria for an established chronic arthritis but that can turn into an established form of chronic arthritis overtime, and the early RA (ERAs), e.g., the arthritis of less than one year of duration fulfilling the ACR classification criteria for RA. Independently to the diagnosis, pain is a very common finding in this setting, deeply affecting patients’ quality of life and generally representing the first symptom of the disease and the reason of medical referral. Moreover, pain expression in chronic arthritis is not univocal, being influenced by several factors; in this paper we analyze the different aspects and the role of pain in chronic arthritis like (E)RA and UPA.