Early Arthritis Research Articles

Identification of a Human SOCS1 Polymorphism That Predicts Rheumatoid Arthritis Severity.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an autoimmune response in the joints and an exacerbation of cytokine responses. A minority of patients with RA experience spontaneous remission, but most will show moderate/high disease activity, with aggressive joint damage and multiple systemic manifestations. There is thus is a great need to identify prognostic biomarkers for disease risk to improve diagnosis and prognosis, and to inform on the most appropriate therapy. Here we focused on suppressor of cytokine signaling 1 (SOCS1), a physiological negative regulator of cytokines that modulates cell activation. Using four independent cohorts of patients with arthritis, we characterized the correlation between SOCS1 mRNA levels and clinical outcome. We found a significant inverse correlation between SOCS1 mRNA expression and disease activity throughout the follow-up of patients with RA. Lower baseline SOCS1 levels were associated with poorer disease control in response to methotrexate and other conventional synthetic disease-modifying anti-rheumatic drugs in early arthritis, and to rituximab in established (active) RA. Moreover, we identified several single nucleotide polymorphisms in the SOCS1 gene that correlated with SOCS1 mRNA expression, and that might identify those patients with early arthritis that fulfill RA classification criteria. One of them, rs4780355, is in linkage disequilibrium with a microsatellite (TTTTC)3−5, mapped 0.9 kb downstream of the SNP, and correlated with reduced SOCS1 expression in vitro. Overall, our data support the association between SOCS1 expression and disease progression, disease severity and response to treatment in RA. These observations underlie the relevance of SOCS1 mRNA levels for stratifying patients prognostically and guiding therapeutic decisions.

Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic damage and impact disability: a cross sectional study nested within a cohort

Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.

Limited Carpal Fusion in Kienböck's Disease: Early Results following Scaphocapitate Arthrodesis.

Background Kienböck's disease leading to progressive carpal collapse alters the wrist biomechanics leading to early arthritis and degenerative changes. Out of multiple surgical procedures present, no gold standard has been described. Scaphocapitate arthrodesis (SCA) is limited carpal fusion which shifts the loading axis toward radioscaphoid joint. This study presents the midterm clinical and radiological results of SCA in Kienböck's disease. Materials and Methods The data were reviewed from January 2016 to December 2017. Lichtman's classification used to stage the disease. Clinical variables were noted for wrist range of motion, grip strength, visual analog scale (VAS) score, quick disabilities of the arm, shoulder, and hand (quickDASH), and patient-rated wrist evaluation (PRWE) scores. Radiographs were evaluated for union, ulnar variance, carpal height ratio, radioscaphoid angle, and scapholunate angle. Results A total of 11 patients of Stage IIIA and IIIB Kienböck's disease with mean age of 24 years were included in the study with a minimum of 18 months of clinical follow-up. The procedure resulted in decreased ranges of motion but improved grip strength (26.09 ± 4.76 from 19.54 ± 4.63 kgf) and reduced pain with VAS score decreased from 7.36 ± 0.8 to 2 ± 1. Radiographic analysis showed union in all patients, reduced carpal height with a corrected radioscaphoid angle (from 62.12 to 48.3 degrees), and scapholunate angle (from 34 to 26.27 degrees). Discussion SCA has advantage of technical ease of orientation of the scaphoid and osteosynthesis of only one intercarpal joint with a large contact surface. Coupling the distal and proximal carpal rows results in significant loss of mean wrist range of motion but with improved grip strength, shifting the load away from the radiolunate joint. However, long-term studies are needed for clinical benefits and radiographic signs of radioscaphoid arthritis for the treatment of advanced-stage Kienböck's disease. Level of Evidence This is a Level IV, retrospective observational study.

Scaphoid Malunion Clinical and Radiographic Outcomes at a Minimum of 4 Years Follow-Up

To evaluate the radiographic and clinical outcomes of patients with scaphoid malunion after acute fracture at a mean of 7 years after injury. Patients with scaphoid malunion were identified from a departmental database of acute scaphoid fractures. Patients with a scaphoid height-to-length ratio greater than 0.6 on final follow-up computed tomography (CT) scan were considered malunited. These patients were contacted to return for CT imaging and clinical assessment. A total of 22 patients were included (4 females and 18 males). Average age of the group was 41 years (range, 16-64 years) and average length of follow-up was 7.4 years (range, 4.4-11.8 years) after injury. Ten patients who underwent CT imaging demonstrated arthritic changes at the radial styloid, scaphoid fossa, or scaphotrapeziotrapezoid joint(s). Despite this, patients had good clinical function that was not significantly different compared with the uninjured side. Patients reported minimal pain and disability based on patient-reported outcome measures, and there was a moderate correlation between passive range of motion and height-to-length ratio. Nearly half of all patients with malunited acute scaphoid fractures demonstrated radiographic findings of early arthritis on CT imaging but overall good clinical results on midterm follow-up. Prognostic IV.

SAT0559 INCREASED FREQUENCY OF INTER- AND SUBMETATARSAL BURSITIS AND MORTON’S NEUROMA IN RHEUMATOID ARTHRITIS: RESULTS OF A LARGE CASE-CONTROLLED MRI STUDY OF FOREFEET IN PATIENTS WITH EARLY ARTHRITIS AND HEALTHY CONTROLS

Background:The forefoot is a preferential location for tendon and joint inflammation in rheumatoid arthritis (RA). Some imaging studies suggested that intermetatarsal and submetatarsal pathology (such as bursitis and Morton’s neuroma) are also involved in RA, but these studies were small and its association was not thoroughly explored.Objectives:To determine whether intermetatarsal bursitis (IMB), Morton’s neuroma (MN) and submetatarsal bursitis (SMB) occur more often in early RA, compared to patients with other early arthritides and healthy controls. Contrast-enhancement in the subcutis that has been described as diffuse submetatarsal alterations (DSMA) were also included.Methods:In this cross-sectional cohort-study, consecutive patients with RA, other arthritides and healthy controls underwent MRI of unilateral forefoot. Two readers, a trained PhD-student an experienced MSK-radiologist, scored IMB, MN, SMB and DSMA in consensus, and measured transverse and dorsoplantar diameters of IMB, MN and SMB. Logistic regression models determined their association with RA, and test characteristics for RA were calculated. Lesion-sizes were plotted.Results:634 participants underwent MRI: 157 consecutive patients with RA (109 women; age 59±11SD), 284 with other early arthritides (158 women; age 56±17SD), and 193 healthy controls (136 women; age 50±16SD). Univariably, IMB, MN and SMB were more prevalent in RA (all P<0.001), DSMA was not (P=0.16). Multivariably, MB, SMB and MN were all associated with RA independent of each other (P<0.016). IMB was most frequent (sensitivity 69%), followed by SBM and MN (25% and 19%), specificity was high (70%, 96%, 94% respectively compared to other arthritides and 84%, 99% and 97% compared to healthy controls).Although IMB, MN and SNB were more frequent in RA, the lesion-size was mainly similar in all groups. For MN a dorsoplantar diameter >6mm or transverse diameter >5mm was highly specific (specificity 100% compared to healthy controls), however it was infrequent (sensitivity 12% and 13%, respectively). For IMB and SMB no cut-off size could be distinguished with high specificity.Conclusion:Intermetatarsal bursitis, Morton’s neuroma and submetatarsal bursitis are increased prevalent in early RA and could be considered as disease features.Disclosure of Interests:None declared

FRI0029 EFFECTIVENESS OF A NURSE LED TREAT TO TARGET (T2T) MODEL IN ACHIEVING REMISSION FOR EARLY RHEUMATOID ARTHRITIS PATIENTS IN A REAL-WORLD SETTING

Background:Rheumatoid Arthritis (RA) is a chronic, inflammatory and systemic autoimmune disease, affecting multiple joints particularly small joints in hands and feet.1For the past two decades, there has been significant change in approach for the diagnosis and treatment of RA. Now early diagnosis and aggressive management of RA is considered key role for preventing permanent damage to joints.2Treat to Target (T2T) strategy has been proven to be very effective in achieving pre-decided outcome either clinical remission (CR) or low disease activity(LDA).3Objectives:To assess the outcome of nurse led T2T strategy in Early RA patients within first 2 years of treatment.Methods:This was Observational Prospective Study, based on data collected in our ANP led Early Inflammatory Arthritis clinic. All patients diagnosed with inflammatory arthritis were managed following a T2T protocol. Every patient had predefined target set according to co-morbidities, preexisting osteoarthritis and duration of disease. Patients were followed up at varying intervals depending on clinical need until the steroid free target was achieved or for up to 2 years. Clinical Disease Activity Index (CDAI) tool was used to assess disease activity.Data collected included age, gender, diagnosis, Rheumatoid factor and/or Anti CCP positivity, erosions on x ray at the time of diagnosis and Health Assessment Questionnaire (HAQ-DI). For this analysis, only patients meeting the 2010 ACR/EULAR criteria4for the diagnosis of RA were included.The primary analysis in this study was the proportion of patients who achieved CR or LDA using different DMARDs used alone or in combination and the clinical determinants of this outcome.Results:Out of 417 patients with Early Inflammatory Arthritis, 300 met criteria for RA. 27 were lost to follow up (3 deaths) and 44 remained on the T2T pathway. For the 229 patients completing the pathway, mean age was 43.25 years (SD 9.405), Female gender 146 (63.75%), Anti CCP positive in 160 (69.86%), Rheumatoid Factor (RF) positive in 154 (67.24%), Both RF and Anti CCP positive 141 (61.57%), CDAI at baseline was 22.65 (SD 22.19) and Mean HAQ-DI at presentation 1.19 (SD 0.629). There were 18.34% (42) of patients who had erosive changes on x-ray at presentation.). Outcome of T2T strategy showed that 151 (65.93%) achieved clinical remission and 78(34.06%) achieved low disease activityConclusion:Remission in patients who were less than 40 years of age was 100% as opposed to 49% above the age of 40 years. This difference was found to be statistically significant with a p value of <0.05 (Table 1).Table 1.Treat to target outcomes with analysed variables.Group CharactersRemissionn (%)Low disease activity n (%)TotalP valueFemale92 (63.01)54 (36.99)1460.215Male59 (71.08)24 (28.92)83RF +103 (66.88)51 (33.12)1540.666RF -48 (64)27 (36)75CCP +105 (65.63)55 (34.37)1600.760CCP -44 (67.79)21 (32.31)65< 40 years76 (100)0 (0)760.000>40 years75 (49.02)78 (50.98)153Further to this, Methotrexate monotherapy was the dominant DMARD used to achieve remission and/or low disease activity in more than 50 % of the RA patients (Figure 1).

Novel biomarkers of a peripheral blood interferon signature associated with drug-na\xefve early arthritis patients distinguish persistent from self-limiting disease course

We profiled gene expression signatures to distinguish rheumatoid arthritis (RA) from non-inflammatory arthralgia (NIA), self-limiting arthritis (SLA), and undifferentiated arthritis (UA) as compared to healthy controls as novel potential biomarkers for therapeutic responsiveness. Global gene expression profiles of PBMCs from 43 drug-naïve patients presenting with joint symptoms were evaluated and differentially expressed genes identified by comparative analysis with 24 healthy volunteers. Patients were assessed at presentation with follow up at 6 and 12 months. Gene ontology and network pathway analysis were performed using DAVID Bioinformatics Resources v6.7. Gene expression profiles were also determined after disease-modifying anti-rheumatic drug (DMARD) treatment in the inflammatory arthritis groups (i.e. RA and UA) and confirmed by qRT-PCR. Receiver operating characteristic (ROC) curves analysis and Area Under the Curve (AUC) estimation were performed to assess the diagnostic value of candidate gene expression signatures. A type I interferon (IFN) gene signature distinguished DMARD-naïve patients who will subsequently develop persistent inflammatory arthritis (i.e. RA and UA) from those with NIA. In patients with RA, the IFN signature is characterised by up-regulation of SIGLEC1 (p = 0.00597) and MS4A4A (p = 0.00000904). We also identified, EPHB2 (p = 0.000542) and PDZK1IP1 (p = 0.0206) with RA-specific gene expression profiles and elevated expression of the ST6GALNAC1 (p = 0.0023) gene in UA. ROC and AUC risk score analysis suggested that MSA4A (AUC: 0.894, 0.644, 0.720), PDZK1IP1 (AUC: 0.785, 0.806, 0.977), and EPHB2 (AUC: 0.794, 0.723, 0.620) at 0, 6, and 12 months follow-up can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. In patients with early inflammatory arthritis, ST6GALNAC1 is a potential biomarker for UA as compared with healthy controls whereas EPHB2, MS4A4A, and particularly PDZK1IP1 may discriminate RA patients. SIGLEC1 may also be a useful marker of disease activity in UA.

OP0057 SEX SPECIFIC DIFFERENCES IN EARLY PSORIATIC ARTHRITIS

Background:Although the prevalence of Psoriatic Arthritis (PsA) is the same in men and women, women experience a higher burden of disease (pain, disability, fatigue) (1).The persistent belief that women tend to over-report their symptoms compared to men may also contribute to under or delayed diagnosis in women. The clinical pattern of PsA also differs, with men presenting more commonly with peripheral and axial joint damage and women being affected more frequently by polyarthritis (2). Furthermore, most disease activity measures contain pain and quality of life measurement metrics that may perform differently by sex. As a result, this may affect the clinician’s perception of disease severity, influence management decisions and subsequently introduce sex bias in prescribing.Objectives:To assess sex-related differences in baseline demographics, disease characteristics and evolution over 1 year in patients with newly diagnosed PsA.Methods:Our study is embedded in the Dutch south-west Early Psoriatic Arthritis prospective cohort study. We described patient characteristics using simple descriptive analysis techniques. For the comparison across sexes and baseline and 1 year follow up, appropriate tests depending on the distribution were used.Results:273 men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly fewer of them were in paid employment at baseline. Oligoarthritis was the most common pattern of arthritis in both sexes. Polyarthritis and enthesitis were more prevalent in women who also presented at baseline a significantly higher tender joint count (Fig.1) than men but no difference in swollen joint count.Figure 1.Longitudinal evolution of TJC68, Pain, VAS global, BRAF for men and women in the first year of PsA.All composite indices (CPDAI, DAPSA, GRACE, MDA, Psoriatic ArthritiS Disease Activity Score) showed significantly worse results in women at baseline. Women also suffered more frequently from comorbid medical conditions, fatigue and anxiety, and reported more severe limitations in function and worse quality of life.At 12 months women, despite the improvement they made, reported significantly higher levels of pain compared to men. Although MDA rates increase over time for both sexes,(Fig.2), it remained significantly more prevalent among men (19.0% vs 11.1% at inclusion,p<0.05, and 58.1% vs 35.7%,p<0.00, at T12). DAPSA was significantly higher in women at both timepoints and a significantly higher percentage of men presented remission according to DAPSA score at 12 months.Figure 2.Longitudinal evolution of composite measures for men and women in the first year of PsA.Conclusion:After 1 year of follow-up women didn’t surpass their baseline disadvantages and despite the improvement, they still present higher disease activity, more pain and lower functional capacity than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in psoriatic arthritis as sex-related difference in outcome persisted over time.

OP0040 ANTI-CITRULLINATED PROTEIN AUTOANTIBODIES ARE ASSOCIATED WITH ONGOING SYSTEMIC BONE LOSS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS TREATED ACCORDING TO THE PRINCIPLES OF TREAT-TO-TARGET AND TIGHT-CONTROL

Background:Anti-citrullinated protein antibodies (ACPA) are a major risk factor for local and systemic bone loss in patients with rheumatoid arthritis (RA). We previously demonstrated that early RA patients at disease presentation already show reduced systemic bone mineral density (BMD) in association with ACPA-positivity (1). Whether the negative impact of ACPA on bone continues over time despite treatment institution is however unknown.Objectives:To investigate longitudinally the course of systemic bone loss in patients with early RA after institution of treatment with disease modifying anti-rheumatic drugs (DMARDs) according to the principles of treat-to-target and tight-control.Methods:The study population included 100 consecutive early RA patients (<12 months of symptoms) recruited at our Early Arthritis inception cohort and already evaluated for systemic BMD at disease presentation before treatment start (1). After diagnosis, patients were prospectively followed-up at three-months intervals upon initiation of therapy with conventional synthetic DMARDs (methotrexate in 85% of the cases) aimed at the achievement of low disease activity (LDA, 28-joints disease activity score [DAS28] <3.2). BMD was re-assessed after 24 months at the lumbar spine (L1-L4) and hip by the same dual X-ray absorptiometry (DXA) equipment used at baseline. Differences in BMD from baseline were evaluated in relation to demographic and clinical variables (listed in Table 1).Table.Predictors of bone mineral density changes over 24 months% change in BMDlumbar spinetotal hipfemoral neckrprprpAge0.2690.0080.0690.500.2580.01female gender0.0850.42-0.0230.54-0.1210.23menopause0.1370.200.0670.530.0870.41disease duration0.0740.470.0440.670.0160.87cumulative DAS280.0180.860.0020.870.0110.91time to LDA0.1420.16-0.0230.76-0.0440.66time to remission0.0350.74-0.0020.97-0.0110.91ACPA-0.2510.010.1260.22-0.1300.04RF-0.1130.270.1110.280.0010.99months of bisphosphonates0.3680.0030.1710.090.2910.04cumulative steroids-0.1430.16-0.0070.78-0.0090.93months of bDMARDs-0.1630.11-0.0540.48-0.0630.54Results:The study population was mainly composed of females (84%), of whom 64.3% were in post-menopause; the mean (SD) age was 57.4 (13.5) years. Median (IQR) symptoms duration before treatment start was 14 (9-24) weeks. Fourty-three percent of the patients was ACPA positive. After 24 months of treatment, LDA was achieved in 79% of the cases, and remission in 46%; 17.7% of the patients had initiated a biological DMARD. At DXA re-scanning, the BMD at the lumbar spine and total hip remained largely unchanged, whilst at the femoral neck decreased from 0.726 g/cm2 to 0.713 g/cm2 (mean difference [SD] -0.013 [0.056], p=0.02). Predictors of BMD changes at different sites are shown in Table 1. The cumulative dose of prednisone was borderline significant for more BMD loss at the lumbar spine. Cumulative disease activity did not significantly affect BMD changes. Rather, ACPA-positive patients had higher percent changes at both the lumbar spine and the femoral neck. In multivariable analyses, ACPA remained associated with more BMD loss even when adjusting for confounders (age, gender, cumulative steroids, bisphosphonate treatment) (r -0.126, p=0.04 at the lumbar spine; r -0.126, p=0.04 at the femoral neck).Conclusion:Treatment of patients with early RA according to treat-to-target strategies prevents systemic bone loss. However, despite optimal disease control, ACPA positivity continues to be associated with progressive decline in systemic BMD.

THU0090 AGREEMENT BETWEEN REFERRING PHYSICIANS AND RHEUMATOLOGISTS AND PREDICTORS OF INFLAMMATORY ARTHRITIS: ANALYSIS BASED ON 8 YEARS OF EXPERIENCE IN AN EARLY ARTHRITIS CLINIC

Background:Early recognition of patients with arthritis is a crucial opportunity for optimal outcome. The Early Arthritis Clinic (EAC) of our department was created in 2012 to ensure a prompt access of these patients to efficient medical care. Patients may be referred based on a set of clinical criteria with less than 12 months duration and laboratory parameters: arthritis, inflammatory arthralgias, squeeze test, morning stiffness > 30 minutes, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR)>30mm/h and C-reactive-protein>0.5mg/dL (CRP).Objectives:To assess the level of agreement between the referring physician and the rheumatologist, regarding the presence of each of the six referral criteria and to identify predictors of inflammatory arthritis.Methods:Cross sectional study including patients aged ≥ 18-year-old observed in the EAC between January 2012 and October 2019. Subjects who were referred to the EAC by a rheumatologist and those without available referral letter/medical records from the first visit to the EAC were excluded. Demographic data, provenience, referral criteria (presence/absence) and the final diagnosis [presence or not of an inflammatory rheumatic disease (IRD)] were collected from medical records. For the six referral criteria, the agreement between the referring physician and the rheumatologist was assessed using the Cohen’s Kappa. The presence of each referral criteria was compared between patients with and without an IRD using χ2 tests. Variables with p<0.1 or clinically relevant were included in forward stepwise multivariable logistic regression analysis to identify possible predictors for IRD. The statistical analysis was performed using SPSS® v21 andp<0.05 was considered statistically significant.Results:376 patients (70% female; mean age (±SD) 56.3±16.2 years) were included. Most patients were referred from primary care (84%); the remaining 16% include those referred from emergency department and other hospital specialties. We diagnosed an inflammatory arthritis in 62% (n = 232) of the patients. Table 1 shows the level of agreement between the referring physician and the rheumatologist, regarding the presence of the referral criteria.Table 1.Agreement between the referring physician and the rheumatologist, regarding the presence of the referral criteria.Referral criteriaKappapArthritis0.230.05Squeeze test0.090.04Inflammatory arthralgias0.110.04Morning stiffness0.180.04RF0.270.04ESR0.260.04CRP0.250.04ANA0.020.47ANA- antinuclear antibodies; CRP- C-reactive-protein; ESR-erythrocyte sedimentation rate; RF-Rheumatoid factorIn univariable analysis (IRD Vs non-IRD), inflammatory arthralgias (74% Vs 93%, p=0.01), squeeze test (24% Vs 55%, p=0.01), morning stiffness (49% Vs 63%, p=0.05), ESR (63% Vs 46%, p=0.01), CRP (62% Vs 48%, p=0.04) were associated to IRD. In multivariable analysis, only ESR (OR 5.0 [95% CI 1.9-13.0], p < 0.05) and inflammatory arthralgias (OR 0.15 [95% CI 0.04-0.52], p < 0.05) remained as predictors of IRD.Conclusion:Agreement between the referring physicians and the rheumatologist regarding then presence/absence of the referral criteria was poor in all clinical criteria and fair in laboratory criteria. Elevated ESR was an independent predictor of IRD and the description of inflammatory arthralgias was negatively correlated with IRD. These findings suggest the need to clarify the referral criteria used and to improve education among the physicians referring patients to the EAC.Disclosure of Interests:Luisa Brites: None declared, LILIANA SARAIVA: None declared, Ana Rita Cunha: None declared, Helena Assunção: None declared, Tânia Santiago: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Catia Duarte: None declared

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

SAT0654-HPR AN OUTCOME EVALUATION FOR THE NURSE-LED EARLY ARTHRITIS CLINIC ON THE DIAGNOSIS AND MANAGEMENT OF RHEUMATOID ARTHRITIS AT CARITAS MEDICAL CENTRE IN HONG KONG

Background:Rheumatoid Arthritis (RA) is a chronic, autoimmune, inflammatory disease that may cause progressive joint damage and deformity, leading to functional disability and reduced quality of life. However, there is often a long waiting time for the first assessment in Rheumatology Clinic by doctor. Development of rheumatology nurse-led clinic allows early assessment by qualified rheumatology nurse for patients with suspected RA. It may potentially facilitate the decision and treatment plan in the first doctor clinic. A nurse-led Early Arthritis Clinic (EAC) for RA patients had been established in Caritas Medical Centre (CMC) since January 2018.Objectives:To determine the effectiveness of the EAC by early identification of new cases of RA and to facilitate decision in early initiation of disease-modifying anti-rheumatic drugs (DMARDs) during the first doctor clinic assessment.Methods:New cases were screened and recruited by Rheumatology nurse from January to December 2018 to nurse-led EAC. The recruited new cases were seen in EAC around 1 to 4 weeks before the first doctor clinic. Rheumatology nurse performed nursing assessment in EAC according to the 2010 ACR-EULAR Classification of RA. These cases will be reviewed by Rheumatologist during the first doctor clinic for confirmation of diagnosis and formulation of treatment plan. If urgent problems were identified during assessment in EAC, patients would be prioritized to have an earlier doctor clinic appointment or hospitalization may be arranged.Results:A total of 128 patients with articular symptoms were seen in nurse-led EAC during the study period. Nursing assessment revealed that 71 patients were required further evaluation for the diagnosis of RA (26 males and 45 females, mean age for males: 51, mean age for females: 56) and they were recruited into the study. 36 of these 71 patients were confirmed with the diagnosis RA by rheumatologist during the first consultation of doctor clinic. 13 of 36 patients were prescribed with DMARDs on the same day of consultation. Before the establishment of EAC, the mean time of confirmation of RA by rheumatologist was 8 weeks (range from 4 to 12 weeks). Therefore, EAC facilitates both the early diagnosis of RA and the prompt initiation of treatment after confirmation of diagnosis. Reduction in disease activity was also noted after treatment. The mean Disease Activity Score of 28 joints (DAS 28) during the assessment in EAC was 4.66 (range 3.22 to 6.54) while post treatment after EAC and the first doctor clinic was 3.30 (range 2.08 to 5.16) with mean difference of -1.36 (p<0.01). Other diagnoses were also made among the 71 patients. 8 patients were diagnosed of Spondyloarthropathy, 2 patients were diagnosed of psoriatic arthritis and 2 patients were diagnosed of systemic lupus erythematosus. 3 of these 71 patients were identified urgent medical problems required early intervention. Among these 3 cases, two patients with liver function derangement and one of them needed hospital admission for assessment of acute hepatitis. Another patient was arranged hospitalization to rule out sepsis due to raised total white cell count and erythrocyte sedimentation rate.Conclusion:Rheumatology nurse assessment in EAC is effective in assessing patients with suspected diagnosis of RA. It shortened the time to confirm the diagnosis of RA, and facilitated the decision on treatment plan. It effectively improved the disease activity of patients due to the prompt initiation of DMARDs by Rheumatologist.

Achievement of remission in two early rheumatoid arthritis cohorts implementing different treat-to-target strategies.

To compare achievement of remission in two early rheumatoid arthritis (RA) treat-to-target (TTT) cohorts, one tight control cohort targeting stringent remission in a randomized controlled strategy trial and one observational cohort targeting a looser definition of remission in clinical practice. We analyzed data from the ARCTIC trial and the NOR-VEAC observational study. Both were Norwegian multicenter studies including disease modifying anti-rheumatic drug (DMARD)-naïve RA-patients and implementing TTT. The target in ARCTIC was remission defined as a Disease Activity Score (DAS44) <1.6 plus 0 of 44 swollen joint count, while the target in NOR-VEAC was the less stringent remission of DAS28<2.6. We assessed achievement of the study-specific targets and compared achievement of the ACR/ EULAR Boolean remission during two years of follow-up. We included 189 patients from ARCTIC and 330 patients from NOR-VEAC. More than half in each cohort had reached the study-specific target at 6 months, increasing to more than 60% at 12 and 24 months. The odds of reaching ACR/EULAR Boolean remission during follow-up were higher in ARCTIC than in NOR-VEAC, with statistically significant differences at 3 months (OR 1.73; 95% CI 1.03-2.89), 12 months (OR 1.97; 95% CI 1.21-3.20) and 24 months (OR 1.82; 95% CI 1.05 - 3.16). A majority of patients in both cohorts reached the study-specific treatment targets. More patients in ARCTIC than in NOR-VEAC achieved ACR/EULAR Boolean remission during follow-up, suggesting that targeting a more stringent definition of remission provide further potential for favorable outcomes of a TTT strategy.

Treatment-resistant synovitis and radiographic progression are increased in elderly-onset rheumatoid arthritis patients: findings from a prospective observational longitudinal early arthritis cohort study

BackgroundClinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. MethodsPatients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. ResultsEORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells. ConclusionEarly EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes.

Lyme disease: diagnosis and treatment

Lyme disease is an important, vector-borne infection found throughout the temperate Northern hemisphere. The disease causes rash, acute systemic illness, and in some untreated patients, inflammatory arthritis. This review examines the emergence, clinical features and management of early Lyme disease and Lyme arthritis. There has been continuing progress in characterizing the clinical manifestations, diagnostic testing and treatment of Lyme disease. Almost all patients with early Lyme disease can be cured with antibiotic treatment. In most cases, Lyme arthritis also responds to antibiotics, but some patients require additional treatment approaches. The diagnosis of Lyme disease is based on clinical manifestations and adjunctive laboratory testing. For the rheumatologist, Lyme arthritis should be recognized by a pattern of attacks of asymmetric, oligo-arthritis, recognizable by clinical manifestations in the same way that other rheumatic diseases, such as gout or rheumatoid arthritis, are diagnosed.

Referring early arthritis patients within 6 weeks versus 12 weeks after symptom onset: an observational cohort study.

The first recommendation of the European League Against Rheumatism for the management of early arthritis states that patients should be referred to, and seen by, a rheumatologist within 6 weeks after symptom onset. However, implementation of this recommendation is a challenge, and evidence supporting this timeframe compared with longer timeframes is absent. Therefore, we aimed to investigate whether visiting a rheumatologist within 6 weeks of symptom onset relates to improved long-term outcomes compared with visiting a rheumatologist between 7 and 12 weeks after symptom onset. In this observation cohort study, consecutive patients with rheumatoid arthritis from the Leiden Early Arthritis Clinic (EAC) and the French Etude et Suivi des Polyarthrites Indifferenciées Recentes (ESPOIR) were included. In this analysis, we included patients who were diagnosed with rheumatoid arthritis and classified according to 1987 American College of Rheumatology criteria, and with symptom onset and remission data available. Patients were categorised into groups based on time between symptom onset and first encounter with a rheumatologist: within 6 weeks, between 7 weeks and 12 weeks, and after 12 weeks. The main outcomes were sustained disease-modifying antirheumatic drug (DMARD)-free remission and radiographic progression. Multivariable Cox regression, linear mixed models, and meta-analyses were used. 1025 patients with rheumatoid arthritis included in the EAC between Jan 1, 1996, and Dec 31, 2017, and 514 patients with rheumatoid arthritis included in ESPOIR between Nov 1, 2002, and April 30, 2005, were included in this analysis. Median follow-up was 7·1 years (IQR 3·9-12·2) in the EAC and 10·0 years (9·0-10·0) in ESPOIR. After 7 years of follow-up in the EAC, 30 (24%) of 127 patients with a time to encounter of 6 weeks or less, 45 (20%) of 223 patients with a time of 7-12 weeks, and 100 (15%) of 675 patients with a time of more than 12 weeks achieved sustained DMARD-free remission. After 10 years of follow-up in ESPOIR, three (27%) of 11 patients with a time to encounter of 6 weeks or less, 11 (11%) of 100 patients with a time of 7-12 weeks, and 41 (10%) of 403 patients with a time of more than 12 weeks had sustained DMARD-free remission. In the EAC multivariable analysis, patients who encountered a rheumatologist within 6 weeks obtained sustained DMARD-free remission more often than those seen between 7 and 12 weeks (hazard ratio [HR] 1·59 [95% CI 1·02-2·49], p=0·042), and after 12 weeks (1·54 [1·04-2·29], p=0·032). In the ESPOIR multivariable analysis, similar but non-significant effects were observed (HR 2·81 [95% CI 0·75-10·53], p=0·12, for within 6 weeks vs 7-12 weeks and 3·05 [0·89-10·49], p=0·077, for within 6 weeks vs more than 12 weeks). The meta-analysis of both cohorts showed that the time to encounter of 6 weeks or less was associated with a higher chance of achieving sustained DMARD-free remission than a time of 7-12 weeks (HR 1·69 [95% CI 1·10-2·57], p=0·016) and a time of more than 12 weeks (1·67 [1·08-2·58], p=0·020). The multivariable analysis showed that patients who encountered a rheumatologist within 6 weeks had similar radiographic progression to those seen between 7 and 12 weeks in both cohorts (β=1·00 [95% CI 0·95-1·05], p=0·96, in the EAC and 0·93 [0·80-1·07], p=0·30, in ESPOIR) and to those seen after 12 weeks (β=0·96 [95% CI 0·92-1·00], p=0·064, in the EAC and 0·89 [0·77-1·02], p=0·10, in ESPOIR). In the meta-analysis, a time to encounter of 6 weeks or less was not associated with less radiographic progression than a time of 7-12 weeks (β=0·99 [95% CI 0·95-1·04], p=0·75) but was associated with less radiographic progression than a time of more than 12 weeks (0·95 [0·91-0·99], p=0·028). Visiting a rheumatologist within 6 weeks of symptom onset had benefits for achieving sustained DMARD-free remission, but not for radiographic progression. European Research Council, Dutch Arthritis Society, Merck Sharp & Dohme, INSERM, The French Society of Rheumatology, Pfizer, AbbVie, Lilly, and Sanofi.

It's never too soon to treat rheumatoid arthritis: finally, some supportive evidence.

For the past 30 years, early arthritis clinics have been promoted as a means of improving long-term outcomes for patients, 1 the logic being that early therapy minimises structural damage (which correlates with longer-term functional loss) induced by inflammation both locally and systemically. 2 Furthermore, there is the long-held belief in the, at least theoretical, window of opportunity whereby early intervention permits a qualitatively better outcome than the same intervention applied at a later date. 1 A recent focus on individuals at risk of rheumatoid arthritis has led to the realisation that multiple pathological mechanisms are taking place before clinical signs of arthritis—eg, objective evidence of subclinical inflammation on sensitive imaging, 3 and immunological abnormalities in T-cell subset numbers.

Assessment of enthesitis in patients with psoriasis: Relationships with clinical features, screening questionnaries results, and quality of life: An ultrasound study

Background/Aim. Often asymptomatic, enthesitis can be an integral feature of the wide clinical spectrum in psoriasis as well as an early sign of development of psoriatic arthritis (PsA). It may be difficult to clinically recognize enthesitis in patients with psoriasis or distinguish it from other causes of extraarticular pain. Ultrasound (US) expanding use with the development of accurate assessments through standardized US algorithms as the Glasgow Ultrasound Enthesis Scoring System (GUESS) and the Madrid Sonographic Enthesitis Index Scoring System (MASEI) scores made the US the dominant imaging technique in diagnosing enthesitis. The aims of this study were to establish the prevalence of US signs of en-thesitis, compare it with screening questionnaires results, and estimate possible connections of US verified enthesitis with quality of life (QOL) of patients with psoriasis without PsA diagnosis. Methods. A cross-sectional study was performed on 67 patients with psoriasis who were without systemic therapy. The clinical presence of enthesitis was examined by an experienced rheumatologist, and systemic inflammation was estimated through serum level of C-reactive protein (CRP). The Psoriasis Area Severity Index (PASI) and Body Surface Area- Psoriasis (BSA-PsO) were calculated by a dermatologist. Visual analogue scale (VAS) for pain, screening questionnaires ? the Toronto Psoriatic Arthritis Screening (ToPAS), Psoriasis Ep-idemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE), Early Psoriatic Arthritis Screening Questionnaire (EARP), and Psoriasis and Arthrosis Screening Questionnaire (PASQ) ? were filled by patients. GUESS and MASEI scores were determined by US. The QOL was estimated by the Dermatology Life Quality Index (DLQI). Results. The presence of clinical enthesitis was recorded in 8.7% of patients. According to US signs of enthesitis using GUESS and MASEI scores, only 7% and 2% of patients, respectively, had no sign of enthesitis. Duration of psoriasis and age of subjects were in a significant correlation with GUESS and MASEI scores, while systemic inflammation, V AS v alue, PASI, and BSA-PsO scores were not. GUESS and MASEI scores significantly correlated with scores of all screening questionnaires as well as with DLQI. Conclusion. US can detect subclinical enthesitis better than clinical examination and widely used screening questionnaires, even though the correlations between MASEI and/or GUESS scores and results of screening questionnaires were positive. US examination is important in the multidisciplinary approach in diagnosing and managing psoriasis.

Septic arthritis of ankle joint in the paediatric age group: a retrospective study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Septic arthritis in paediatric age group poses a significant clinical problem. Common sites are hip and knee joint. There are several orthopaedic literatures available on septic arthritis of the hip and knee joint, however, literature on epidemiology, causative organisms and outcome of septic arthritis of the ankle are very few.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We conducted a retrospective study at a tertiary hospital with an aim to evaluate the incidence, causative pathogen, outcome and to identify differences, if any, between clinical features and laboratory findings of these patients when compared to those with hip and knee joint infection.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 47 children were diagnosed with septic arthritis, of which, 14 had septic arthritis of the ankle. Mean age was 5.2 years (8 months - 12 years). 13 children had undergone joint aspiration as a primary procedure. 50% (7) children had positive culture. &lt;em&gt;Streptococcus pyogenes&lt;/em&gt; was the commonest causative organism in our cohort (29%) followed by &lt;em&gt;Staphylococcus aureus&lt;/em&gt;. Mean follow-up was 36 months (16 - 56 months). 13 children (93%) had good clinical outcome. 1 child developed early arthritis.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Septic arthritis of the ankle is a serious condition. Even-though the joint is superficial, diagnosing it clinically can be difficult due to less pronounced symptoms. This can lead to delay in establishing the diagnosis and commencing treatment, hence, it is imperative to have a high index of suspicion. We found early joint aspiration followed by a course of antibiotics to be an effective regimen in management of this devastating condition.&lt;/p&gt;

Data quality predicts care quality: findings from a national clinical audit

BackgroundMissing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance.MethodsThe National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment.ResultsSix thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001).ConclusionsWe have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator.