Early Undifferentiated Arthritis Research Articles

A1.9 Pilot work towards discovery of novel diagnostic biomarker for rheumatoid arthritis using combinations of chemokine receptor expression on peripheral blood cell-subsets

Background and ObjectivesRheumatoid Arthritis (RA) is an autoimmune inflammatory joint disease resulting in joint damage and functional loss. Management is centred on early intervention, proven to prevent disabling joint damage...

Repeated Anticitrullinated Protein Antibody and Rheumatoid Factor Assessment Is Not Necessary in Early Arthritis: Results from the ESPOIR Cohort

Presence and levels of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) contribute to the classification and prognosis of rheumatoid arthritis (RA). The objective was to determine the usefulness of repeating anti-CCP/RF measurements during the first 2 years of followup in patients with early arthritis. In patients with early undifferentiated arthritis, serial anti-CCP and RF were measured using automated second-generation assays every 6 months for 2 years. Frequencies of seroconversions (from negative to positive or the reverse) and changes in antibody levels during followup were determined. In all, 775 patients, mean (SD) age 48.2 (12.5) years, mean symptom duration 3.4 (1.7) months, 76.6% female, were analyzed; 614 (79.2%) satisfied the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA at baseline. At baseline, respectively for anti-CCP and RF, 318 (41.0%) and 181 (23.4%) patients were positive, of whom 298 (93.7% of the positive) and 111 (61.3% of the positive) were highly positive (above 3 × upper limit of the norm). There were only 12 anti-CCP seroconversions toward the positive (i.e., 2.6% of the anti-CCP-negative), 21 seroconversions toward the negative (6.6% of the anti-CCP-positive), and 8 (1.0%) changes to a higher anti-CCP level category during the 2-year followup; respectively for RF, 27 (4.6%), 95 (52.5%), and 13 (1.7%). In this cohort of patients with early arthritis, including in the subset of patients who did not fulfill the RA criteria, antibody status showed little increase over a 2-year period. Repeated measurements of anti-CCP/RF very infrequently offer significant additional information.

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

The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

ObjectivesTraditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm2) have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies.MethodsSynovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11) were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC) analysis and naïve Bayes classifier were used to compare the abilities of (1) the absolute densities of cells expressing a given marker (absolute method) with (2) the percentages of these cells in the inflammatory cell population (relative method) to differentiate among the six tissue classes.ResultsThe inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm2.ConclusionsThis exploratory investigation featuring a variety of joint disorders revealed that measuring the relative proportions of inflammatory cell types may aid in synovial tissue classification if the samples are also stratified according to the intensity of inflammation.

SAT0415 Diagnostic and predictive value of novel method for analyzing IGG galactosylation in rheumatoid arthritis

BackgroundWhile the emphasis in rheumatoid arthritis (RA) treatment is on early diagnosis and intervention, we cannot provide the certain strategies for diagnosis. It is well known that serum immunoglobulin G...

FRI0061 Remission after one year follow up of the improved-study, a randomized clinical trial aiming at remission in patients with early rheumatoid and undifferentiated arthritis

ObjectivesTo evaluate the 1 year clinical outcomes of remission steered therapy in early arthritis, initially with methotrexate (MTX) and a tapered high dose of prednisone, in case of remission followed...

THU0416 The usefulness of a musculoskeletal ultrasound (MUS) scoring system for 22 hand joints examination for the detection of early undifferentiated inflammatory arthritis and treatment decisions making in established inflammatory arthritis

BackgroundThe ultrasound examination of the small joints in patients with inflammatory arthritis is extensively used in clinical routine at present despite the lack of a uniformly standardised scoring system.Objectives1) To...

AB0398 Dispositional optimism and depression severity in early arthritis patients treated with adalimumab and DMARD-combination therapy in the improved study

ObjectivesChronic inflammation is associated with depressive symptoms and low positive affect. We aimed to assess dispositional optimism and depression severity in patients with early arthritis after one year of remission...

FRI0502 After how many time does it become useless to try to classify an inflammatory rheumatism?

BackgroundThere is several models to predict the development ofrheumatoid arthritis in patients with early undifferentiated arthritis (UA). No study have concerned the future of the patients with UA in the...

SAT0008 Early RA Patients Fulfilling the New 2010 Acr/Eular Criteria, Display Better Clinical Responses to Dmard Therapy but have Higher Radiographic Damage Progression than Patients with Early RA not Fulfilling the 2010 Acr/Eular Criteria

BackgroundNew ACR/EULAR criteria for the classification of rheumatoid arthritis (RA) were recently proposed.ObjectivesThe aim of this analysis was to examine the impact of fulfilling the 2010 ACR/EULAR criteria at the...

FRI0155 Patient reported outcomes in early arthritis patients

BackgroundBesides suppression of inflammation and prevention of radiographic damage, improvement of functional ability and Health Related Quality Of Life (HRQOL) is one of the main goals of treatment in patients...

AB0329 The new 2010 ACR/eular classification criteria as possible predictor of treatment responses in early RA: Results from the swiss prospective observational RA cohort

BackgroundNew ACR/EULAR criteria for classification of rheumatoid Arthritis (RA) were recently proposed. The aim of this analysis was to examine the impact of fulfilling the 2010 ACR/EULAR criteria at the...

FRI0094 Outcomes of two years of remission steered treatment in early arthritis patients

ObjectivesTo evaluate the 2 year clinical outcomes of remission steered therapy in early arthritis patients in the IMPROVED study.Methods610 patients with early rheumatoid or undifferentiated arthritis (RA or UA) started...

SP0049 MRI in psoriatic arthritis - update on the current state

The clinical appearance of psoriatic arthritis (PsA) is very diverse, involving the spine, sacroiliac joints, peripheral joints and/or entheses, and accordingly MRI findings vary. PsA shares clinical manifestations with rheumatoid...

THU0154 Disease Characteristics and Predictors of Development of RA: A 2-Year Follow-Up Study of 658 Patients with Undifferentiated Arthritis of Less Than 16 Weeks Duration

BackgroundIdentifying patients with undifferentiated arthritis (UA) who are destined to develop rheumatoid arthritis (RA) is important to allow early institution of disease modifying therapy.ObjectivesTo describe and compare the baseline characteristics...

A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study

ObjectivesTo assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis.Methods610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with...

Validation of a Prediction Rule for the Diagnosis of Rheumatoid Arthritis in Patients with Recent Onset Undifferentiated Arthritis

Objectives. To validate van der Helm-van Mil score (vHvM) and new ACR/EULAR criteria for the diagnosis of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). Patients and Methods. Adult patients with UA (swelling ≥2 joints of less than 6 months duration, without diagnosis, and never treated with disease modifying drugs). Results. Ninety-one patients were included. Mean age: 55.6 years (SD: 17.4), 74% females. Median symptoms duration was 2 months (IR: 1–4 months). Mean van der Helm-van Mil score was 6.9 (SD: 2). After a mean followup of 6.2 months (SD: 6), 40.7% patients fulfilled ACR 1987 RA classification criteria, 28.6% fulfilled other diagnostic criteria, and 31% remained as UA. Receiver operator characteristic curve's (ROC's) area under the curve (AUC) for the vHvM score for diagnosis of RA was 0.83. A cutoff value of 6.94 showed sensitivity of 81% and 79.7% specificity. For the new ACR/EULAR criteria, the ROC AUC was 0.93, and a value equal to or greater than 6 showed 86.5% sensitivity and 87% specificity. Conclusion. van der Helm-van Mil prediction score and the new ACR/EULAR criteria proved to be valuable for the diagnosis of RA in patients with early UA.

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study

IntroductionThe aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment.MethodsIn this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models.ResultsDuring year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL.ConclusionsIn early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms.Trial registrationsISRCTN11916566 and EudraCT2006-006186-16

Factors associated with fatigue in early arthritis: Results from a multicenter national French cohort study

Fatigue frequently occurs in patients with early arthritis (EA). Determinants of its severity are unknown. We aimed to identify the factors associated with fatigue in EA and changes in fatigue after 1 year of followup. The Evaluation et Suivi de Polyarthrites Indifférenciées Récentes (Assessment and Followup of Early Undifferentiated Arthritis) cohort study is a multicenter, prospective, national cohort of patients with EA. At baseline and every 6 months up to 1 year, we recorded sociodemographic, clinical, and treatment characteristics, Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF) and Short Form 36 (SF-36) scores for health-related quality of life (HRQOL), and fatigue severity by a visual analog scale (f-VAS) and the SF-36 vitality score (fatigue_SF36). We included 813 patients (77% women, mean ± SD age 48 ± 13 years). At baseline, fatigue as assessed by the f-VAS or fatigue_SF36 was independently associated with young age, female sex, low education level, smoking, increased Disease Activity Score in 28 joints (DAS28), waking up at night, Sjögren's syndrome, and worse AIMS2-SF physical, affect, and symptom scores. At 1-year followup, a favorable change in fatigue scores was associated with increased baseline AIMS2-SF physical and affect scores (better quality of life), high baseline fatigue scores, and improved 1-year AIMS2-SF affect scores. Age, sex, and change in AIMS2-SF physical score, DAS28, and hemoglobin or C-reactive protein level were inconsistently associated with change in fatigue scores. The AIMS2-SF affect score explained most of the variance in baseline fatigue score and was an important factor in 1-year change in fatigue score. Fatigue in EA is multifactorial. Its level and its course are strongly associated with HRQOL, notably the affect dimension. These results should help professionals inform patients about fatigue, explore its causes, and develop tailored interventions.

Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort

ObjectivesTo compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and...