Association of Baseline Serum Soluble Tumour Necrosis Factor Receptor Levels with the Response of Rheumatoid Arthritis to Janus Kinase Inhibitor Therapy.

BackgroundExosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA).MethodsThe study population consisted of 60 patients with RA: 30 in the clinical remission (CR) group with a Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) ≤2.6 and 30 in the non-clinical remission (non-CR) group with a DAS28-ESR >2.6. Preparation of exosomes from patient serum samples was performed with the ExoQuick kit, and protein identification/quantification was performed using tandem mass tag labeling/mass spectrometry and an enzyme-linked immunosorbent assay. Comparisons between groups were made using Student’s t test or the Mann-Whitney U test, as appropriate. Spearman’s correlation coefficients (ρ) were calculated.ResultsWe identified six candidate proteins. Exosomal levels of amyloid A (AA) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) differed between the CR and non-CR groups. Both serum and exosomal AA levels were higher in the non-CR group than in the CR group (p = 0.001). Significant positive correlations were found between exosomal AA and C-reactive protein (CRP) as well as between serum AA and CRP (ρ = 0.614, p = 0.001, and ρ = 0.624, p = 0.001, respectively). Although serum levels of LYVE-1 did not differ between the non-CR and CR groups, exosomal levels of LYVE-1 were lower in the non-CR group than in the CR group (p = 0.01). We identified positive correlations between serum/exosomal LYVE-1 and CRP only in the non-CR group (serum ρ = 0.376, p = 0.04; exosome ρ = 0.545, p = 0.002).ConclusionsExosomal LYVE-1 shows potential for use as an additional marker of disease activity in patients with RA, and exosomes may carry other useful markers for RA.

BackgroundExosomes, membrane-bound vesicles of 40–100 nm in diameter, have protein and lipid composition that depends on the cell origin, the state of activation, infection and/or transformation of the parent cells....

This study aimed to evaluate whether targeting clinical remission is appropriate for suppressing physical dysfunction in patients with early rheumatoid arthritis (RA). Subjects were all 75 early RA patients (within 2years of onset) who were continuously treated with biologics for 12months at our hospital. We evaluated the Simplified Disease Activity Index (SDAI) and Disability Index of the Health Assessment Questionnaire (HAQ-DI) at 3, 6, and 12months from the initiation of biologics therapy. Rates of functional remission (HAQ-DI≤0.5) at 12months in the clinical remission (SDAI≤3.3) group and the low disease activity [LDA (3.3<SDAI≤11)] group were 97 and 86%, respectively. Multivariate logistic regression analysis revealed that duration of disease and SDAI at 6months were significantly associated with the achievement of functional remission at 12months. The best cut-off value of SDAI at 6months for predicting functional remission at 12months was 15.7 by receiver operating characteristic curve analysis. HAQ-DI scores in the LDA group were significantly higher than those in the clinical remission group at 6 and 12months. The mean HAQ-DI score at 12months in the clinical remission group improved significantly relative to the mean HAQ-DI score at 6months in the LDA group. Our findings highlight the importance of achieving LDA at least by 6months after initiating biologics therapy, and achieving clinical remission as soon as possible, in order to minimize physical dysfunction in patients with early RA.

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease that is characterised by severe tissue damage and chronic synovial inflammation.1 Using analysis of gene polymorphism, biochemical assays, and proteomics approaches, several...

THU0109 Treating to target ultrasound with clinical remission better effects than clinical remission in RRP

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the multiple joints.The elucidation of the pathogenesis of RA has progressed dramatically in recent decades, and among the many...

Clinical remission at two years post-diagnosis of asthma and its association with clinical outcomes: A retrospective cohort study in asthma patients with maintenance inhaler therapy.

Background:Janus kinase (JAK) inhibitors block the signaling of multiple JAK-dependent cytokines. A number of studies have reported on the clinical efficacy of JAK inhibitors in patients with rheumatoid arthritis (RA)....

Relevance. A variety of targeted therapies for rheumatoid arthritis (RA) treatment exist. Therefore, reliable predictors are needed that could be used to accurately predict the efficacy or inefficacy of these therapies in individual patients. This could allow clinicians to improve diagnosis and prognosis, to make the treatment personalized and to reduce healthcare expenses. Objectives: to analyze and systemize the predictors of response to treatment in patients with RA. Materials and Methods. We analyzed the recently discovered predictors of treatment response in RA patients using papers cited on PubMed, Lilacs, and EMBASE databases from Jan 2005 until Jan 2020. Predictive factors were grouped into four categories: methotrexate (MTX)-treated RA, tumor necrosis factor (TNF)-α inhibitors-treated RA, interleukin (IL)-6 inhibitors-treated RA, and rituximab (RTX)-treated RA. Results. Based on the results of several studies, predictors of response to methotrexate were high Disease Activity Score (DAS), concentration of myeloid-related proteins 8/14, high P-glycoprotein levels, low serum calprotectin and leptin levels, baseline serum concentration of tumor necrosis factor (TNF)-α, TNF receptor I, interleukin (IL)-1β, soluble CD163, numbers of CD14+highCD16, vascular cell adhesion molecule, lower expression of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p. A positive response to biological therapy was determined by male gender, younger age, lower health assessment questionnaire, erythrocyte sedimentation rate or C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, tender joint count (or swollen joint count) scores, absence of comorbidities, baseline albumin, IL-34, IL-1β, D-dimer, fibrinogen, matrix metalloproteinase 3, DAS 28 and Simplified Disease Activity Index (SDAI). The plasma interferon (IFN) activity and the IFN beta/alpha ratio, IL-1Ra level were predictive in TNF antagonist-treated patients. Predictors of response to IL-6 inhibitors were anti–citrullinated protein antibody (ACPA)+, baseline Sharp/van der Heijde score, myeloid soluble intercellular adhesion molecule 1, serum levels of sIL-6R, IL-8, calprotectin, and lymphoid activation and bone remodeling markers. The prediction of the best response for rituximab was determined to be a combination of IL-33, rheumatoid factor or ACPA, IgG, and also lower number of previous biological therapies. Genetic factors, such as single-nucleotide polymorphisms at gene locus rs10919563, rs11541076, rs12083537, rs11265618, and rs1801274, and rs396991 can also be used to predict a response to treatment. Conclusions. One of the leading problems in the development of predictors remains the collection of high-quality and complete information from a large number of patients. For this, it is necessary to develop an digital program for collecting specific data (depending on the specific disease) and developing new algorithms for predicting the response to treatment.

FRI0056 Serum IL-10 and IP-10 Levels is an Important Predictor of Response to Tocilizumab in Bio-Naïve RA Patients

OP0283 Ultrasonographic evaluation in rheumatoid arthritis using the global omeract/eular ultrasound synovitis score (GLOESS)

Background:Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2 = 3.937, P = 0.047), SDAI (χ2 = 4.666, P = 0.031), and CliDR criteria (χ2 = 4.297, P = 0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z = −2.295, P = 0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

SAT0157 Discontinuation of etanercept in rheumatoid arthritis patients in clinical remission: Two-year outcome

Objectives: To assess the role of musculoskeletal ultrasound (MSUS) in selecting patients with rheumatoid arthritis (RA) in sustained clinical remission, suitable for tapering of biologic therapy (BT), and monitoring for a subclinical relapse. Methods: In this prospective study, seventy-eight patients with RA in sustained Disease Activity for twenty-eight joints (DAS28) clinical remission underwent ultrasound (US) examination of twenty-two joints (bilaterally wrists and metacarpophalangeal and proximal interphalangeal joints). US assessment was performed on gray scale ultrasound (GSUS) and power Doppler US (PDUS) to select patients in imaging remission, defined as a total PD score of synovitis = 0. Group 1 consisted of patients in clinical and imaging remission, in which tapering of BT was done through spacing of the Tumour Necrosis Factor Alpha (TNF-α) blocker. Group 2 consisted of patients only in clinical remission (PDUS > 0), who continued standard therapy. Clinical and US assessment was done at months 6 and 12, and the rate of a clinical (defined as DAS28 ≥ 2.6) and an US relapse (PDUS score ≥ 1) was recorded. Results: Thirty-eight patients were in clinical and US remission (group 1) and forty patients only in clinical remission (group 2). At month 6, 26% of patients in group 1 and 10% in group 2 experienced a clinical and an US relapse, whereas 20% and 15% of them, respectively, only an US relapse. At month 12, 26% of patients in group 1 and 20% of patients in group 2 experienced a clinical and an US relapse, whereas 35% and 22% of them, respectively, only an US relapse. Conclusions: Real-world data show that MSUS is a useful tool to identify RA patients in sustained clinical remission appropriate for BT tapering. US monitoring could predict a clinical relapse and the need to re-escalate treatment in patients with subclinical US relapse during BT tapering.

Objectives: To explore the influencing factors of the efficacy of vedolizumab (VDZ) in the treatment of ulcerative colitis (UC) patients. Methods: The clinical data of patients with active UC, who underwent VDZ treatment from November 2020 to February 2024 in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively collected. Each patient received intravenous injection of VDZ (300 mg per dose) at weeks 0, 2 and 6, and then received the same dose of intravenous injection of VDZ every 8 weeks. At week 16, the patients were divided into clinical remission group (who achieved clinical remission) and clinical non-remission group. At week 34, the patients were divided into mucosal healing group (who achieved mucosal healing) and mucosal non-healing group, as well as pathological remission group (who achieved pathological remission) and pathological non-remission group. The serum cytokines levels [interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α] were detected at week 0, and 16, and the magnitude of cytokine changes (the difference between week 16 and week 0) was caculated. At week 16, the clinical remission of the patients was evaluated. At week 34, the patients underwent re-examination of colonoscopy to assess intestinal inflammation and histopathological activity. Multivariate logistic regression models were used to explore the influencing factors of clinical remission, mucosal healing, and pathological remission. Results: A total of 100 patients were included, 54 males and 46 females, aged (43.5±13.7) years. At week 16, there were 68 patients in clinical remission group and 32 patients in clinical non-remission group. In clinical remission group, the reductions of IL-6 [M (Q1, Q3), -0.85 (-1.23, -0.46) vs -0.26 (-1.04, 0.19) ng/L, P<0.001] and IL-6+TNF-α [-0.99 (-1.46, -0.52) vs -0.30 (-0.83, 0.47) ng/L,P<0.001] were higher than those in clinical non-remission group. IL-6 reduction≥0.40 ng/L (OR=15.33, 95%CI: 4.42-53.19), disease location limited to the rectum and left sided colon (OR=0.16, 95%CI: 0.05-0.51) and baseline partial Mayo score<5 scores (OR=0.25, 95%CI: 0.07-0.84) were favorable factors of clinical remission at week 16. At week 34, a total of 87 patients underwent re-examination of colonoscopy. There were 43 patients in mucosal healing group and 44 patients in mucosal non-healing group. In mucosal healing group, the reductions of IL-6 and IL-6+TNF-α were higher than those in mucosal non-healing group, and the increase in IL-10 was also higher than that in the mucosal non healing group (all P<0.05). IL-6 reduction≥0.45 ng/L (OR=13.53, 95%CI:2.67-68.45) and baseline Mayo endoscopic score (MES)<2 scores (OR=0.08, 95%CI: 0.01-0.65) were the favorable factors of mucosal healing at week 34. At week 34, there were 23 patients in pathological remission group and 64 patients in pathological non-remission group. The reductions of IL-6 and IL-6+TNF-α, as well as the increase of IL-10 were higher than those in pathological non-remission group (all P<0.05). IL-6 reduction≥0.45 ng/L (OR=18.23, 95%CI: 2.32-143.52) was a favorable factor of pathological remission at week 34. Conclusions: IL-6 reduction≥0.40 ng/L, disease location limited to the rectum and left sided colon, as well as baseline partial Mayo score<5 scores are favorable factors of clinical remission at week 16. IL-6 reduction≥0.45 ng/L and baseline MES<2 scores are favorable factors of mucosal healing at week 34. IL-6 reduction≥0.45 ng/L is a favorable factor of pathological remission at week 34.