Disease Activity Score-erythrocyte Sedimentation Rate Research Articles

Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis.

AimThe cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pathophysiology of rheumatoid arthritis (RA). The goal of this study was to evaluate the role of serum TNF-α as a competent biomarker of disease activity in RA and to assess the correlation of serum TNF-α with DAS28-ESR (disease activity score-erythrocyte sedimentation rate in 28 joints) and other markers expressed in serum of RA patients.MethodologyThe study was conducted from May 2020 to October 2020 after approval from the Ethical Review Committee of Ziauddin University. This cross-sectional study included 90 diagnosed cases of RA from 30 to 65 years with the complaint of arthralgia. Patients from the rheumatology clinic were enrolled in the study by a non-probability consecutive sampling technique. Informed consent was taken from each patient and they were assessed through a set of questions based upon disability in the performance of daily activities due to RA. Evaluation of serum levels of anti-cyclic citrullinated peptide (ACCP), rheumatoid factor (RF), erythrocyte sedimentation rate, and TNF-α were done by enzyme-linked immunosorbent assay (ELISA). Patients were segregated into groups based upon DAS28-ESR with erythrocyte sedimentation rate as an inflammatory marker. The Kruskal Wallis test was applied for the comparison of different variables in these groups. Spearman correlation was applied for the association between different variables. Multiple variable analysis was performed to assess the predictability of disease activity by serum markers included in the study.ResultsThe results of our study disclosed a significant difference in ACCP, TNF-α, tender joint count of 28 joints (TJ-28), swollen joint count of 28 joints (SJ-28), and health assessment questionnaire-disability index (HAQ-DI) in disease activity groups. A significant correlation of serum TNF-α with DAS28-ESR in RA patients was observed.ConclusionThis study illustrated a significant correlation of serum TNF-α with DAS28-ESR in RA patients. We found that expression of serum TNF-α may intensify the inflammatory activity in early RA, therefore, RA patients must be screened for this cytokine to monitor that disease activity could be useful for patients undergoing anti-TNF therapy.

POS0513 ABATACEPT IN MONOTHERAPY VERSUS COMBINED IN INTERSTITIAL LUNG DISEASE OF RHEUMATOID ARTHRITIS. MULTICENTER STUDY OF 263 CAUCASIAN PATIENTS

Background:Interstitial lung disease (ILD) is a severe complication of RA. Abatacept (ABA) have demonstrated efficacy in RA-ILD [1,2], although combined treatment with MTX or others DMARDs remain controversial.Objectives:To assess the efficacy and safety of ABA in monotherapy (ABAMONO) versus combined-ABA, ABA plus MTX(ABAMTX) or ABA plus other non-MTX DMARDs (ABANON-MTX), in RA-ILD.Methods:Observational multicenter study of RA-ILD caucasian patients treated with ABA. We analyzed in three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcomes: a) Dyspnea, b) FVC and DLCO, c) HRCT, d) DAS28-ESR, e) corticosteroid-sparing effect. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used between the three groups.Results:We studied 263 RA-ILD patients (mean age 64.6±10 years) [ABAMONO (n=111), ABAMTX (n=46) and ABANON-MTX (n=106)]. At baseline, ABAMONO patients were older (67±10 years) and took higher prednisone dose (10 [IQR 5-15] mg/day). There was no statistically significant differences in sex, seropositivity, ILD patterns, FVC, DLCO or disease duration. In all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnea, HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in corticosteroid-sparing effect in ABAMTX or ABANON-MTX(Figure 1). However, in the multivariable analysis, there were no differences in any outcome between the three groups(Table 1).Table 1.Effect in FVC, DLCO, dyspnea (mMRC) and HRCT pulmonary scan after abatacept.ABAMONON=111ABAMTXN=46ABANON-MTXN=106ABAMTXvs ABAMONOABANON-MTXvs ABAMONOpppp*UnadjustedAdjusted**UnadjustedAdjusted**Follow-up, median [IQR] months12 [6-36]12 [6-36]18[12-36]0.400.670.17Differences between basal and final follow-upFVC, %-0.5 (-2.5, 1.5)0.641.2(-0.6, 3.1)0.17-1.2 (-2.9, 0.5)0.170.330.300.390.590.90DLCO, %1.8 (-0.7, 4.34)0.160.5 (-3.8, 4.8)0.82-1.5 (-4.1, 1.1)0.260.200.580.800.070.32mMRC, n (%)Worsening5 (5)3 (8)5 (5)0.830.470.99Stable or improving93 (95)36 (92)87 (95)HRCT pulmonary scan, n (%)Worsening13 (28)2 (11)15 (25)0.240.100.78Stable or improving34 (72)19 (89)44 (75)DAS28-ESR-1.5 (-1.9, -1.0)0.000-1.2 (-1.8, -0.6)0.000-1.5 (-1.8, -1.2)0.0000.740.580.92Prednisone, mg/day-3.8 (-8.3, 0.8)0.10-2.7 (-4.6, -0.8)0.006-4.8 (-6.3, -3.4)0.0000.690.670.65Differences in DAS28-ESR, prednisone, FVC and DLCO are expressed as mean difference (95%CI) comparing final follow-up minus basal values.*Differences between the 3 groups.**Differences between ABAMTX vs. ABAMONO, and between ABANON-MTX vs ABAMONO are adjusted for age, disease duration until abatacept treatment, and DAS28 and prednisone dose at baseline.Abbreviations(DAS28-ESR: Disease activity score-erythrocyte sedimentation rate; DLCO: Carbon Monoxide Diffusing Capacity; HRCT: High resolution computed tomography; FVC: Forced vital capacity, mMRC: modified Medical Research Council scaleFigure 1.Conclusion:In caucasian individuals with RA-ILD, ABAMONO or ABAMTX or ABANON-MTX seems to be equally effective and safe. However, a corticosteroid-sparing effect is only observed in combined-ABA.

POS0614 PERFUSE: A FRENCH PROSPECTIVE/RETROSPECTIVE NONINTERVENTIONAL COHORT STUDY OF INFLIXIMAB-NAÏVE AND TRANSITIONED PATIENTS RECEIVING INFLIXIMAB BIOSIMILAR SB2; 12-MONTH ANALYSIS

Background:SB2 is approved in the EU as an infliximab (IFX) biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the reference. PERFUSE is an ongoing non-interventional study of 1233 patients (496 with rheumatology diagnoses, 737 with gastroenterology diagnoses) receiving SB2 as routine therapy.Objectives:The aim of the study is to provide data on long-term outcomes in patients initiating SB2 in the real-world setting.Methods:Adult patients eligible for inclusion in the rheumatology study cohorts have a diagnosis of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Axial Spondyloarthritis (axSpA) and had initiated SB2 in routine clinical practice after September 2017, either as their first IFX or transitioning from treatment with IFX reference or another IFX biosimilar. Outcome measures include SB2 dose, disease activity scores and persistence on SB2, over time and up to 24 months after initiation. This interim analysis is the first complete analysis of 12 month data on all rheumatology patients enrolled into the study at 9 specialist sites and followed up to the data extract date of 29th October 2020. The analysis provides an overview of baseline characteristics, disease scores, SB2 dose and persistence at 12 months post-initiation of SB2.Results:Table 1.Mean Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) over the course of ICHIBAN. BL, baseline; SD, standard deviation.axSpA cohort(N=336;IFX naïve 81, IFX-prior 255)RA cohort(N=98;IFX naïve 22, IFX-prior 76)PsA cohort(N=62;IFX naïve 14, IFX-prior 48)Baseline characteristicsAge in years, mean (SD):IFX-naïve43.1 (11.1)53.1 (15.9)48.5 (12.2)Transitioned from IFX48.9 (12.4)57.3 (13.1)53.1 (13.0)Disease duration in years, mean (SD):IFX-naïve7.2 (9.3)11.3 (9.8)4.2 (3.9)Transitioned from IFX16.6 (11.6)17.3 (8.8)12.9 (11.3)Women, n (%):IFX-naïve26 (32.1)16 (72.7)6 (42.9)Transitioned from IFX79 (31.0)60 (78.9)15 (31.3)SB2 Dose: n, mean mg/kg (SD)IFX-naïve:Baseline81383.8 (85.5)22266.2 (145.9)14395.4 (108.9)Month 1247436.8 (153.3)13285.5 (90.7)6508.0 (147.6)Transitioned from IFX:Baseline255396.7 (109.6)76291.8 (103.4)48408.5 (91.3)Month 12195392.1 (105.5)60287.8 (106.6)41421.4 (101.6)Disease score, mean (SD)IFX-naïve:nBASDAInDAS28nDAS28Baseline545.8 (2.1)144.3 (1.6)-*-*Month 12303.5 (2.7)93.2 (1.2)Transitioned from IFX:Baseline2063.0 (2.0)622.6 (1.2)202.2 (1.2)Month 121513.0 (2.1)472.7 (1.2)192.1 (0.9)KM estimate of persistence on SB2 by Month 12; proportion, (95% CI)IFX-naïve56.26 (44.43; 66.51)59.09 (36.10; 76.21)64.29 (34.33; 83.31)Transitioned from IFX79.86 (74.37; 84.30)80.26 (69.42; 87.60)85.04 (71.11; 92.58)*Blank as disease score data for both baseline and Month 12 were provided by a single patient who was IFX-naïve and had PsA; IFX = infliximab; axSpA = Axial Spondyloarthritis; RA = Rheumatoid Arthritis; PsA = Psoriatic Arthritis; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; DAS28 = Disease Activity Score 28; CI = confidence interval; SD = standard deviation; KM = Kaplan Meier.Conclusion:This 12-month analysis indicates that patients with axSpA or RA can be successfully initiated on SB2 as the first infliximab therapy, and patients with axSpA, RA or PsA can be transitioned from originator or biosimilar IFX to SB2 without loss of disease control and with no dose penalty over 12 months post-transition. Over 56% of IFX- naïve patients and over 79% of patients transitioned from prior IFX remained on SB2 at 12 months post-initiation. With follow-up of patients ongoing to 24 months post-initiation of SB2, the study will continue to provide pertinent information about clinical outcomes of initiation on SB2 as first IFX or after transition from reference or IFX biosimilar to SB2.Acknowledgements:Data management for the study was provided by Sanoïa E-health services, Digital CRO, Gémenos, France; funding was provided by Biogen International GmbH.Disclosure of Interests:Bruno Fautrel Speakers bureau: AbbVie, Biogen, Boehringer-Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB., Consultant of: AbbVie, Biogen, Boehringer-Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB., Grant/research support from: AbbVie, MSD, Pfizer., Yoram Bouhnik Speakers bureau: AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB, Vifor Pharma., Consultant of: AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB, Vifor Pharma., Maxime Dougados Grant/research support from: Biogen, Ulrich Freudensprung Shareholder of: Biogen, Employee of: Biogen, Janet Addison Shareholder of: Biogen, Employee of: Biogen

The characteristics and its contributing factors of refractory rheumatoid arthritis, view of the rheumatologists of China: results of a nationwide cross-sectional survey.

To explore the characteristics of refractory RA and its contributory factors based on the understanding of the rheumatologists of China. A national cross-sectional survey was performed in 32 provinces across China, and 1381 rheumatologists were recruited. Information about the sociodemographic background, refractory RA characteristics, and contributory factors was collected using a pre-made questionnaire including fourteen single-choice and four multiple-choice questions, respectively. Each of the single-choice and multiple-choice question had several items. In response to the single-choice questions regarding the definition of refractory RA, 52.28% responded that "the 28 joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) > 5.1 with presence of signs suggestive of inflammatory disease" is characteristic of refractory RA, whereas 50.18% opined that "If target was not achieved with 2 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combined with 1 biological or 1 targeted synthetic DMARD (b/tsDMARD), over a total of 3~6 months" should be considered refractory RA. In addition, 39.32% rheumatologists were in favor of inability to taper glucocorticoids (GCs) ≤ 10mg prednisone or equivalent daily. Additional features considered characteristics of refractory RA were extra-articular manifestations (84.94%), interfering comorbidities (76.32%), and radiographic progression (71.83%). Among the contributory factors, 92.03% considered infection, and interstitial lung disease was chosen by 90.95%, vasculitis by 82.26%, osteoporosis by 70.67%, and fibromyalgia syndrome by 70.38%. Our survey has demonstrated a variety of concepts of refractory RA among the rheumatologists of China. Disease activity assessment, treatment options, interfering comorbidities, and radiological progression all were associated with the characteristics of refractory RA. Key Points • This study demonstrated the definition, characteristics, and contributing factors of refractory RA from the rheumatologists' views in China. • The clarification of the insights and concepts on refractory RA will help to make comprehensive guidelines to treat this disease, further improving prognosis and reducing the societal burdens of RA.

Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis.

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the “treatment in the Rotterdam Early Arthritis CoHort” (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68–0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67–0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61–0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression’s sensitivity significantly dropped from 83% to 69% (p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response.

A prospective, randomized, single-center, two-arm, open-label study to evaluate the efficacy of biotherapi®, a two-strain bacillus probiotic blend, as an adjunctive therapy in the treatment of rheumatoid arthritis

Objective: Probiotics have been shown to alleviate the symptoms of rheumatoid arthritis (RA) by normalizing the composition of gut microbiota. The objective of this study was to evaluate the effect of twice-daily Biotherapi® (Sanzyme Private Limited, India) as an adjunct to standard of care on disease activity and functional ability of patients with RA.Methods: In this prospective, randomized, single-center, two-arm, open-label study, patients were randomized (1:1) to receive twice-daily adjunctive Biotherapi® (n = 125) or standard of care alone (n = 125) for 12 weeks. The primary endpoint was the change from baseline to days 45 and 90 in the Disease Activity Score-28-erythrocyte sedimentation rate (DAS-28-ESR).Results: Standard of care alone and adjunctive Biotherapi® significantly reduced the mean DAS-28-ESR at days 45 and 90 (P < 0.05). However, the reduction from baseline was greater in patients receiving adjunctive Biotherapi® compared to standard of care alone at day 45 (–0.67 ± 0.77 vs. −0.15 ± 0.84, P < 0.0001) and day 90 (–1.21 ± 0.99 vs. –0.48 ± 0.69, P < 0.0001). Consequently, compared to standard of care, more patients achieved remission (4.3% vs. 23.6%) and showed good (6.52% vs. 35.45%) and moderate (31.5% vs. 41.81%) European League Against Rheumatism response at 90-day Biotherapi®. A similar pattern of improvement in the scores including Health Assessment Questionnaire was observed. No clinically significant changes in the laboratory parameters were reported during the study.Conclusion: Twice-daily supplementation with Biotherapi® probiotic blend as an adjunct to standard-of-care treatment for RA is beneficial for alleviation of severity and symptoms of the disease and results in improvement in patients' quality of life.

US7 score in the subacute phase does not correlate with outcomes in Chikungunya arthritis

Introduction: Chikungunya fever is a remerging disease and may lead to postchikungunya inflammatory joint pain. Objective: To study the clinical and ultrasound (US) features of chikungunya arthritis in the subacute phase and to determine if high disease activity on US on is associated with chronic disability. Materials and Methods: We conducted a prospective observational study of all patients who presented with subacute chikungunya arthritis over 1 year duration. Chikungunya fever was diagnosed by consistent clinical picture with specific immunoglobulin M positivity. Disease activity assessments and US-7 score were performed at baseline. Indian Health Assessment Questionnaire (HAQ) and pain on numerical rating scale were done at baseline and 1 year of follow-up. Results: We included 23 patients (18 females) with a median age of 43 years. Most (22/23) patients had polyarticular disease with negative rheumatoid factor and anticyclic citrullinated peptide. Ultrasound revealed synovitis in all and tenosynovitis in most patients. The median (interquartile range) US7 score, Disease Activity Score 28 erythrocyte sedimentation rate (DAS28-ESR) score, Indian HAQ, and pain at presentation were 15 (11), 4.4 (2), 0.92 (0.7), and 5 (6), respectively. Twenty patients were treated with a short course of glucocorticoids. One-year follow-up was available in 20 patients. The median HAQ and pain score at follow-up were 0.08 (0.21) and 1 (1), respectively . No correlation was found between US7 score, DAS28, swollen joint count, tender joint count, ESR, HAQ score, or pain at presentation with HAQ and pain at follow-up. Conclusion: Disease activity at presentation as assessed by US7 score did not correlate with disability and pain at 1 year of follow-up in patients with chikungunya arthritis.

Expression of two long noncoding ribonucleic acids (growth arrest-specific 5 and H19) in rheumatoid arthritis patients: Relation to clinical characteristics and disease activity

Background: Rheumatoid arthritis (RA) is a relatively common autoimmune disease in which genetic risk factors are well defined. Genetic studies are promising in exploring the long noncoding ribonucleic acids (lncRNAs): growth arrest-specific 5 (GAS5) and H19, and their possible role in the assessment of RA. Aim of the Work: The aim of the study was to describe the expression of GAS5 and H19 in serum samples of Egyptian RA patients in comparison to healthy controls, then to investigate its possible relation to RA clinical characteristics and disease activity. Patients and Methods: Levels of GAS5 and H19 expression were compared in serum samples from Egyptian RA patients (n = 100) and age- and sex-matched healthy controls (n = 100) and then correlated within the RA group to disease activity measured by the Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR). Results: GAS5 was downregulated (0.59 ± 0.36), while H19 was upregulated (7.41 ± 1.3) in sera of Egyptian RA patients in comparison with controls (1.07 ± 0.09 and 1.1 ± 0.09 respectively). Further analysis showed a significant negative correlation of GAS5 to DAS28-ESR (r = -0.380). However, H19 showed a positive correlation to DAS28-ESR (r = 0.487 (P Conclusion: GAS5 was related to less disease activity, while H19 tended to be associated with more active disease. They might be useful in RA as potential biomarkers for disease activity assessment in the following years. Still, further researches are needed to support our findings and precisely determine their potential utility in RA.

Serum Levels of Beta-2 Microglobulin in Rheumatoid Arthritis Patients and its Relationship with Disease Activity: Can it be used as a Disease Activity Marker?

Abstract Background Beta-2 microglobulin (β2M) is mainly released from activated lymphocytes. Increased serum β2M levels have been shown in autoimmune diseases. The aim of this study was to analyse the serum levels of β2M in rheumatoid arthritis (RA) patients and to evaluate its relationship with disease activity measures. Material and Methods This cross-sectional study included 137 RA patients, 102 ankylosing spondylitis patients (AS) and 50 healthy controls (HC). To assess the disease activity of RA patients, the 28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR), the 28-joint Disease Activity Score-C-Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were used. A p value of &lt;0.05 was considered statistically significant. Results Serum β2M levels were significantly higher in RA patients (2.95±1.19 mg/L) compared with HC (2.21±0.54 mg/L) and AS patients (2.200.58 mg/L) (p&lt;0.001). There was a statistically significant correlation between β2M levels and DAS28-ESR (rs=0.359, p&lt;0.001), DAS28-CRP (rs=0.293, p=0.001), SDAI (rs=0.332, p&lt;0.001) and CDAI (rs=0.291, p=0.001). Serum β2M levels were higher in the RA group with DAS28-ESR ≥3.2 (3.30±1.42 mg/L) than in the DAS28-ESR &lt;3.2 group (2.67±0.87 mg/L) (p=0.002). Conclusion Our study revealed that serum β2M levels were higher in RA patients than in healthy controls, and, in contrast to other studies, we found positive correlations between β2M levels and RA disease activity measures.

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic...

Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

BackgroundThe aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset < 1 year) treated according to treat-to-target (T2T) therapy.MethodsBaseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined.ResultsA subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P < 0.05) and 3-year follow-up (r = 0.21, P < 0.05). Individual slopes of the relationship between DAS28-ESR and progression scores in each time interval were significantly correlated over time and the slope of the first 6 months was moderately associated with this slope at later time points (r between 0.39 and 0.59; P values < 0.001). Between 15.9 to 22.7% and 16.7 to 38.5% of patients with low and moderate time-integrated disease activity, respectively, experienced relevant (ΔSHS ≥ 3) radiographic progression at the different time intervals. Analyses using CRP showed similar results.ConclusionsIn early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years.Trial registrationNetherlands Trial Register NTR578, 12 January 2006.

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA).MethodsProspective non-randomised observational...

Cytokines (IL-15, IL-21, and IFN-γ) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.

Collection of antirheumatic medication data from both patients and rheumatologists shows strong agreement in a real-world clinical cohort: the Ontario Best Practices Research Initiative—a rheumatoid arthritis cohort

ObjectivesThe objective of the study was to examine the agreement between patient- and rheumatologist-reported antirheumatic medication (ARM) use in the Ontario Best Practices Research Initiative. Study Design and SettingWe included adult patients who enrolled on or after September 1st 2010 and compared ARM use where rheumatologist visits and interviews occurred within 60 days of each other. Kappa statistic was used to measure agreement. We calculated sensitivity, specificity, and positive and negative predictive value, considering patient-reported data as the gold standard. To examine factors associated with agreement, a hierarchical generalized linear model was used. A subset analysis was also completed to compare start and stop dates of ARM. ResultsOverall agreement for ARM was good with higher sensitivity and lower specificity for conventional synthetic disease-modifying antirheumatic drugs compared with biologic disease-modifying antirheumatic drugs. Increased Health Assessment Questionnaire pain index and 28 disease activity score–erythrocyte sedimentation rate (DAS28-ESR) were significantly associated with lower agreement. Reporting stop dates was higher (19.4%) for patient-reported data compared with rheumatologist-reported data (13.1%). ConclusionARM reports had strong agreement particularly for patients who have low disease activity and pain. ARM discontinuation was reported more frequently by patients, which may indicate that patients may be discontinuing use of their rheumatoid arthritis medications before consulting their rheumatologist.

Impact of yoga based mind-body intervention on systemic inflammatory markers and co-morbid depression in active Rheumatoid arthritis patients: A randomized controlled trial.

Recovery of patients with rheumatoid arthritis (RA) depends on several physical and psychological factors, besides pharmacological treatment. Co-morbid depression adversely affects the outcome in RA. Usual medical therapies have a limited scope and fail to cure the psychological component of the disease. With advanced therapeutic options, achieving a state of remission has become the treatment goal, yoga based mind body intervention (MBI) may provide a holistic approach in its treatment dimension. Hence, MBIs are the need of hour as majority of diseases have a psychosomatic component. To explore the effect of Yoga based MBI on disease specific inflammatory markers and depression severity in active RA patients on routine disease modifying anti-rheumatic drugs (DMARDs) therapy. A total of 72 RA patients were randomized into 2 groups: yoga group (yoga with DMARDs) and control group (DMARDs only). Blood samples were collected pre and post intervention for primary outcome measurements of systemic biomarkers. Disease activity score 28, erythrocyte sedimentation rate (DAS28ESR) and health assessment questionnaire disability index (HAQ-DI) were used to assess disease activity and functional status respectively at pre and post intervention time-points. Secondary outcome, depression severity, was assessed by Beck Depression Inventory II scale (BDI-II) at 2 weekly intervals during 8 weeks of the study interventional plan. After 8 weeks of yoga based MBI, there was significant decrease in the severity of RA as seen by reduction in levels of various systemic inflammatory markers as well as in DAS28ESR (p-value <0.0001; effect size = 0.210) and HAQ-DI (p-value 0.001; effect size = 0.159). Also, yoga group experienced a statistically significant time dependent step-wise decline in depression symptoms over the period of 8 weeks as compared to control group (p-value <0.0001; effect size = 0.5). Regression analysis showed greater reduction in the scores of BDI-II with DAS28ESR (R2 = 0.426; p < 0.0001) and HAQ-DI (R2 = 0.236; p = 0.003) in yoga group. Yoga, a mind body intervention re-established immunological tolerance by aiding remission at molecular and cellular level along with significant reduction in depression. Thus in this severe autoimmune inflammatory arthritis with a major psychosomatic component, yoga can be used as a complementary/adjunct therapy.

Age and quality of life in patients with rheumatoid arthritis treated with biologic agents

Objectives: This study aimed to assess the relationship between age and quality of life (QOL) in patients with rheumatoid arthritis (RA) after treatment with biologic agents.Methods: We recruited 153 patients with RA treated with biologic agents at three hospitals of Showa University from 2005 to 2016 for this retrospective cohort study. Patients were divided into two groups—aged 65 years and older (elderly group) and aged under 65 years (adult group). The primary outcome was the change in QOL over 6 months. We measured QOL using the Medical Outcomes Study Short-Form-36 (SF-36), the physical component scale (PCS), and the mental component scale (MCS).Results: There were 94 adult patients (61.4%) and 59 elderly patients (38.5%). Adjusted for sex, disease duration, Disease Activity Score 28 erythrocyte sedimentation rate (DAS28ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and complications including interstitial lung disease, diabetes mellitus, and chronic kidney disease, there was a significant difference in PCS changes in 6 months between the groups (regression coefficients −7.25; 95% Confidence Interval (CI) −11.7 to −2.77; p = .0018). There was no significant difference in MCS.Conclusion: Elderly patients with RA may have more difficulty in achieving a satisfactory QOL after treatment with biologic agents.

Relationship Between Health-Related Quality of Life and Patient Acceptable Symptom State With Disease Activity and Functional Status in Patients With Ankylosing Spondylitis in Thailand.

This study aimed to identify factors associated with EuroQoL-5 Dimensions, 5 Levels and Patient Acceptable Symptom State (PASS) and health utility (HU) in Thai patients with ankylosing spondylitis (AS). This was a cross-sectional study of consecutive AS patients visiting Siriraj Hospital between May 31, 2012, and March 31, 2016. Demographic data and outcomes related to HU (Thai version of EuroQoL-5 Dimensions, 5 Levels), disease activity (Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate or Ankylosing Spondylitis Disease Activity Score-C-reactive protein, number of tender and swollen joints, and enthesitis), and functional status (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire) were collected. Regression analysis was used to explore factors associated with each EuroQOL-5 Dimensions (EQ-5D) domain, HU, and PASS. Among 119 AS patients, the mean age was 40.4 years; 61.3% were male. The mean EQ-5D was 0.75. In univariate analysis, lower disease activity and less impaired function were significantly associated with higher HU and not to mild problems in each EQ-5D domain. In multivariate regression analysis, Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein, and Health Assessment Questionnaire adjusting for age explained 77.4% of the HU variance. Patients answering yes to PASS were significantly older, had higher HU, and lower disease activity compared with those answering no to PASS. Usual activity and pain problems were importantly related to PASS after adjusting for other domains and age. Disease activity and functional status in AS patients were significant factors related to HU and PASS. To improve quality of life, treatment goals should be achieving remission, improving function, and controlling pain.

Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune arthropathy characterized by synovial hyperplasia leading to functional impairment. Although the exact cause of RA is unknown, there is evidence suggesting the role of T cell subtypes in the pathogenesis of RA. Conventional therapy in some RA patients is associated with mild or severe side effects, and resistance of some patients has been reported to these types of therapy. The therapeutic potential of mesenchymal stem cells (MSCs) introduced them as a novel therapeutic choice for the treatment of rheumatic diseases. The aim of our study was to evaluate the effects of intravenous administration of autologous bone marrow-derived MSCs on the immunological, clinical and para-clinical factors such as regulatory T cells, Th17 cells, CD8+ T cells, CD4+ T cells, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), visual analogue scale (VAS), ESR, C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with refractory RA. Nine refractory RA patients with no other rheumatologic disorders were included in this study. All patients received a single intravenous dose of 1 × 106 autologous bone marrow-derived MSCs/kg, and were followed up at 1, 6 and 12 months after injection of MSCs. We found a significant decreasing trend in Th17 percentage and geometric mean fluorescence intensity for IL-17A following injection of MSCs at 12 months compared to the time point zero. Furthermore, a significant increase in regulatory T cells percentage was observed at the end of the first month after the intervention. DAS28-ESR decreased significantly at 1 and 12 months after MSC therapy. VAS score showed a significant decreasing trend during the follow-up periods. No significant difference was found for serum CRP and anti-CCP levels after the intervention. In conclusion, our data indicated that clinical symptoms were significantly ameliorated following the intravenous injection of autologous bone marrow-derived MSCs to the patients with refractory RA.

ENHO gene expression and serum adropin level in rheumatoid arthritis and systemic lupus erythematosus.

Adropin, a secreted protein, is encoded by the energy homeostasis-associated gene (ENHO). It is expressed by a variety of tissues and cells. It has been implicated in several physiological and pathological processes, such as angiogenesis and apoptosis. The aim of the present study was to investigate the ENHO gene expression and serum adropin levels in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The study included 36 patients with RA, 22 patients with SLE and 20 healthy controls (HC). Patients with a disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR) >2.6 in the RA group and an SLE disease activity index (SLEDAI) >6 in the SLE group were accepted as active. Serum adropin levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) method. The ENHO gene and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expressions in peripheral blood mononuclear cells were analyzed by real-time polymerase chain reaction (PCR). The ENHO gene mRNA expression was significantly higher in the RA group than in the HC group (p = 0.024), although it was similar between the SLE and HC groups (p = 0.920). On the other hand, there were no significant differences among the study groups in terms of serum adropin levels (p > 0.05 for all). Moreover, there was no significant difference in terms of the ENHO expression and serum adropin levels between active and inactive RA and SLE patients. Although the ENHO gene expression is increased, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases need to be tested by further studies.