Anti-citrullinated Peptide Antibody Positivity Research Articles

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

The Protective Effect of HLA-DRB1 and HLA-DQB1 Alleles to ACPA-Positive and RF-Positive RA in Albanian Population

BACKGOUND: The prevalence of rheumatoid arthritis (RA) and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. AIM: We conducted a preliminary study of the distribution of HLA-DRB1 and HLA-DQB1 first field level alleles in a sample of 100 Albanian patients with RA. METHODS: In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with RA and considering their rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) serologic subgroups. We compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. RESULTS: No differences were found between the controls and the RA patient group, but three statistically significant differences were found: an increase in DRB1*04 among ACPA-positive, RF-positive and ACPA-positive/RF-positive patients, a significant decrease in DRB1*11 among ACPA-positive/RF-positive, and also a decrease in DRB1*13 among RF-positive patient subgroups. The frequencies of DRB1 allotypes in ACPA+ and RF+ patients compared to their counterpart ACPA− and RF−patient subgroups showed the predisposing effect of HLA-DRB1*04 for ACPA and RF seropositivity (p, respectively, 0.0008 and 0.0017) and the protective role of HLA-DRB1*11 for ACPA and RF positivity (p, respectively, 0.007 and 0.02). The same protective role from the RF positivity is also found with the HLA-DRB1*13 alleles (p = 0.007). As far as the DQB1 locus is concerned, a protective association has been found between the HLA-DQB1*06 alleles with both RF+ and RF+ ACPA+ positivity (p, respectively, 0.05 and 0.04) when comparing the control group with the respective RA patient subgroups. In ACPA+ and RF+ patients compared to the ACPA− and RF− patient subgroups, the only detected difference was between RF (+) and RF (−) patients (p =0.04). CONCLUSION: The relatively low frequencies of DRB1*04 and high (DRB1*11 and DRB1*13) in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. Our study demonstrates that DRB1*11, DRB1*13 and DQB1*06 may be negatively associated with RA. Conversely, DRB1*04 may confer susceptibility to RA in Albanian population.

Risk stratification using anti-citrullinated peptide antibodies (ACPA) in polyarticular subtypes of juvenile idiopathic arthritis in adulthood.

Polyarticular juvenile idiopathic arthritis (pJIA) is a subset of juvenile idiopathic arthritis (JIA), divided into two subtypes according to the presence of rheumatoid factor : pJIA without rheumatoid factor (pJIA RF-) and pJIA with positive rheumatoid factor (pJIA RF+), this latter is characterised with more structural damage. Anti-citrullinated peptide antibodies (ACPA) are often associated with RF. The respective performance of ACPA versus RF in structural outcome in pJIA, and in particular in adulthood pJIA remains unknown. Therefore, the aim of this study was to determine whether ACPA could be of value to assess structural damage in pJIA persisting in adulthood. Patients with pJIA and available data for ACPA, RF and X-ray were included retrospectively. Structural damage was assessed by two independent blinded investigators using Sharp Van Der Heijde scores. 56 pJIA adult patients were included : 62% (35/56) had pJIA RF+ and 38% (21/56) pJIA RF-. ACPA positivity in pJIA was significantly associated with presence of RF (96% vs 26%, p<0.001 ). RF positivity was significantly associated with higher Sharp van Der Heijde erosion and total scores (respectively p< 0.01 and p< 0.05 ). There were higher Sharp Van Der Heijde erosion, joint space narrowing and total scores in the pJIA ACPA+ subgroup than in the pJIA ACPA- subgroup, although there was no statistical significance. However, when adjusted on disease duration, pJIA ACPA+ patients had significantly higher erosion and total scores than pJIA ACPA- patients (p<0.05), and pJIA ACPA+ patients required more bDMARDs than pJIA ACPA- patients (p<0.05). Moreover, pJIA patients with high Sharp van Der Heijde joint space narrowing and total scores had significantly higher ACPA levels (p<0.01). A correlation was identified between ACPA levels and Sharp van Der Heijde total score ( r=0.54, p<0.05). In the pJIA RF+ subgroup the presence of ACPA was associated with additional structural damage compared to no ACPA: sharp Van Der Heijde erosion, joint space narrowing and total scores were higher in the pJIA RF+ ACPA+ subgroup than in the pJIA RF+ ACPA- subgroup although these results did not reach significance. Our results suggest that pJIA RF+ ACPA+ adult patients may have a more severe articular phenotype than pJIA RF+ ACPA- patients. ACPA could bring an additional value to RF for pJIA patients regarding structural damage. Altogether our results show that RF and ACPA are associated with structural damage measured by Sharp Van Der Heijde score in pJIA persisting in adulthood.

Risk factors for rheumatoid arthritis-associated interstitial lung disease: a retrospective study.

The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged ≥18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission.

Clinical Implications of Shared Epitope and Anti-citrullinated Peptide Antibody in Patients With Rheumatoid Arthritis.

The shared epitope (SE) and anti-citrullinated peptide antibody (ACPA) are involved in the pathogenesis of rheumatoid arthritis (RA). This study evaluated the clinical implications of SE and ACPA in terms of disease manifestation and response to biologic disease modifying anti-rheumatic drugs (DMARDs). Patients with identified human leukocyte antigen (HLA)-DRB1 alleles were included to compare the clinical characteristics and drug survival rate of tumor necrosis factor (TNF) inhibitors or abatacept based on the presence of SE and ACPA. Of the 533 patients with identified HLA-DRB1 alleles, 329 patients (61.7%) with SE alleles showed higher disease activity and erosive changes compared to patients without SE alleles. SE-positive patients were more likely to start biologic (b-) or targeted synthetic DMARDs (tsDMARDs) within the first 5 years (p=0.020). The presence of SE, smoking, dyslipidemia, and higher erythrocyte sedimentation rate were independently associated with the initiation of b- or tsDMARDs (p=0.016, 0.028, 0.031, and 0.001, respectively). The presence of SE and ACPA did not affect the drug survival rate of TNF inhibitors, whereas the abatacept retention rate was higher in ACPA-positive patients (p=0.024). The presence of SE affected disease characteristics and prognosis in Korean patients with RA without a significant impact on drug survival rate of TNF inhibitors and abatacept. ACPA positivity was associated with abatacept drug retention, suggesting that abatacept may be helpful in ACPA-positive patients than in ACPA-negative patients.

Seronegative rheumatic arthritis has milder inflammation and bone erosion in an ultrasound study of disease-modifying anti-rheumatic drugs (DMARDs)-naïve Chinese cohort.

BackgroundCompared with the seropositive rheumatic arthritis (sp-RA), seronegative rheumatic arthritis (sn-RA) lacks ultrasound (US) research. It is unknown whether sn-RA patients had more severe synovitis than sp-RA ones at the same level of swollen joint counts (SJCs). We designed the US study to find out the answers.MethodsAll cases satisfied the 2010 classification criteria, first diagnosed and disease-modifying anti-rheumatic drugs (DMARDs) naïve with the characteristics of abnormal swelling or pain in the wrist, proximal interphalangeal (PIPs), and metacarpophalangeal (MCPs) joints. Demographic data was collected. US examinations, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale scores (VASs), patient global assessment (PGA), physician’s global assessment (PhGA), disease activity score of 28 joints (DAS28), and van der Heijde-modified Sharp score (vdHSS) were used to evaluate the disease activity among these groups. Anticitrullinated peptide antibody (ACPA), rheumatoid factor (RF) and SJCs were used to divide the patients into 3 groups, which were defined as follows: Group A, sp-RA (positive RF and/or ACPA) with SJC >10; Group B, sp-RA with SJC ≤10; and Group C, sn-RA (all negative RF and ACPA with SJC >10 due to the criteria).ResultsA total of 139 cases were recruited. Fifty-six were Group A, 54 were Group B, and 29 were Group C. All indexes above and the total US scores were significantly lower in Group C than Group A (both groups with SJC >10) (ESR, CRP, VASs, PGA, PhGA, DAS28, vdHSS, US total score respectively: 58.8 vs. 37.5, P=0.009; 37.5 vs. 17.8, P=0.008; 61.7 vs. 52.8, P=0.032; 62.2 vs. 53.9, P=0.031; 59.8 vs. 48.3, P=0.029; 6.92 vs. 5.56, P=0.000; 61.7 vs. 44.5, P=0.023; 31.4 vs. 20.9, P=0.000). The difference of the total US scores above was mostly contributed by the symptoms of synovitis. The total US scores were prominently lower in Group C with the duration over 2 years (2–5 years, >5 years, respectively compared to <2 years: 16.3 vs. 27.4, P=0.044; 16.5 vs. 27.4, P=0.048), and vdHSS were remarkably higher in almost all groups with a duration of over 5 years. For the patients with a duration over 2 years, bone erosions occurred earlier in sp-RA than in sn-RA patients.ConclusionsSn-RA patients had milder synovitis than sp-RA ones at the same extent of disease activity. In addition, sn-RA had delayed progress of bone erosion than the sp-RA group.

Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.

Introduction Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.

Disease characteristics in high versus low titers of rheumatoid factor or anti-citrullinated peptide antibody in rheumatoid arthritis patients

Aim of the workTo evaluate the impact of the level of rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA) positivity on the clinical manifestations, disease activity, functional status, and treatment strategy among rheumatoid arthritis (RA) patients. Patients and methodsIn this study, 120 consecutive RA patients were grouped according to the level of RF or ACPA positivity. Group 1: patients with low positive RF or ACPA and Group 2: those with high titer. Disease activity score (DAS28) and functional status using modified health assessment questionnaire (MHAQ) were assessed ResultsThe patients mean age was 46.9 ± 10.9 years and female to male ratio was 7:1. 44 (36.7%) patients had low positive RF/ACPA titers, 59 (49.2%) had high titers and 17 (14.2%) had negative RF/ACPA and were excluded. Patients' global assessment of disease activity was significantly higher among patients with high RF/ACPA titer compared to those with low titer (p = 0.04) and MHAQ tended to be higher (p = 0.058). Subcutaneous nodules (p = 0.037) were more frequent among those with high RF/ACPA titer. The cumulative (p = 0.012) and the current (p = 0.006) steroid doses administered both turned out to be significantly higher in the high positive RF/ACPA patient group. ConclusionPatients with high titer RF and\\or ACPA have factors that may contribute to poor outcome as the presence of reduced functional status which indicated by the higher MHAQ score, the need for higher daily and cumulative steroid doses as an indirect indicator of increased disease activity and in turn poor outcome.

Anti-Citrullinated Peptide Antibody Expression and Its Association with Clinical Features and Outcomes in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and objectives: Anti-citrullinated peptide antibody (ACPA), a characteristic antibody detected in rheumatoid arthritis, could be linked to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) via the formation of neutrophil extracellular traps. We investigated the rate of ACPA positivity in patients with AAV and evaluated the association of ACPAs with their clinical features and outcomes. Materials and Methods: A total of 168 AAV patients with both ACPA and ANCA results at diagnosis were identified. Clinical and laboratory variables, including the disease-specific indices of Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS), were investigated. All-cause mortality, relapse, and end-stage renal disease, as well as interstitial lung disease (ILD) were evaluated as outcomes of the patients, and the Kaplan–Meier survival analysis was used to compare the event-free survival rates of the groups. Results: Fifteen (8.9%) and 135 (80.4%) patients were positive for ACPA and ANCA, respectively. There were no significant differences in the baseline variables of ACPA-negative and ACPA-positive patients. The absolute titre of ACPAs also did not significantly correlate with BVAS, FFS, erythrocyte sedimentation rate, or C-reactive protein. In addition, there was no difference noted regarding overall, relapse-free, and ESRD-free survival rates between ACPA-negative and ACPA-positive AAV patients. However, when the patients were divided into four groups according to ACPA and ANCA status, differences were present in the outcomes, and the ACPA-positive ANCA-positive group exhibited the lowest cumulative relapse-free survival rate, while no significant difference was present in the relapse between the ANCA-positive ANCA-positive, ACPA-positive ANCA-negative, and ACPA-negative ANCA-positive groups. Finally, the cumulative ILD-free survival rates were comparable between ACPA-positive and ACPA-negative AAV patients. Conclusions: The detection of ACPA expression is not uncommon in AAV. However, the presence of ACPA did not influence patients’ basal characteristics and outcomes, suggesting that further exploration of the role of this antibody is needed in patients with AAV.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity

Objectives Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. Methods Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). Results There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. Conclusion Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Repeat serological testing for anti-citrullinated peptide antibody after commencement of therapy is not helpful in patients with seronegative rheumatoid arthritis.

To Investigate the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) define 'seropositive' rheumatoid arthritis (RA). Both predict unfavourable disease course, development of extra-articular features and treatment outcomes. We investigated the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. DMARD-naïve patients with RA according to the 1987 American College of Rheumatology criteria and disease duration of <96 weeks were enrolled. RF and ACPA levels were recorded at baseline and sequentially during triple DMARD therapy. A total of 368 patients were followed for a median of 272 weeks. Of 154 patients seronegative for ACPA at recruitment, 10 (6.5%) seroconverted at some point. Nine of these were positive for RF at baseline and baseline RF titre was predictive of seroconversion. Four (2.6%) patients remained seropositive. No patients seroconverted from negative to positive for both RF and ACPA. Median time to seroconversion for ACPA was 29 months. Persistent seroconversion of ACPA from negative to positive after diagnosis in patients with RA is uncommon. ACPA and RF double negative patients are highly unlikely to ever develop ACPA positivity with a risk <1%. It is therefore unlikely to be helpful or cost effective to perform serial ACPA measurements in patients with seronegative RA after commencement of a treat-to-target strategy.

AB0176 RISK OF ANTI-CITRULLINATED PEPTIDE ANTIBODIES AND RHEUMATOID FACTOR IN MALE SMOKERS: DATA FROM KUWAIT REGISTRY FOR RHEUMATIC DISEASES (KRRD)

Background:Smoking has been proposed to be associated with the development of anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA) patients.Objectives:To study the relationship between smoking and ACPA as well as smoking and RF in patients with RA in Kuwait Registry for Rheumatic Diseases (KRRD).Methods:Data on RA patients were extracted from KRRD from four major hospitals from February 2013 through December 2019. As females rarely smoke in Kuwait with a smoking prevalence of 3% in female RA patients in KRRD, females were excluded from the study population to reach the minimum statistical percentage needed to perform chi square test and assess the association between smoking and other variables. Statistical tests were applied where appropriate. Logistic regression was conducted to adjust for possible confounders including age, disease duration, comorbidities, family history of a rheumatic disease, ANA, treatment agents and disease activity and quality of life assessment tools.Results:A total of 863 RA male patients were studied with a mean age of 53.9±12.5 years and a mean disease duration 7.3±5.5 years. 652 (75.6%) had positive RF and 624 (72.3%) had positive ACPA. 431 (50%) had at least one comorbidity. 640 (74.2%) were on conventional disease modifying agents (cDMARD’s) and 223 (25.8%) were on biologic therapy. 183 (21.2%) were smokers. After adjustment of other factors, logistic regression showed that smokers were significantly different than non-smokers in terms of a positive ACPA (β=-1.051,p&lt;0.001, odds=4.019) and a positive RF (β=-0.804,p=0.019, odds=2.517).Conclusion:Smokers have a higher risk of expressing a positive RF and a positive ACPA in a male population. Smoking should be considered as a possible risk factor for RA and efforts should be done to educate the population to cease smoking to possibly lower that risk.

Disease Activity and Anticitrullinated Peptide Antibody Positivity Predict the Worsening of Ventricular Function in Rheumatoid Arthritis.

ObjectiveThis prospective study was designed to analyze the incidence and the factors associated with impairment in left ventricular systolic function (LVSF) overtime in patients with rheumatoid arthritis (RA) without overt cardiac disease. In particular, we verified the hypothesis that a relationship between worsening of LVSF and markers of RA disease activity exists.MethodsOne hundred forty outpatients with RA without overt heart disease underwent clinical, laboratory, and echocardiographic evaluation at baseline and after 35 (interquartile range [IQR] 23‐47) months of follow‐up. A clinical Disease Activity Index (CDAI) score greater than 10 indicated the presence of moderate‐high RA disease activity; data on anticitrullinated peptide antibody (ACPA) positivity were recorded at baseline. Stress‐corrected midwall fractional shortening (sc‐MFS) was used as a measure of LVSF and was considered impaired if less than 86.5%.ResultsAt 36 (IQR 23‐47) months follow‐up, impaired sc‐MFS was detected in 60 of 140 (43%) patients, compared with 80 patients with normal sc‐MFS. Disease duration and activity, ACPA positivity, inflammatory markers, cardiovascular and antirheumatic therapies, and sc‐MFS were similar between the two groups at baseline. A multiple logistic regression analysis showed ACPA positivity, moderate‐high disease activity (CDAI greater than 10), and disease duration as independent predictors of impaired sc‐MFS at follow‐up. Finally, a simple clinical score to predict worsening of LVSF at midterm was built (area under the curve of 0.80, with a sensibility and specificity of 78% and 82%, respectively).ConclusionDisease duration, ACPA positivity, and moderate‐high disease activity are independent prognosticators of LVSF impairment in RA. Adverse changes in heart function could be prevented by good control of inflammation and modulation of autoimmunity.

O37 Utility of RA classification criteria in early inflammatory arthritis referral prioritisation

Abstract Background Early arthritis clinics are increasingly utilised as a method of ensuring patients suspected of disease are assessed promptly to enable suitable treatment. Early recognition with treat to target has been demonstrated in systematic reviews to significantly improve mortality and morbidity outcomes. The United Kingdom’s National Institute for Health and Care Excellence (NICE) recommend potentially affected patients are referred from primary care within 3 days and seen in secondary care within 3 weeks. We hypothesised that utilising the ACR/EULAR 2010 rheumatoid arthritis classification criteria we could identify variables within the primary care referral which make an early arthritis more or less likely. Methods A retrospective study of all the patients seen in early inflammatory arthritis (EIA) Clinic from September 2017 to August 2018 in Aneurin Bevan University Health Board. EULAR scores of 145 patients were calculated based on the data provided in the primary care referral. These scores and their components were then compared to the eventual diagnosis. Results EULAR score of ≥ 5 had specificity of &amp;gt; 78% and sensitivity of &amp;lt; 30% in predicting EIA. EULAR score of 8 or more was 100% specific for EIA with positive likelihood ratio of infinity. Whereas EULAR score &amp;lt; 3 had a specificity of &amp;gt; 70% and sensitivity of &amp;lt; 45% for Non EIA with a positive likelihood ratio of 1.59. Considering individual EULAR components a high positive Rheumatoid Factor (RF) or Anti-citrullinated peptide antibody (ACPA) and involvement of greater than 10 joints had a positive likelihood ratio of ≥ 3.00 for EIA. A low positive RF or ACPA had a specificity of 66.67% and sensitivity of 27.59% for EIA with a positive likelihood ratio of 0.83. Surprisingly involvement of 4-10 small joints or 2-10 large joints or just 1 large joint had a specificity of ≥ 75% for EIA and a positive likelihood ratio of greater than 1.00. A positive ESR or CRP had a specificity of 36.84% and sensitivity of 67.92% with a positive likelihood ratio for EIA of 1.08. A negative ESR and CRP had a specificity of 67.92% and a sensitivity of 35.00% for Non EIA with a positive likelihood ratio of 1.09. The duration of symptoms of &amp;lt; 6 weeks had a specificity of 77.55% and sensitivity of 24.39% with positive likelihood ratio for Non EIA of 1.08, however duration of &amp;gt; 6 weeks had a positive likelihood ratio of 0.97 for EIA with a lower specificity of 22.45% . Conclusion The total EULAR score and individual components can be used to prioritize primary care referrals. A EULAR score of less than 3, duration of symptoms of &amp;lt; 6 weeks, a negative ESR and CRP, a low positive RF or ACPA makes EIA less likely. Disclosures S.M. Imaduddin None. P. O'Biern None.

Anti-citrullinated peptide antibodies with interstitial lung disease in patients with rheumatoid arthritis

Background Rheumatoid arthritis (RA)-associated diffuse interstitial lung disease (ILD) is a common extra-articular manifestation that causes significant morbidity and mortality. Anti-citrullinated peptide antibodies (ACPA) are a valuable marker in assessing worsening of articular injury in patients with RA. We studied the correlation of ACPA in patients with RA with ILD. Patients and methods A randomized controlled trial involving 45 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria was conducted. Patients were grouped into two groups: group I: RA with ILD (15 cases) and group II: RA without ILD (30 cases). Data, such as disease activity score (DAS), disease duration, ACPA by enzyme-linked immunosorbent assay technique, pulmonary functions, and radiographic evidence of ILD by chest high-resolution computed tomography, with estimation of ground-glass and reticular pattern scores, were collected. Results A total of 34 (75.6%) cases were ACPA positive, whereas 11 (24.4%) cases were anti-cyclic citrullinated peptide negative. Diffusion capacity for carbon monoxide reduced significantly in RA with ILD group (P=0.002). Reticular and DAS were significantly high in the ACPA-positive group (P=0.005). Moreover, there were statistically significant increases in erythrocyte sedimentation rate, C-reactive protein, and platelets but statistically significant decrease in white blood cells in in the ACPA-positive group. ACPA positively correlated with DAS (r=0.610) and erythrocyte sedimentation rate (r=0.472). RA disease duration positively correlated with the presence of ILD (P=0.000) and showed a strong negative correlation with diffusion capacity for carbon monoxide (P=0.04). The positive predictive value of positive ACPA was 78.8 for ILD, of which, 70% for ground glass, 100% for the reticular pattern. Conclusion ACPA is positively correlated with the presence of ILD in patients with RA.

Factors predicting early discontinuation of methotrexate as a first-line treatment for rheumatoid arthritis in Italy: Results from the GISEA registry

Objective: Despite the well-established efficacy of methotrexate (MTX) in rheumatoid arthritis (RA), monotherapy is not sufficient in almost half of patients. The aim of this registry-based study was to detect possible predictive factors for the early failure of MTX as a first-line treatment in early RA patients. Materials and Methods: Five-hundred and ninety RA patients beginning MTX as the first-line treatment were included. Persistence on therapy was re-evaluated after 12 months. Baseline features of disease were evaluated by means of univariate Cox regression, and parameters significantly associated to the outcome were included in multivariate model. Results: One hundred and forty-nine patients (25.3%) failed MTX during the 1st year, for inefficacy in 43.6% and adverse events in 37.5% of cases, respectively. At univariate analysis, patients who discontinued or failed treatment showed lower mean age, higher prevalence of anti-citrullinated peptide antibodies (ACPAs), and higher number of tender/swollen joints. The dose of MTX was correlated with the efficacy and the tolerance of the drug. In particular, patients treated with 7.5 mg of MTX weekly showed a higher rate of discontinuation for inefficacy than adverse events, and the contrary was detected for higher doses. On multivariate analysis, age, ACPA, and number of tender joints were directly associated with MTX discontinuation or failure. Conclusions: More than 25% of RA patients treated with MTX as a first-line therapy failed treatment at 12 months. ACPA positivity, age, and number of tender joints were associated with early withdrawal of MTX in RA patients, while the dose of MTX was correlated to the efficacy and safety of the drug.

Patients With Arthralgia and Anti-Citrullinated Peptide Antibody Positivity on Hydroxychloroquine Therapy: An Update on 2 and 3 Years' Follow-up Data of a Pilot Study.

Patients With Arthralgia and Anti-Citrullinated Peptide Antibody Positivity on Hydroxychloroquine Therapy: An Update on 2 and 3 Years' Follow-up Data of a Pilot Study.

Effect of cumulative exposure to corticosteroid and DMARD on radiographic progression in rheumatoid arthritis: results from the ESPOIR cohort.

Several authors have tried to predict the risk of radiographic progression in RA according to baseline characteristics, considering exposure to treatment only as a binary variable (Treated: Yes/No). This study aims to model the risk of 5-year radiographic progression taking into account both baseline characteristics and the cumulative time-varying exposure to corticosteroids or DMARDs. The study population consisted of 403 patients of the Etude et Suivi des Polyarthrites Indifférenciées Récentes cohort meeting the 1987 ACR or 2010 ACR/EULAR criteria for RA at inclusion and having complete radiographic data at baseline and 5 years. Radiographic progression was defined at 5 years as a significant increase of the Sharp/van der Heidje score (smallest detectable difference ⩾5). The best logistic regression model was selected from the following: model including only clinico-biological baseline characteristics; model considering baseline characteristics and treatments as binary variables; and model considering baseline characteristics and treatments as weighted cumulative exposure variables. Radiographic progression occurred in 143 (35.5%) patients. The best model combined anti-citrullinated peptide antibody positivity, ESR, swollen joint count >14 and erosion score at baseline, as well as corticosteroids, MTX/LEF (MTX or LEF) and biologic DMARDs (bDMARDs) as weighted cumulative exposure variables. Recent cumulative exposure to high doses of corticosteroids (⩽ 3months) was significantly associated with the risk of 5-year radiographic progression and a significant protective association was highlighted for a 36-month exposure to bDMARDs. Corticosteroids and bDMARDs play an important role in radiographic progression. Accounting for treatment class and intensity of exposure is a major concern in predictive models of radiographic progression in RA patients.

Interleukin-6 and IgA-rheumatoid factor are crucial for baseline erosiveness, and anti-citrullinated peptide antibodies for radiographic progression in early rheumatoid arthritis treated according to a treat-to-target strategy

Objectives: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients.Method: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy. At baseline and after 12 months, hand and foot radiographs were evaluated using the Sharp/van der Heijde erosion score.Results: At diagnosis, seronegative patients were older and had higher Disease Activity Scores (DASs) than seropositive patients. A higher risk of erosiveness at baseline was conferred by IgA-RF positivity and IL-6 plasma levels ≥7.6 pg/mL, particularly when simultaneously present. In multivariate analysis, disease duration and IL-6 plasma levels ≥7.6 pg/mL arose as independent variables associated with presence of erosions at onset. Radiographic progression at 1 year follow-up, which occurred in 11.1% of ERA patients, was predicted by ACPA positivity, together with higher age at diagnosis. Despite similar percentages of good European League Against Rheumatism response, DAS and Boolean remission being observed over time among seropositive and seronegative patients and between erosive and non-erosive subjects, ERA patients who were erosive at onset, IgA-RF seropositive, and simultaneously having high baseline IL-6 plasma levels (≥7.6 pg/mL) were treated to a greater extent with tumour necrosis factor blockers after 12 months.Conclusion: IgA-RF positivity and IL-6 plasma levels are crucial for baseline erosiveness, while ACPA positivity represents the strongest risk factor for developing radiographic progression in ERA.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography

Objective: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls.Method: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm.Results: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups.Conclusion: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.