Rheumatoid Factor Seropositivity Research Articles

Unmet Needs and Current Challenges of Rheumatoid Arthritis: Difficult-to-Treat Rheumatoid Arthritis and Late-Onset Rheumatoid Arthritis.

Despite remarkable advances in the management of RA, there are still unmet needs that rheumatologists need to address. In this review, we focused on difficult-to-treat RA (D2T RA) and late-onset RA (LORA), and summarized their characteristics and management. The prevalence of D2T RA is reported to be 6-28% and many factors have been identified as risk factors for D2T RA, including female sex, long disease duration, seropositivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody and their high titer, baseline high disease activity, and comorbidities. D2T RA is broadly divided into inflammatory and non-inflammatory conditions, and clinical features differ according to background. A proportion of D2T RA can be managed with treatment modification, mainly with interleukin-6 receptor inhibitors or Janus kinase inhibitors, but some D2T RA patients have a poor prognosis; thus, the implementation of precision medicine by stratifying patients according to disease status is needed. In the aging society, the epidemiology of RA is changing and the prevalence of LORA is increasing worldwide. LORA has distinct clinical features compared with young-onset RA, such as acute onset, low seropositivity, and high inflammation. The pathogenesis of LORA remains to be elucidated, but proinflammatory cytokines, including interleukin-6, have been reported to be significantly elevated. LORA has several management concerns other than RA itself, such as geriatric syndrome and multimorbidity. The treat-to-target strategy is effective for LORA, but the evidence is still lacking; thus, it is important to accumulate clinical and related basic data to establish the optimal treatment strategy for LORA.

Changes in Serum Rheumatoid Factor Following Eradication of Hepatitis C Virus Infection With Interferon or Direct Antiviral Therapy.

Hepatitis C virus (HCV) infection is associated with a myriad of extrahepatic manifestations (EHM), as well as the production of autoantibodies, including rheumatoid factor (RF). This study aims to elucidate whether serum levels of RF change before and after HCV eradication, and whether these changes differ according to the type of therapy used. This is a retrospective cohort study of adults with chronic HCV infection treated with interferon-free or interferon-based regimens. All patients had HCV viremia at baseline and documented sustained virological response (SVR) 12 or 24 weeks after completing treatment. We measured the serum levels of RF at baseline and at SVR-12 or -24 to analyse the changes after eradication. This study enrolled 297 patients (median age, 59 years; female, 48.5%; cirrhosis, 16.8%). Among them, 78 (26.3%) were RF-positive by qualitative serology at baseline. This number decreased to 49 (16.5%) at SVR-12 or -24 (p < 0.001). Quantitatively, the median RF also decreased from 1.6 IU/mL (interquartile range [IQR], undetectable-15.8) to undetectable (IQR, undetectable-6.6 IU/mL) (p < 0.001). Significant reductions were observed in both groups. The proportion with RF seropositivity decreased from 24.3% to 15.4% (p = 0.001) in patients treated with interferon-free agents (n = 214) and from 31.3% to 19.3% (p = 0.006) in patients treated with interferon-based regimens (n = 83), without significant difference between two groups (p = 0.40). Serum RF decreased after HCV eradication, regardless of treatment regimen. Our findings suggest that HCV eradication may attenuate HCV-related autoimmunity.

Real-world clinical outcomes and rationale for initiating abatacept as a first-line biologic for patients with anticitrullinated protein antibody- and rheumatoid factor-positive rheumatoid arthritis.

Aim: In rheumatoid arthritis (RA), seropositivity for both anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) is associated with disease severity and therapeutic response. Biologic (b) disease-modifying antirheumatic drugs (DMARDs) such as abatacept are recommended after inadequate response or contraindication to conventional synthetic DMARDs. This retrospective cohort study aimed to describe changes in Clinical Disease Activity Index (CDAI) measures over 12months among patients with ACPA+ and RF+ RA with an inadequate response to methotrexate treated with abatacept as a first-line bDMARD. Patients & methods: Patient data were abstracted from medical records by treating rheumatologists. Analyses included McNemar tests for paired proportions or paired t-tests to assess longitudinal changes in CDAI scores, and Kaplan-Meier methods for time-to-event outcomes. Serious AEs and rationale for initiating treatment were recorded. Results: Overall, 296 patients were included. Mean CDAI scores improved (decreased) by 34.0, 61.0 and 74.0% (all p<0.001) from baseline to 3-6months, 6-12months and ≥12months after abatacept initiation, respectively. Of 279 patients not in CDAI low disease activity (LDA) or remission at baseline, 24.7% of patients achieved it within 6months, 56.3% within 12months and 71.0% at any point during follow-up after abatacept initiation. Median time to CDAI LDA/remission was 10.2months. Serious AEs were reported in 2.4% of patients. Common reasons reported by rheumatologists for initiating abatacept were effectiveness/efficacy (52.7%), safety (31.4%) and patient preference (25.3%). Conclusion: In this analysis of patients with ACPA+ and RF+ RA treated with abatacept as a first-line bDMARD in a clinical practice setting, clinical outcomes and remission rates were improved at all time points, providing real-world evidence to further support the use of abatacept in this patient population.

Clinical and laboratory pattern of patients with systemic lupus erythematosus seropositive for rheumatoid factor.

The aim of the study was to investigate the associations between the presence and level of rheumatoid factor (RF) in the blood serum and the clinical and laboratory characteristics of patients with systemic lupus erythematosus (SLE). This retrospective tricentric cross-sectional study analyzed a Ukrainian contingent of SLE patients. Medical records of 495 patients were evaluated. Rheumatoid factor serum concentration was tested in 206 of them (41.6%) using turbidimetry technique. Clinical manifestations, routine laboratory parameters, specific immunological tests, disease activity (SLEDAI-2K), and damage indices (SLICC/ACR DI) were evaluated. Our study revealed that RF was elevated in 27.7% of patients. The RF-positive patients experienced a longer delay in SLE diagnosis (2.0 vs. 0.5 years, p = 0.046), less frequent kidney involvement (42.1% vs. 59.4%, p = 0.045) and fever (42.1% vs. 59.2%, p = 0.046), and more frequent lymphadenopathy (59.6% vs. 42.3%, p = 0.039) compared to RF-negative patients. Patients with RF positivity had higher levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA) titer, and were more frequently positive for antibodies to Ro/SSA and La/SSB. Rheumatoid factor concentration directly correlated with CRP (r = 0.318; p < 0.01) and ESR (r = 0.228; p = 0.04) levels. However, no associations were found between RF levels and SLEDAI-2K, joint involvement frequency, SLICC/ACR DI or drug therapy content. Univariate logistic regression analysis showed that RF positivity was independently associated with lymphadenopathy, presence of anti-Ro/SSA and anti-La/SSB antibodies, and negatively associated with kidney involvement. In RF-seropositive SLE patients (approximately 28%), the diagnosis is established later compared to RF-seronegative ones; kidney involvement and fever are less common, while lymphadenopathy develops more frequently. Rheumatoid factor seropositivity is associated with higher levels of ESR, CRP, ANA, and the presence of antibodies to Ro/SSA and La/SSB. According to the results of univariate logistic regression analysis, an independent association with RF positivity was confirmed only for kidney involvement, lymphadenopathy, and antibodies to Ro/SSA and La/SSB.

Pro-inflammatory cytokine IL-21 correlates with the reactive oxygen species and 25-hydroxy vitamin D in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder and its characteristics include the immune system's invasion of the healthy lining of the joints and the articular structures degeneration. The IL-21 pro-inflammatory cytokine, and the reactive oxygen species (ROS) might have a role in the RA etiopathogenesis. The present study assessed the correlation of IL-21 with vitamin 25(OH)D and the ROS. The study included 120 RA patients and 60 healthy group. The RA patients were categorized based on rheumatoid factor (RF) seropositivity or seronegativity and the RA severity. Chemiluminescent immunoassay and 10% hematocrit were used to check levels of vitamin 25(OH)D and ROS, respectively. ELISA was used for the detection of IL-21 in the plasma. The RA patients had a significantly reduced vitamin 25(OH)D level compared to the healthy controls. The IL-21 and ROS were however significantly increased in the RA patients compared to the controls. Further, the seropositive RF and the high RA severity patients had significant IL-21 and ROS increase in comparison with the seronegative RF and the low severity RA patients. Finally, IL-21 negatively correlated with vitamin 25(OH)D, but positively correlated with the ROS. This is the first investigation to confirm the relationship between IL-21 with vitamin 25(OH)D and the ROS among the RA patients. The findings indicate that vitamin 25(OH)D is reduced in the RA patients' serum. ROS and IL-21 are also associated with increased RA severity.

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

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.

Rheumatoid Arthritis from Easy to Complex Disease: From the "2022 GISEA International Symposium".

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium.

Association of Fc Gamma Receptor 3B Gene Copy Number Variation with Rheumatoid Arthritis Susceptibility.

Structural variations such as copy number variants (CNVs) have been associated with multiple autoimmune diseases. In this study, we explored the association of the Fc gamma receptor 3B gene (FCGR3B) copy number variation (CNV) with rheumatoid arthritis (RA) susceptibility and related serological traits in the Pakistani population. We also performed a meta-analysis of four published FCGR3B CNV studies along with the current study. A total of 927 subjects (597 RA cases, 330 healthy controls) were recruited from three rheumatology centers in Pakistan. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were measured in RA patients. FCGR3B copy number was assayed using the TaqMan® CN assay (Hs04211858_cn, Applied Biosystems, Foster City, CA, USA) and the copy number was estimated by using CopyCaller® software (version 2.1; Applied Biosystems, USA). Logistic regression was applied to calculate the odds ratio (OR) of RA risk associated with FCGR3B CNV using sex and age as covariates in R. Meta-analysis on four previously published studies and the current study was performed using the random-effect model. We observed a significant association between FCGR3B copy number &lt; 2 and RA susceptibility (OR = 1.53; 95% CI: 1.05 to 2.22; p = 0.0259) and anti-CCP seropositivity (OR 2.56; 95% CI: 1.34 to 4.89; p = 0.0045). A non-significant association of FCGR3B copy number &lt; 2 was also observed between increased rheumatoid factor (RF) seropositivity (OR = 1.74; 95% CI:0.93 to 3.26; p = 0.0816). Meta-analysis on 13,915 subjects (7005 RA cases and 6907 controls) also showed significant association of copy number &lt; 2 with the increased risk of RA (OR = 1.30; 95% CI: 1.07 to 1.56; p = 0.00671). FCGR3B copy number &lt; 2 is associated with increased RA risk and anti-CCP seropositivity.

Influence of periodontitis on levels of autoantibodies in rheumatoid arthritis patients: A systematic review.

Periodontitis (PD) is a dysbiotic disease of tooth-supporting structures that has been associated with various systemic diseases including rheumatoid arthritis (RA). To date, evidence demonstrated increased prevalence of RA among PD patients and postulated PD to have a role in the development of autoantibodies in RA patients. Therefore, a systematic review was conducted to assess the available evidence to ascertain the effect of PD on levels of autoantibodies in the serum, saliva and gingival crevicular fluid (GCF) of RA patients. The systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Relevant literature was searched from PubMed, Web of Science, Scopus and Ebscohost databases from inception until 31 August 2020. The risk of bias in each study was determined based on the Newcastle-Ottawa Scale tool. Results from random-effect meta-analyses were presented as summary estimates of odds ratios (ORs) for seropositivity and standardised mean difference (SMD) of autoantibody levels with 95% confidence intervals. Sensitivity tests and meta-regression were performed to assess the robustness of the results and potential cause of heterogeneity. The electronic and manual searches gathered 932 articles. Following screening and full-text assessment, a total of 29 studies were included in the analysis. Twenty-eight published observational studies were included in the quantitative analysis in the form of random-effect meta-analysis which revealed that PD was associated with anti-citrullinated proteins autoantibodies (ACPAs) and Rheumatoid Factor (RF) seropositive RA patients (OR for ACPA seropositivity: 1.82; 95% CI: 1.13-2.93) (OR for RF seropositivity: 1.53; 95% CI: 1.05-2.24). Also, RA patients with PD had increased serum levels of ACPA and RF. However, high heterogeneity among studies' results, partially ascribed to the unstandardised case definition of PD and laboratory testing of autoantibodies. Apart from ACPA and RF in serum, studies which reported on other RA-related autoantibodies, as well as autoantibody levels in saliva and GCF were scarce. RA patients with PD tend to have greater ACPA and RF levels in their serum when compared with the RA patients without PD supporting the plausible role of PD in the development of systemic autoimmunity in RA patients.

Rheum-CoV-2 Vaccination Case Series.

In this case series, we present 5 cases of autoimmune rheumatic disease onset shortly after receiving mRNA vaccination against coronavirus disease 2019 (COVID-19). We identified 5 patients from Brooke Army Medical Center who developed new manifestations of rheumatic disease following the second dose of the Pfizer-BioNTech or Moderna COVID-19 vaccinations. All patients were initially seen in primary care and then referred to rheumatology for further evaluation and management. Clinical data were obtained through review of the electronic medical record. Three cases involve elderly women with insidious onset of symmetric wrist and hand polyarthritis with seropositivity for rheumatoid factor. One case involves an elderly woman with a subacute onset of lower extremity-predominant, symmetric polyarthritis. One case involves an elderly man with insidious onset of bilateral shoulder and hip stiffness and arthralgias in the setting of elevated erythrocyte sedimentation rate and a rapid response to glucocorticoid therapy. Whether there exists a causal or contributory relationship between COVID-19 mRNA vaccination and the development of autoimmune rheumatic disease remains to be determined. Ultimately, further research is needed to establish if there is a true connection between the two.

Prevalence, Clinical Manifestations, and Treatment Pattern of Patients with Rheumatoid Arthritis Attending the Rheumatology Clinic at Tikur Anbessa Specialized Hospital, Ethiopia: A Cross-Sectional Study.

BackgroundRheumatoid arthritis (RA) is an a chronic inflammatory disease characterized by symmetric polyarticular inflammation that can lead to progressive joint damage. It is said to be rare among black Africans, even though there have been limited reports from some African countries and no study has been done on RA in Ethiopia. This study determined the prevalence, clinical features, and treatment of rheumatoid arthritis in Tikur Anbessa Specialized Hospital (TASH).MethodsA cross-sectional study design was conducted on diagnosed patients with RA attending the rheumatology clinic at TASH from November 2018 to February 2019. Data was collected through patient interviews and chart reviews. The dataset was subjected to descriptive statistical analysis using the Statistical Package for Social Sciences (SPSS) version 25.ResultsA total of 1116 patients attended a rheumatologic clinic with rheumatologic complaints. The prevalence of rheumatoid arthritis was 18.5% (206/1116). Females were mostly affected (F:M 4.6:1). One hundred nineteen (57.8%) were between 35 and 64 years of age. The seropositivity for rheumatoid factor was 47.1%. Almost all patients had morning stiffness (89.8%) and joint pain (97.1%), with the majority (74.8%) having both small and large joint involvement. Nearly half of the patients, 99 (48.1%), had a joint deformity. Comorbid conditions seen in this study were hypertension (17%), overweight in 43 (20.9%), and obesity in 8 (3.9%). Methotrexate was the most prescribed agent (82.5%), both as monotherapy and along with other medications, but 139 (67.5%) of them were on prednisolone, which 2/3 (122) of patients took for 6 months in duration.ConclusionRA accounted for nearly one-fifth of the patients coming to the rheumatology clinics, with females affected more, which is similar to reports from some African countries. Disease-modifying anti-rheumatic drugs are the most prescribed agents, but most patients are on a prolonged dose of prednisolone.

Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA.MethodsA total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4+, CD19+ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( −) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA).ResultsPatients with RA had higher percentages of CD4+ T, CD19+ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF+ or ACPA+ patients exhibited elevated percentages of CD19+ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF−/ACPA− and RF+/ACPA+ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different.ConclusionTh17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA.Key Points• Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages.• No difference for the distribution of Th17, Treg, and ILC subsets between RF+and RF− patients and between ACPA+and ACPA− patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.

Prevalence of antinuclear antibodies and rheumatoid factor titers in dogs with arthritis secondary to leishmaniosis (Leishmania infantum).

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose-Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

OA15 Drivers of change in four and two component disease activity scores after etanercept treatment, in a multi-centre cohort of patients with established rheumatoid arthritis

Abstract Background/Aims Treatment response in RA is measured by different disease activity scores (DAS28). The widely used 4 component (4C) DAS28 does not always correlate with synovitis, and a new 2 component version (2C) DAS28 has been developed to address this problem. Here, we use multivariable linear regression models to identify drives of change (Δ) in 4C and 2C DAS28 after 3 months on the anti-TNF drug etanercept (ETN). Methods Using data from the Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS), we identified patients treated with originator or biosimilar ETN (N = 773). Differences between the follow-up (FU) and baseline (BL) DAS28, adjusted for baseline, serve as outcome variables. Multiple imputation by chained equations was used to impute missing data, and models were internally validated via bootstrapping. Table 1 shows the baseline statistics, and model parameters for the included covariates. Results We found that 15.8% (95% CI: 11 - 20.6%) of the variance in Δ4C was explained by the baseline DAS28, compared to 26.3% (95% CI: 20.9 - 31.7%) for the Δ2C. Age of onset, HAQ score and concurrent DMARD treatment were significantly associated with both ΔDAS28 scores. Δ4C-DAS28 was additionally associated with first biologic use, seropositivity for either rheumatoid factor or anti-citrullinated peptide antibodies, and the Hospital Anxiety and Depression Scale-Anxiety score. The only additional predictor significantly associated with Δ2C-DAS28 was weight. After adjusting for baseline DAS28, the additional clinical covariates only explained 7.6% (IQR: 7.3 - 7.8%), and 2.3% (IQR: 2.0 - 2.6%) of the variance for the 4C- and 2C-DAS28, respectively. Conclusion ΔDAS28 is heavily influenced by the baseline DAS28, and additional clinical covariates explain little to none of the additional variance. Notably, known factors associated with treatment response, such as seropositivity and previous unsuccessful treatments, were only significant for the 4C-DAS28. This suggests that the 4C DAS and 2C DAS capture different aspects of RA disease progression. Further association studies are required to find other reliable predictors for ΔDAS28, which may include biological markers of response. Significant covariates identified here should be considered as potential confounding factors. Disclosure M. Stadler: None. S. Ling: None. N. Nair: None. J. Isaacs: None. K. Hyrich: None. A. Morgan: None. G. Wilson: None. D. Plant: None. J. Bowes: None. A. Barton: None.

Presence of Autoantibodies in Males and Females With Rheumatoid Arthritis: A Systematic Review and Metaanalysis.

Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity. Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28). Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77-0.91] for RF and OR 0.88 [95% CI 0.81-0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity. Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.

Erosive Hand OsteoArthritis (EHOA): analysis of consecutive patients presenting with EHOA in a hospital-based rheumatology practice and its implications for an upcoming interventional study.

Erosive Hand OsteoArthritis (EHOA) is a common rheumatological problem. We aim to determine characteristics of EHOA patients: comorbidities, radiographic erosivity and pain experienced after being diagnosed, in order to find which of these are potentially relevant in upcoming interventional trials. Retrospective analysis of EHOA patients within the electronic database in one centre, with a telephone interview on pain as experienced even exceeding 12months after being diagnosed. Eighty-four non-academic EHOA patients were found: 89% females (median age 69years), 11% males (similar age distribution). Kellgren-Lawrence (KL) erosivity scores in both sexes were comparable; DIPs scored higher than PIP's. Comorbid conditions were crystal-induced arthritis, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in 8%, 5% and 1%, respectively; seropositivity for rheumatoid factor and anti-citrullinated protein antibodies in 8% and 1% respectively. Pain worst experienced often exceeded a visual analogue score of 5.0, but was unrelated to the total KL score. Some pain reduction was reached with non-steroidals (perorally/transcutaneously) as deduced from continued use in 1 in 3. In many EHOA patients, there is an unmet need regarding the treatment of pain, which per se was not directly correlated with erosivity score. Future studies may be designed considering the aforementioned characteristics, acting on the inflammatory process resulting in PIP/DIP erosions, with the exclusion of RA and PsA in order to get a clean study on EHOA. Several studies with monoclonal antibodies have been performed but demonstrated ineffectivity on the outcome of pain. Hope glooms with the arrival of innovative small molecules that may reach EHOA target cells. Key Points • Erosive handOA is a common problem in non-academic rheumatology; it is often associated with significant pain in both sexes exceeding a VASpain of 5.0 even years after being diagnosed; 1 in 3 found some relief in non-steroidals perorally/transcutaneously. • Future studies will have to focus on (episodic) inflammatory hand OA resulting in proven erosivity (EHOA) located in PIP plus DIP joints and may have to exclude comorbid active crystal-induced arthritis as well as rheumatoid/psoriatic arthritis and possibly even RF/ACPA seropositivity in order to get a clean study on EHOA. • As several big monoclonals have failed in EHOA, we may have to search for promising new drugs within the group of small molecules. These will have to show a significant pain-reducing effect and preferably also a disease-modifying osteoarthritis drug (DMOAD) effect.

High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1–6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.

INTERSTITIAL LUNG DISEASE AS THE ONLY MANIFESTATION OF RHEUMATOID ARTHRITIS: CAN LUNGS BE THE SITE OF ORIGIN FOR RHEUMATOID ARTHRITIS-RELATED INFLAMMATION?

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease primarily involving joints. Extra-articular manifestations of RA without joint disease are extremely rare. Lung disease represents a second common cause of death in RA after cardiovascular events (1). RA related lung disease includes interstitial lung disease (ILD), bronchiectasis and pleural disease. We report a patient with severe progressive RA related ILD, usual interstitial pneumonia (UIP) phenotype without joint involvement and poor outcome. CASE PRESENTATION: A 67-year-old female with one-year history of seropositive rheumatoid arthritis without joint involvement, on methotrexate presented with worsening shortness of breath. The exertional dyspnea started two years ago, and a screening low dose CT chest showed mild fibrotic changes at lung bases prior to methotrexate initiation. This time HRCT revealed progressive interstitial lung disease-usual interstitial pneumonia pattern, bilateral honeycombing of the lung bases and traction bronchiectasis. Pulmonary function test revealed restrictive ventilatory and severe gas transfer defect. Rheumatoid factor (RF) and Cyclic Citrullinated Peptide antibody (IgG) were 99.6 and above 250 respectively. ANA titer was low at 1:40, speckled pattern with normal ANCA. Methotrexate was discontinued and prednisone was started. She was discharged home on oxygen therapy but continued to decompensate with progressive hypoxemic respiratory failure eventually requiring high flow nasal canula. Repeat HRCT showed new ground glass opacities on left along with baseline interstitial changes. Flexible bronchoscopy with bronchoalveolar lavage showed no evidence of infection or malignancy. Patient was started on pulse dose steroids for possible ILD flare. However, her oxygen requirement and symptoms continued to worsen, and she was started on Mycophenolate Mofetil. With no improvement patient eventually opted for home hospice. DISCUSSION: Risk factors associated with RA-related ILD include older age, male sex, smoking and seropositivity for RF or anti-CCP antibodies. In addition, women with seropositive RA have increased risk of lung involvement than women without RA (2). Our patient presented with rapidly progressive ILD-UIP type without any joint disease and poor outcome. Methotrexate was less likely a culprit given the interstitial fibrotic changes present before drug initiation and rapid progression of ILD despite drug cessation. In our case lungs seem to be the primary site of RA related inflammation in setting of smoking causing citrullination of proteins and autoimmune responses (2). CONCLUSIONS: Although data on identification, management staging or monitoring of RA-related ILD without joint disease is lacking, clinicians should remain vigilant of this complication. RA-related UIP is more frequent with progressive disease and poor outcome and warrants early recognition and treatment (3). REFERENCE #1: G. Cafaro, A. Alunno, V. Valentini, M.C. Leone, E. Marcucci, E. Bartoloni, R. Gerli. The onset of rheumatoid arthritis: the joints or the lung? Reumatismo, 2016; 68 (4): 167-175 REFERENCE #2: Paolo Spagnolo, Joyce S. Lee, Nicola Sverzellati, Giulio Rossi, Vincent Cottin. The lung in Rheumatoid Arthritis. Focus on Interstitial Lung Disease. ARTHRITIS & RHEUMATOLOGY Vol. 70, No. 10, October 2018, pp 1544-1554 DOI 10.1002/art.40574 American College of Rheumatology REFERENCE #3: Hyun-Kyung Lee, MD; Dong Soon Kim, MD; Bin Yoo, MD; Joon Beom Seo, MD; Jae-Yoon Rho, MD; Thomas V. Colby, MD; Masanori Kitaichi, MD. Histopathologic Pattern and Clinical Features of Rheumatoid Arthritis-Associated Interstitial Lung Disease (CHEST 2005; 127:2019-2027) DISCLOSURES: No relevant relationships by Maria Azhar, source=Web Response No relevant relationships by Fatima Halilu, source=Web Response No relevant relationships by Qasim Muhammad, source=Web Response No relevant relationships by Matthew Woodford, source=Web Response

Evaluation of the effectiveness of Tofacitinib in rheumatoid arthritis in real clinical practice: The relationship between pain relief in the first 4 weeks and disease activity after 3–6 months

The JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the studywas to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods.The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results.The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI&gt;40), 15.9% had NCP (PainDETECT&gt;18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p&lt;0.05) and CS – 40.4±13.5 to 36.5±12.5 according to CSI (p=0.01). After 28 days, the effect was even more significant: the level of pain according to the VAS was 2.8±1.6 (p=0.000), the NCP decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CS – up to 31.6±13.9 (p=0.000). The value of the DAS28-CRP index after 3 and 6 months was 3.7±1.3 and 3.6±1.2, respectively. The number of patients with pain relief ≥50% after 28 days was 59.9%, low RA activity after 3 months. (DAS28-CRP≤3.2) was acieved in 64.4% of patients. There was a clear correlation between the number of patients with a pain reduction of ≥50% at 28 days and the number of patients who achieved low RA activity at 3 and 6 months. (rS=0.548, p=0.000 and rS=0.790, p=0.000). 6 patients dropped out of the study due to inefficiency or social reasons. No serious adverse reactions were noted.Conclusions.The use of the JAK inhibitor TOFA allows achieving a quick analgesic effect and reducing the signs of CS. An early clinical response to TOFA (pain relief) predicts a decrease in RA activity after 3 and 6 months of therapy.