High Disease Activity Patients Research Articles

High BMI is associated with lower TNF-α inhibitor serum trough levels and higher disease activity in patients with axial spondyloarthritis

BackgroundTNF-α inhibitor (TNFi) serum trough levels have previously been found to be related to disease activity in axial spondyloarthritis (axSpA). However, most research regarding serum trough levels has been conducted in patients who only recently started TNFi therapy. Therefore, our objective was to explore TNFi serum trough level measurements in relation to disease activity and BMI in the total axSpA population in daily clinical practice, also including patients on long-term TNFi therapy.MethodsConsecutive patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were approached for a TNFi serum trough level measurement during their regular outpatient visit at the UMCG. Spearman’s correlation coefficient was used to analyse the relation of serum trough levels with disease activity and BMI. Logistic regression was performed to analyse the relation between therapeutic drug levels and disease activity, corrected for potential confounders, including BMI.ResultsThirty-four patients on adalimumab and 21 patients on etanercept were included. Mean age was 45 ± 12 years, 47% were male, median BMI was 26.4 (IQR 23.9–32.5) and median treatment duration was 41 months (range 2–126). According to definitions of Sanquin, 47% of patients had therapeutic serum trough levels. No significant correlations were found between TNFi levels and disease activity (ASDAS-CRP: adalimumab: ρ = -0.16, p = 0.39; etanercept: ρ = -0.29, p = 0.20). TNFi levels were moderately correlated with BMI (adalimumab: ρ = -0.48, p = 0.004; etanercept: ρ = -0.50, p = 0.021). Patients with active disease (ASDAS ≥ 2.1) showed higher BMI than patients with inactive disease (median 29.7 vs. 24.6, p = 0.015). In multivariable regression analyses, BMI was identified as the only confounder for the relationship between therapeutic drug levels and ASDAS.ConclusionIn this cross-sectional, observational study of axSpA patients mainly on long-term treatment with TNFi, higher BMI was significantly associated with lower adalimumab and etanercept serum trough levels and higher disease activity.

E054 Rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan Region

Abstract Background/Aims In December 2019, a new type of novel coronavirus (COVID-19) was identified in Wuhan, China. The likelihood of developing an autoimmune and/or rheumatic diseases in COVID-19 survivors is high and a serious matter. The acute SARS-CoV-2 infection may unmask previously undiagnosed rheumatic conditions. We aimed to study rheumatic autoimmune disease manifestations diseases following COVID-19 infection survival. Methods The study was an observational case series study. The data collection was carried out in Iraqi Kurdistan region between the 1st of July 2021 and 20th of March 2022. Seventy-five patients were included: the patients who previously had confirmed COVID-19 infection who developed symptoms of rheumatic autoimmune diseases post COVID-19 cure. The study was conducted via a rigorous evaluation by two rheumatologists. Patients were investigated by (ESR (mm/h) and CRP (mg/L), some autoimmune screen panel for suspecting rheumatological disease patients were sent for ANA, anti-CCP (U/ML) and rheumatoid factor (IU/M) L. Then, patients were diagnosed according to the classification criteria for suspected autoimmune diseases and those with exacerbation were evaluated clinically and by laboratory; rheumatoid arthritis by DAS28, systemic lupus erythematosus by C3, C4. Results A total of seventy-five participants post-COVID-19 infection were enrolled in this study. Age of the participants was 47.15 ±16.18 SD, more of the participants were female (69) out of 75. For most of the patients the ESR were high with p value of 0.012, which was statistically significant. ANA was high titre in SLE patients which was (3.05±2.4) and in antiphospholipid syndrome p-value was significant at 0.042, Anti-CCP were positive in RA patients and in those with exacerbation of RA (44±10, 31.7±5.7 respectively), DAS28 was (4.95±0.59) moderate and high disease activity in patients with exacerbations. C3, C4 were low in patients with exacerbation of SLE (0.47±0.22, 0.03±0.01, respectively). Most of the patients developed symptoms post-COVID-19 between 4-10 weeks (37 participants). Conclusion Rheumatic autoimmune diseases presenting post-COVID-19 survival most commonly were systemic lupus erythematous followed by rheumatoid arthritis. and previous autoimmune diseases presented with exacerbation. Disclosure A.M. Jalal: None. N. Albarzinji: None.

Short communication: Differences in clinical outcomes according to the healthcare regime in Colombian patients with rheumatoid arthritis

Introduction/ObjectivesRheumatoid arthritis (RA) is a burdensome disease from both individual and societal perspectives, in which access to a rheumatologist plays a pivotal role in disease activity and reduction of its impact. We describe preliminary results of our study aimed at exploring whether healthcare regime affiliation influences disease outcomes of Colombian patients with RA. Materials and methodsWe performed a retrospective observational study of RA patients (2010 ACR/EULAR classification criteria) with at least 3 assessments in rheumatology clinics from different healthcare regimes: Contributory (CR), Subsidized (SR), a centre of clinical excellence (C3) that follows CR patients. We retrieved data from clinical charts including a follow-up period of 2 years. ResultsWe included one hundred and sixty patients (C3: 79 [49.4%], CR: 26 [16.2%], SR: 55 [34.2%]). Median initial age was 54 years (IQR 48–62) and most patients were women (77.8%). Of the patients, 79% had established RA and 70% had high disease activity at the beginning of the follow-up. We observed statistical differences between groups with regards to (1) median time to scheduled visits, (2) percentage of visits accomplished in scheduled time, (3) median time to real visit, (4) adherence, (5) median percentage of time in high disease activity, and (6) percentage of patients in high disease activity at the end of follow-up. The best outcomes were observed in the C3 cohort. ConclusionsAccess opportunity and clinical outcomes of Colombian patients with RA appear to differ between healthcare regimes. Although systematic bias may be present due to sample size, these data imply the healthcare regime is a major determinant of disease outcomes.

S100A8 and S100A12 Proteins as Biomarkers of High Disease Activity in Patients with Rheumatoid Arthritis That Can Be Regulated by Epigenetic Drugs.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that is still not well understood in terms of its pathogenesis and presents diagnostic and therapeutic challenges. Monocytes are key players in initiating and maintaining inflammation through the production of pro-inflammatory cytokines and S100 proteins in RA. This study aimed to test a specific DNA methylation inhibitor (RG108) and activator (budesonide) in the regulation of pro-inflammatory mediators-especially the S100 proteins. We also searched for new biomarkers of high disease activity in RA patients. RNA sequencing analysis of healthy controls (HCs) and RA monocytes was performed. Genes such as the S100 family, TNF, and IL-8 were validated by qRT-PCR following DNA-methylation-targeted drug treatment in a monocytic THP-1 cell line. The concentrations of the S100A8, S100A11, and S100A12 proteins in the sera and synovial fluids of RA patients were tested and correlated with clinical parameters. We demonstrated that RA monocytes had significantly increased levels of S100A8, S100A9, S100A11, S100A12, MYD88, JAK3, and IQGAP1 and decreased levels of IL10RA and TGIF1 transcripts. In addition, stimulation of THP-1 cells with budesonide statistically reduced the expression of the S100 family, IL-8, and TNF genes. In contrast, THP-1 cells treated with RG108 had increased levels of the S100 family and TNF genes. We also revealed a significant upregulation of S100A8, S100A11, and S100A12 in RA patients, especially in early RA compared to HC sera. In addition, protein levels of S100A8, S100A11, and S100A12 in RA synovial fluids compared to HC sera were significantly increased. Overall, our data suggest that the S100A8 and S100A12 proteins are strongly elevated during ongoing inflammation, so they could be used as a better biomarker of disease activity than CRP. Interestingly, epigenetic drugs can regulate these S100 proteins, suggesting their potential use in targeting RA inflammation.

Clusters of clinical and immunologic features in patients with bullous systemic lupus erythematosus: experience from a single-center cohort study in China

BackgroundBullous systemic lupus erythematosus (BSLE) is a rare subtype of systemic lupus erythematosus (SLE) that is clinically characterized by subepidermal tense vesicles or bullae. We aimed to investigate the clinical and laboratory features of patients with BSLE.MethodsWe retrospectively reviewed all patients who fulfilled the diagnostic criteria for BSLE in our institution from 2015 to 2021. Cutaneous lesions, systemic manifestations, treatment options, and outcomes were evaluated. For each case of BSLE, four controls were randomly selected from patients with single SLE. Major clinical and laboratory characteristics were compared between the two groups.ResultsAmong 4221 patients with SLE, 12 developed BSLE. Vesiculobullous lesions were the first sign in five of the BSLE patients (5/12, 41.7%) and appeared after SLE diagnosis in the remaining seven patients (7/12, 58.3%), with a median duration from SLE onset of 36 months (4–115 months). The most common BSLE-affected sites were the head and neck (10/12, 83.3%), extremities (9/12, 75.0%), trunk (7/12, 58.3%), and mucosae (6/12, 50.0%). All patients with BSLE had extra-cutaneous involvement. The SLE disease activity index score exceeded 5 in 10/12 (83.3%) patients, which indicated high disease activity. Patients in the BSLE group had significantly higher incidences of proteinuria (83.3% vs. 47.9%, P = 0.027), hematuria (75% vs. 31.3%, P = 0.006), hemolytic anemia (33.3% vs. 0%, P = 0.000), and leukopenia (66.7% vs. 25.0%, P = 0.006) than those in the control group. The use of systemic corticosteroids, immunosuppressants, dapsone, and skin care was effective in controlling disease.ConclusionsVesiculobullous lesions may be the first manifestation and indicate a high disease activity in patients with BSLE. Early diagnosis using clinical, histopathological, and immunological evaluations can lead to appropriate treatment of this progressive disease and improve prognosis.

P195 Defining the relationship between pain intensity and disease activity in patients with rheumatoid arthritis: a secondary analysis of six studies

Abstract Background/Aims Pain is the main concern of patients with rheumatoid arthritis (RA). Whilst rheumatologists often focus on reducing disease activity to improve pain the relationship between disease activity and pain in RA is incompletely characterised. Our aim was to better understand this, by defining the associations, discordance, and temporal relationships between pain intensity and disease activity in RA. Methods We undertook a secondary analysis of 1,132 patients with RA followed-up over 12 months in five trials and one observational study. Pain intensity was measured using a 100mm visual analogue scale (VAS), and disease activity using the DAS28-ESR. Relationships between 12-month pain VAS and DAS28-ESR (overall score and its components) were evaluated using Spearman correlations, linear regression models, Bland-Altman plots, and Kappa statistics. Temporal relationships were evaluated by describing mean pain intensity scores in patients over time stratified by disease activity status. Results: Associations: Linear regression models showed significant associations between pain intensity VAS and DAS28-ESR (Table). Patient global assessment (PtGA) scores explained 79.3% of the variance in pain VAS, and ESR only 19.7%. Correlations between pain intensity VAS and DAS28-ESR components were highest with PtGA (R = 0.88) and least with ESR (R = 0.10). Discordance: “fair” agreement was seen between categories of pain intensity scores (categorised as low=VAS ≤34, moderate=VAS 35-74, high=VAS >74 based on previous studies) and DAS28-ESR categories (Kappa statistic 0.287). 14% of patients in remission/low disease activity (LDA) had moderate/high pain scores; 18% of patients in high disease activity (HDA) had low pain scores. Bland-Altman plots showed many patients scored pain VAS and PtGA similarly. Temporal relationships: changes in disease activity and pain intensity scores over time mirrored each other. When patients with baseline active RA achieved 12-month remission/LDA mean pain VAS scores fell by > 60% from baseline. When patients in baseline remission/LDA had active RA at 12-months mean pain VAS scores increased by > 60% from baseline. Conclusion Whilst pain intensity is closely related to DAS28-ESR, discordance occurs in a substantial minority of patients. The relationship between DAS28-ESR and pain intensity VAS scores is largely attributable to its significant association and strong correlation with PtGA scores. Disclosure F. Ibrahim: None. M. Ma: None. D.L. Scott: None. I. Scott: None.

The Role of Shared Epitope in Rheumatoid Arthritis Prognosis in Relation to Anti-Citrullinated Protein Antibody Positivity.

IntroductionShared epitope (SE) is present in high proportions of anti-citrullinated protein antibody (ACPA) + patients with rheumatoid arthritis (RA) and is associated with poor prognosis. We assessed the role of SE in RA prognosis, in relation to ACPA positivity.MethodsPatients enrolled in the Brigham and Women’s RA Sequential Study were included. Changes from baseline in disease activity (Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI]) to 1 year were assessed. Baseline characteristics were compared by SE and ACPA status (±; chi-squared, Kruskal-Wallis). Association between number of SE alleles and ACPA status (logistic regression models), relationships between baseline characteristics and changes in disease activity (adjusted linear regression model), and effect of ACPA on the association between SE and changes in disease activity (mediation analysis) were studied.ResultsNine hundred twenty-six patients were included. SE + versus SE − patients had significantly longer disease duration and higher disease activity scores and were more likely to have erosive disease, have higher comorbidity burden, and be RF + (all p < 0.05). Among patients with one or two SE alleles (vs. 0), odds of being ACPA + were 1.97 (p = 0.0003) and 3.82 (p < 0.0001), respectively. SE + versus SE − patients had worse disease activity scores as indicated by mean increases in DAS28 (CRP) of 0.22, CDAI of 2.07, and SDAI of 2.43 over 1 year (all p < 0.05). Direct effect of SE + accounted for 76.4–80.1% of total effect in disease activity increases.ConclusionsSE is strongly associated with ACPA positivity and higher disease activity in patients with RA. SE was associated with greater increases in disease activity over 1 year, which was partially mediated by the presence of ACPA.Trial RegistrationClinicalTrials.gov identifier: NCT01793103; registration date: February 15, 2013, retrospectively registered.

The association between comorbidities and disease activity in patients with rheumatoid arthritis: a multicenter, cross-sectional cohort study in Japan with the highest proportion of elderly individuals

BackgroundThis study aimed to assess the association of disease activity with the presence of comorbidities in patients with rheumatoid arthritis, using the Akita Orthopedic Group on Rheumatoid Arthritis (AORA) registry, a multicenter, cross-sectional registry in Japan with the highest proportion of elderly people. We included 1838 patients (mean age: 66.4 years old) who visited our affiliated institutions between April 2018 and March 2019. The patients were divided into two groups based on the disease activity in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) into the remission or low disease activity group (L group) and the moderate or high disease activity group (H group). Patient demographics and comorbidities in the two groups were compared.ResultsThe most common comorbidity was hypertension (33.7%), followed by renal disease (25.2%), respiratory disease (12.2%), diabetes mellitus (8.1%), cardiovascular disease (8.0%), malignancies (5.7%), and cerebrovascular disease (4.7%). The H group was older (p<0.0001); had a higher prevalence of hypertension (p<0.0001), diabetes (p=0.0011), respiratory disease (p<0.0001), cerebrovascular disease (p<0.0001), and cardiovascular disease (p=0.0030); and was less likely to use anti-rheumatic drugs. The prevalence of comorbidities other than renal disease and malignant tumor was higher in the H group. Multivariate logistic regression analysis showed that female sex (p=0.0054), advanced Steinbrocker class (p<0.0001), high anti-citrullinated protein antibody levels (p=0.0211), high prednisolone dose (p<0.0001), and absence of biologics’ or JAK inhibitors’ use (p<0.0001) were risk factors for high disease activity, and shorter treatment period was a low-risk factor for high disease activity (p=0.0041). Among comorbidities, the presence of cerebrovascular disease (p=0.0334) was the only independent risk factor for high disease activity.ConclusionsIn our registry study with a high proportion of elderly RA patients, cerebrovascular disease was associated with high disease activity in patients with RA. Therefore, when treating elderly patients with RA, we need to pay careful attention to cerebrovascular disease, and treatment should be aimed at achieving adequate control of RA.

Short communication: Differences in clinical outcomes according to the healthcare regime in Colombian patients with rheumatoid arthritis

Introduction/ObjectivesRheumatoid arthritis (RA) is a burdensome disease from both individual and societal perspectives, in which access to a rheumatologist plays a pivotal role in disease activity and reduction of its impact. We describe preliminary results of our study aimed at exploring whether healthcare regime affiliation influences disease outcomes of Colombian patients with RA. Materials and methodsWe performed a retrospective observational study of RA patients (2010 ACR/EULAR classification criteria) with at least 3 assessments in rheumatology clinics from different healthcare regimes: Contributory (CR), Subsidized (SR), a centre of clinical excellence (C3) that follows CR patients. We retrieved data from clinical charts including a follow-up period of 2 years. ResultsWe included one hundred and sixty patients (C3: 79 [49.4%], CR: 26 [16.2%], SR: 55 [34.2%]). Median initial age was 54 years (IQR 48–62) and most patients were women (77.8%). Of the patients, 79% had established RA and 70% had high disease activity at the beginning of the follow-up. We observed statistical differences between groups with regards to (1) median time to scheduled visits, (2) percentage of visits accomplished in scheduled time, (3) median time to real visit, (4) adherence, (5) median percentage of time in high disease activity, and (6) percentage of patients in high disease activity at the end of follow-up. The best outcomes were observed in the C3 cohort. ConclusionsAccess opportunity and clinical outcomes of Colombian patients with RA appear to differ between healthcare regimes. Although systematic bias may be present due to sample size, these data imply the healthcare regime is a major determinant of disease outcomes.

Clinical utility of quantitative analysis of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis

BackgroundThe purpose of this study was to investigate the efficiency of quantitative parameters of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.MethodsWe retrospectively enrolled 65 patients with rheumatoid arthritis who underwent bone scintigraphy for diagnostic work-up. Quantitative analysis of bone scintigraphy images was conducted using an in-house software, and joint uptake ratio of 28 joints was measured for the calculation of the disease activity score of 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between joint uptake ratio and clinical findings and the efficiency of joint uptake ratio in detecting clinically active joint and high disease activity were assessed.ResultsClinically active joint (tender and/or swollen joints) showed significantly higher joint uptake ratio than did other non-affected joints (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of joint uptake ratio for identifying clinically active joint were 78.7%, 52.0%, 32.9%, and 89.1%, respectively, and those of the summed joint uptake ratio for detecting high disease activity were 92.9%, 66.8%, 43.3%, and 97.1%, respectively; the joint uptake ratio showed high detection ability, especially for active joints of the elbow, wrist, and metacarpo-phalangeal joint areas. The summed joint uptake ratio of 28 joints showed a significantly strong positive correlation with DAS28-ESR (p < 0.001; correlation coefficient, 0.725).ConclusionQuantitative parameters of bone scintigraphy showed high sensitivity and NPV for detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.

Predictive Ability of Serum IL-27 Level for Assessing Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Serum interleukin- (IL-) 27 level has been reported to increase in patients with several autoimmune diseases; however, its significance in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is unknown. In this study, we investigated the associations between serum IL-27, laboratory features, and activity of AAV and evaluate the predictive ability of serum IL-27 level for disease activity. This study included 77 AAV patients, and we collected clinical and laboratory data at blood sampling. Inflammation-related variables included white blood cell, neutrophil, lymphocyte and platelet counts, serum albumin, erythrocyte sedimentation rate, and C-reactive protein levels. Serum IL-27 and IL-18 levels were measured from stored sera using Human Magnetic Luminex® assay. High disease activity of AAV was defined as the highest tertile of Birmingham vasculitis activity score (BVAS) (≥11). The mean age of the enrolled patients was 59.9 years, and 38 (49.4%) were diagnosed as microscopic polyangiitis. In the multivariable analysis, serum albumin (β = −0.419) and serum IL-27 level (β = 0.221) were significantly associated with BVAS. Furthermore, patients with renal manifestation exhibited higher serum IL-27 (mean 308.7 pg/mL vs. 105.8 pg/mL) and IL-18 levels (mean 376.7 pg/mL vs. 270.4 pg/mL) than those without. On applying the optimal cut-off of serum IL-27 level for predicting high activity, AAV patients with serum IL − 27 level ≥ 300.8 pg/mL had a significantly higher risk for having high disease activity than those with serum IL − 27 level < 300.8 pg/mL (relative risk 3.380, 95% confidence interval 1.223, 9.345, P = 0.016). These results suggest that serum IL-27 level is associated with the cross-sectional activity and the presence of renal manifestation and could be used to predict high disease activity in patients with AAV.

Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

BackgroundObesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA.ResultsThe serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI.ConclusionsQuantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

ASAS Health Index performance in real-life Spondyloarthritis patients

Introduction: the “Assessment of Spondyloarthritis International Society Health Index” (ASASHI) questionnaire was developed to globally measure function and health status in patients with spondyloarthritis (SpA). Cut-off points have been proposed to determine different health states that were poorly evaluated in real-life patients. Objectives: to describe the health status measured by ASAS-HI in Argentine patients with axial SpA (AxSpA) and peripheral SpA (SpAp) in daily practice and to evaluate the factors associated with poor health. Materials and methods: cross-sectional, analytical and multicenter study. Patients with SpAax and SpAp were consecutively included according to ASAS criteria, from 15 Argentine centers. Statistical analysis: descriptive statistics, bivariate and multivariate analysis (multiple logistic regression) were performed to evaluate the factors associated with poor health status (ASAS-HI≥12). To analyze the construct validity of the tool, Spearman correlation was performed between the ASAS-HI and other disease evaluation parameters. Results: 274 patients with SpA were included, with a mean age of 49 (± 14) years and a median duration of the disease of 62 months (p25-75: 24-135), 155 (56.6%) were male, 129 patients (47%) with AxSpA and 145 (52.9%) SpAp. According to the ASAS-HI, 119 patients (43.4%) had good health, 117 (42.7%) had moderate health and 38 (13.9%) had poor health. In patients with SpAp, the mean ASAS-HI value was 7 (p25-75: 3-10). The ASAS-HI positively correlated with: DAS28: rho: 0.5 (p &lt;0.001) and HAQ: rho: 0.54 (p &lt;0.001). The variable independently associated with poor health status was DAS28 (OR: 1.9, 95% CI 1.1-3.4, p: 0.029). In patients with AxSpA, the mean ASAS-HI value was 6 (p25-75: 2.75-10). The ASAS-HI showed correlation with: BASDAI: rho: 0.7 (p &lt;0.001), ASDAS-ERS: rho: 0.7 (p &lt;0.001), ASQoL: rho: 0.8 (p&lt;0.001), BASFI rho: 0.75 (p &lt;0.001) 0.001). The variable that was independently associated with poor health was the ASDAS-ERS (OR 6.6, 95% CI 2-22, p 0.002). Conclusion: poor health status was independently associated with higher disease activity in patients with AxSpA and SpAp. The ASAS-HI correlated with other parameters of the disease, which reinforces the construct validity of this new tool.

TIPE2 and PCNP expression abnormalities in peripheral blood mononuclear cells associated with disease activity in rheumatoid arthritis: a meta-analysis.

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease posing a considerable burden on both individuals and society. Tumor necrosis induced protein 8-like 2 (TIPE2), closely related to PEST-containing nuclear protein (PCNP) expression, is an immune-related protein potentially involved in the pathogenesis of autoimmune diseases. In this study, we aimed to assess differential expressions of TIPE2 and PCNP in peripheral blood mononuclear cells (PBMCs) between active and inactive RA patients. Relevant studies were selected from Medline, Google Scholar, Web of Science, and China National Knowledge Infrastructure (CNKI). Only observational studies (irrespective of publication status, language, or blinding), which compared patients in high disease activity, irrespective of the sample size, with patients in low disease activity of RA were evaluated. Four studies were included with 248 patients, 138 in the active group and 110 in the inactive group. Three studies provided data on TIPE2 expression levels, where 106 patients were divided into the active group and 88 patients were divided into the inactive group. The pooled analysis revealed a statistically significant difference between the two groups (WMD: 5.60; 95% CI: 5.02-6.18). Two studies provided data on PCNP expression levels, where 64 patients were divided into the active group and 44 patients were divided into the inactive group. The pooled analysis revealed a statistically significant difference between the two groups (WMD: 7.76; 95% CI: 3.09-12.43). The expression levels of TIPE2 and PCNP are significantly increased in PBMCs of active RA patients.

Efficacy of cladribine tablets in high disease activity patients with relapsing multiple sclerosis: post hoc analysis of subgroups with and without prior disease-modifying drug treatment

Background Relapsing–remitting multiple sclerosis (RRMS) patients with high disease activity (HDA) experience more severe disease than those without HDA. This analysis describes the efficacy of cladribine tablets 3.5 mg/kg in HDA patient subgroups that were either treated with disease-modifying drugs (DMDs) prior to study entry or were treatment naïve. Methods Post hoc analysis of the 96 week Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study compared cladribine tablets 3.5 mg/kg to placebo in subgroups of patients meeting the high relapse activity plus disease activity on treatment definition of HDA. Patients were categorized into either prior DMD treatment or DMD treatment-naïve subgroups. Endpoints included annualized relapse rate (ARR), time to first relapse, time to disability progression and magnetic resonance imaging (MRI) outcomes. No inferential statistical analyses were conducted between subgroups. Results The DMD-naïve cohort (n = 187) was larger than the prior-DMD cohort (n = 102). In both the DMD-naïve and prior-DMD cohorts, cladribine tablets were associated with a reduction in ARR (rate ratio [RR]: 0.26; 95% confidence interval [CI]: 0.16–0.42; p < .0001 and RR: 0.55; 95% CI: 0.32–0.95; p = .0324, respectively). In both subgroups, cladribine tablets increased the time to relapse versus placebo (hazard ratio [HR]: 0.36; 95% CI: 0.21–0.62; p = .0002 for DMD-naïve cohort and HR: 0.50; 95% CI: 0.24–1.02; p = .0557 for prior-DMD cohort). Significant differences were observed for all assessed disability and MRI outcomes independently of previous treatment. Conclusion Post hoc evidence suggests consistent treatment benefits of cladribine tablets 3.5 mg/kg during the 96 week CLARITY study among HDA-RRMS patients who were either previously treated with DMDs or were treatment naïve.

Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis

BackgroundCirculating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).MethodsRA patients (n = 196) and healthy blood donors (n = 101), included in the cross-sectional study “Secretory ACPA in Rheumatoid Arthritis” (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE).ResultsIgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r = 0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.ConclusionSalivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.

THU0108 REAL-WORLD RADIOGRAPHIC PROGRESSION IN RA WITH BIOLOGIC DMARDS

Background:As structural damage is irreversible and strongly associated with functional disability1, it is an important outcome to be prevented in rheumatoid arthritis (RA). Acute phase markers, rheumatoid factor (RF) and anti-citrullinated protein (anti-CCP) positivity are important predictors of erosive disease2. Previous studies conducted in real life setting have divergent results regarding the role of disease activity in radiographic progression3,4.Objectives:To evaluate the impact of disease activity and biologic disease modifying anti-rheumatic drugs (bDMARDs) on radiographic progression of established RA in clinical practice in southern Brazilian public health system.Methods:Longitudinal retrospective study including patients with RA (1987 ACR criteria) treated with bDMARDs and followed from 2015 to 2019. Clinical and demographic data were collected at baseline. Radiographs of hands and feet were performed yearly. X-rays were scored according to the van der Heijde-modified total Sharp method (vdH-mTSS) in known chronological order. Clinical relevant radiographic progression (CRRP) was defined as an increase ≥3 units on the score per year5.Demographic, clinical, and radiographic characteristics of RA patients with or without relevant progression were compared with Fisher exact and Mann-Whitney test.Results:Seventy-five patients were included. The patients’ characteristics are shown in table 1. Twenty three (30%) patients presented CRRP at any time point of the follow up (figure 1). Mean DAS28-ESR at baseline was higher in patients who progressed radiographically, than those who did not progress (4.8±1.1 vs 3.5±1.1; p &lt; 0.001). No patient in remission at baseline presented with CRRP. Radiographic progression occurred in 15% of patients in low disease activity, 34% of patients in moderate disease activity and 57% of patients in high disease activity at baseline, depicting a linear relation between categories of disease activity and CRRP. RF, anti-CCP, disease duration, educational level, smoking status, total vdH-mTSS at baseline, number and duration of biologic DMARDs were not associated with CRRP. No single biologic DMARD was associated with worse radiological prognosis.Table 1.Baseline characteristics and bDMARD treatment during 5 years of follow upCharacteristicsN = 75Age, yrs, mean ± SD58.1 ± 10.1Female, n (%)65 (86.6)Disease duration, yrs, mean ± SD16.2 ± 7.6IgM RF positivity, n (%)69 (92)Anti-CCP positivity, n (%)27 (75) *DAS28-ESR, mean ± SD4.2 ± 1.0Educational level, n(%) Elementary school (≤ 8years)49 (65) Intermediate school (9-12 years)23 (30,6) University/college degree3 (4)SmokingCurrent or former31 (41.3)Never44 (58,7)vdH-mTSS, median (IQR)21 (5-53)Number of bDMARD, mean ± SD2.4 ± 1.1Duration of bDMARD, yrs, mean ± SD7.4 ± 2.6Methotrexate use, n, %61 (81)Biologic DMARD184**TNF inhibitors, n, %106 (57.6)Tocilizumab, n, %30 (16.3)Abatacept, n, %25 (13.6)Rituximab, n, %23 (12.5)RF rheumatoid fator anti-CCP anti-citrullinated protein bDMARD biologic disease-modifying anti-rheumatic drug ESR erythrocyte sedimentation rate DAS28 disease activity in 28 joints vdH-mTSS van der Heijde-modified total Sharp score IQR interquartile range *information available from 36 patients **all bDMARD treatmentsConclusion:In contrast to controlled clinical trials, real-world studies have shown that patients with RA treated with bDMARD still develop radiological progression. We observed that despite prognostic factors, achievement of treatment target is the most important factor to prevent articular damage in RA.

Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab

BackgroundRheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant,...

Cost Effectiveness of Cladribine Tablets for the Treatment of Relapsing-Remitting Multiple Sclerosis in The Netherlands.

BackgroundCladribine tablets have recently become available in The Netherlands for patients with relapsing–remitting multiple sclerosis (RRMS) as a disease-modifying agent that reduces the frequency and severity of relapses and delays disability progression.ObjectiveThe aim of this study was to evaluate the cost effectiveness of cladribine tablets, compared with alternative options, in the treatment of RRMS patients with high disease activity (HDA) and patients with rapidly evolving severe (RES) MS in The Netherlands.MethodsA Markov model was developed simulating the costs and effects of RRMS treatment. For HDA, alemtuzumab and fingolimod were used as comparators; natalizumab was used for the RES subpopulation. The analysis included a societal perspective and a value-of-information (VOI) analysis.ResultsFor the HDA subpopulation, treatment with cladribine tablets was the cost-effective (dominant) strategy compared with alemtuzumab and fingolimod, with 50.9% and 98.2%, respectively, probability of being cost effective at a threshold of €50,000/QALY gained and a net monetary benefit (NMB) of €10,866 and €151,115, respectively. For the RES subpopulation, treatment with cladribine tablets dominated treatment with natalizumab, with 94.1% probability of being cost effective at a threshold of €50,000/QALY gained and an NMB of €122,986. Note that these outcomes are driven by the lower costs of cladribine tablets. Efficacy differences were small, very uncertain, and likely not clinically meaningful. The probabilistic sensitivity analyses showed significant overlap in the credible intervals for total lifetime QALY outcomes and costs of cladribine tablets and all relevant comparators. The population-level VOI amounted to €19,295,441.ConclusionsThe base-case analysis shows that treatment of RRMS with cladribine tablets is cost effective versus alemtuzumab and fingolimod in HDA patients, and cost effective versus natalizumab in RES patients, at a threshold of €50,000. Driven by the lower costs, cladribine tablets were cost effective (dominant) in all base-case analyses. However, given that outcomes are based on indirect comparisons and post hoc subgroup analysis, as well as the uncertainty surrounding the outcomes, the results presented in this paper should be interpreted with caution.Electronic supplementary materialThe online version of this article (10.1007/s40258-019-00500-8) contains supplementary material, which is available to authorized users.

Does vitamin D deficiency contribute to higher disease activity in patients with spondyloarthritis?

Introduction: This study aimed to compare serum vitamin D levels in Spondyloarthritis (SpA) patients and control group and to evaluate the associations between vitamin D and disease activity in SpA patients. Methodology: In this study, 86 SpA patients according to the International Criteria and 117 age and sex-matched healthy controls were included. In patients, clinical examination was performed and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were recorded. Serum 25(OH)D3 concentration was measured using ELISA kit. Results: Serum 25(OH)D3 levels in SpA patients were significantly lower than healthy controls (p < 0.001). Vitamin D deficiency and insufficiency frequency in the SpA group was significantly more than control group (p < 0.001). No significant difference was observed in the activity of SpA in different serum levels of 25(OH)D. Also, no significant correlations were observed between serum 25(OH)D3 with clinical findings as well as with BASDAI and BASFI (P > 0.05). Discussion and conclusion: Although our study revealed lower serum 25(OH)D3 levels in SpA patients compared to healthy controls, there were not any significant correlations between its serum levels with severity of disease. However, correction of vitamin D status may be beneficial in controlling inflammation and disease activity.