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ID PMID Title PublicationDate abstract
34485325 Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry an 2021 Background: Haemophilus parasuis (Hps; now Glaesserella parasuis) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261-273 of collagen type 2 (Coll(261-273)), a possible autoantigen in rheumatoid arthritis (RA). Objectives/methods: We tested the presence of Hps sequencing 16S ribosomal RNA in crevicular fluid, synovial fluids, and tissues in patients with arthritis (RA and other peripheral arthritides) and in healthy controls. Moreover, we examined the cross-recognition of Hps by Coll(261-273)-specific T cells in HLA-DRB1(*)04(pos) RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping. Results: Hps DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti-Hps IgM and IgG titers were detectable and correlated with disease duration and the age of the patients. Peripheral blood mononuclear cells (PBMCs) were stimulated with Hps virulence-associated trimeric autotransporter peptide (VtaA10(755-766)), homologous to human Coll(261-273) or co-cultured with live Hps. In both conditions, the expanded TCR repertoire overlapped with Coll(261-273) and led to the production of IL-17. Discussion: We show that the DNA of an infectious agent (Hps), not previously described as pathogen in humans, is present in most patients with RA and that an Hps peptide is able to activate T cells specific for Coll(261-273), likely inducing or maintaining a molecular mimicry mechanism. Conclusion: The cross-reactivity between VtaA10(755-766) of a non-human infectious agent and human Coll(261-273) suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope.
34407599 Prevalence, incidence, and risk factors of malignancy in patients with rheumatoid arthriti 2021 Aug 20 BACKGROUND/AIMS: This study aims to evaluate the incidence of malignancy in patients with rheumatoid arthritis (RA) and to investigate risk factors for such in a nationwide, population-based cohort. METHODS: In a large, prospective, observational cohort study, 5,077 patients with RA were enrolled from July 2009 to December 2011 and followed until February 2017. Standardized incidence ratios (SIRs) for malignancy were calculated using age- and sex-specific cancer rates in the Korean general population. Poisson regression was used to identify the risk of incident malignancy. RESULTS: The cohort included 5,023 participants with RA contributing 16,689 person-years of follow-up. A total of 148 malignancies were recorded. The risks of stomach cancer (SIR, 0.41; 95% confidence interval [CI], 0.21 to 0.74), colon cancer (SIR, 0.13; 95% CI, 0.03 to 0.37), and lung cancer (SIR, 0.35; 95% CI, 0.14 to 0.72) were lower in RA patients than in the general population. Poisson regression modeling demonstrated that the malignancy risk was more than two-fold greater in patients with thyroid disease than in those without thyroid disease. Hydroxychloroquine therapy was associated with a reduced risk (relative risk, 0.39; 95% CI, 0.189 to 0.801) of malignancy development. CONCLUSIONS: The overall risk of malignancy in patients with RA is decreased relative to in the general population. In particular, stomach, colon, and lung cancers in Korean RA patients are less common, while brain and central nervous system cancers in male RA patients are more frequent. The patients with thyroid disease and longer RA disease duration were at increased risk for developing malignancy, while hydroxychloroquine users were at lower risk.
33589099 Rheumatic Complications of Immune Checkpoint Inhibitors. 2021 Mar Immune checkpoint inhibitors activate the immune system to combat cancer. In doing so, however, they can cause immune-related adverse events (irAEs), including rheumatic syndromes, such as inflammatory arthritis, polymyalgia rheumatica, and myositis. This article reviews rheumatic irAEs that may be encountered in the general medicine practice and provides guidance to support prompt recognition, referral, and treatment of these patients.
34350373 Reduced cognitive ability in people with rheumatoid arthritis compared with age-matched he 2021 OBJECTIVE: The aim was to compare the cognitive ability of people with RA with healthy controls (HCs). METHODS: People with RA were recruited from the Norfolk Arthritis Register (NOAR), a population-based cohort study of people with inflammatory arthritis. Data on aged-matched HCs (people with no cognitive impairment) came from the comparison arm of The Dementia Research and Care Clinic Study (TRACC). People with RA and HCs performed a range of cognitive ability tasks to assess attention, memory, verbal fluency, language, visuospatial skills, emotional recognition, executive function and theory of mind. A score of <88 on the Addenbrooke's Cognitive Examination III was considered cognitive impairment. Scores were compared using linear regression adjusting for age, sex, smoking status, education, BMI, anxiety and depression. RESULTS: Thirty-eight people with RA [mean (S.D.) age: 69.1 (8.0) years; 25 (65.8%) women] were matched with 28 HCs [mean (S.D.) age: 68.2 (6.4) years; 15 (53.6%) women]. Twenty-three (60.5%) people with RA were considered to have mild cognitive impairment [mean (S.D.) Addenbrooke's Cognitive Examination III: RA = 85.2 (7.4), HC = 96.0 (2.5)]. People with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with HCs, after adjustment for confounders. CONCLUSION: People with RA had cognitive impairments in a range of domains. People with RA might benefit from cognitive impairment screening to allow for early administration of appropriate interventions.
33690996 Periodontitis in Italian patients with established rheumatoid arthritis: A cross-sectional 2021 Mar 10 OBJECTIVE: To assess the prevalence and severity of periodontitis (P) among Italian patients affected by rheumatoid arthritis (RA). MATERIALS AND METHODS: A full-mouth periodontal examination and a rheumatologic examination were performed. RA disease activity was scored using the DAS28. Serum analyses investigated levels of rheumatoid factor, anti-citrullinated protein antibodies (ACPAs), C-reactive protein, erythrocyte sedimentation rate and fibrinogen. Information concerning smoking, body mass index and RA medical therapy was collected. Data were analysed by Student's t test, chi-square test, binary logistic regression and Spearman's rank. RESULTS: This cross-sectional study included 120 subjects, 77 had both diseases while 43 only had RA. The number of teeth present was statistically lower in the RA-P compared to the RA group (p < .05). There were statistically more subjects seropositive for ACPAs in the RA-P group (62.3% vs. 32.6%, p < .05). RA-P patients had an adjusted OR = 2.9 of presenting a moderate-severe DAS28 score (DAS28 ≥ 3.2). CONCLUSIONS: Higher prevalence of severe P was noted among RA subjects. The clinical severity of RA was strongly correlated with the clinical periodontal parameters, and RA subjects also affected by P had an OR of 2.9 for presenting with a moderate-severe RA (DAS28 score ≥ 3.2).
33428103 Analysis of the clinical characteristics of arthritis with renal disease caused by a NPHS2 2021 Aug The co-existence of juvenile idiopathic arthritis (JIA)/rheumatoid arthritis (RA) and focal segmental glomerulosclerosis (FSGS) is rare, and the existence of co-pathogenesis remains unknown. In this study, we analyzed the clinical and gene mutation characteristics of a patient with JIA and FSGS caused by a NPHS2 gene mutation, and evaluated the potential connections between these two diseases. We summarized the clinical manifestations, related examination results, and gene mutation characteristics of the patient who presented at our center and six reported cases of arthritis with renal disease. Most of the cases were polyarticular arthritis with varying degrees of renal damage (hematuria, proteinuria, and renal dysfunction) and different prognoses. Among these patients, two developed end-stage renal disease (ESRD), with one dying as a result, while the other patients had a relatively good prognosis. Patients with a family history of renal disease had a poor prognosis. After excluding occasional factors and drug influences, our analysis indicated the existence of co-pathogenesis of arthritis with renal damage (especially FSGS). NPHS2 mutations might account for the family aggregation. Therefore, evaluation of more clinical cases is necessary to further clarify the underlying co-pathogenesis of these diseases.
34519964 Identification of a Rule to Predict Response to Sarilumab in Patients with Rheumatoid Arth 2021 Dec INTRODUCTION: In rheumatoid arthritis, time spent using ineffective medications may lead to irreversible disease progression. Despite availability of targeted treatments, only a minority of patients achieve sustained remission, and little evidence exists to direct the choice of biologic disease-modifying antirheumatic drugs in individual patients. Machine learning was used to identify a rule to predict the response to sarilumab and discriminate between responses to sarilumab versus adalimumab, with a focus on clinically feasible blood biomarkers. METHODS: The decision tree model GUIDE was trained using a data subset from the sarilumab trial with the most biomarker data, MOBILITY, to identify a rule to predict disease activity after sarilumab 200 mg. The training set comprised 18 categorical and 24 continuous baseline variables; some data were omitted from training and used for validation by the algorithm (cross-validation). The rule was tested using full datasets from four trials (MOBILITY, MONARCH, TARGET, and ASCERTAIN), focusing on the recommended sarilumab dose of 200 mg. RESULTS: In the training set, the presence of anti-cyclic citrullinated peptide antibodies, combined with C-reactive protein > 12.3 mg/l, was identified as the "rule" that predicts American College of Rheumatology 20% response (ACR20) to sarilumab. In testing, the rule reliably predicted response to sarilumab in MOBILITY, MONARCH, and ASCERTAIN for many efficacy parameters (e.g., ACR70 and the 28-joint disease activity score using CRP [DAS28-CRP] remission). The rule applied less to TARGET, which recruited individuals refractory to tumor necrosis factor inhibitors. The potential clinical benefit of the rule was highlighted in a clinical scenario based on MONARCH data, which found that increased ACR70 rates could be achieved by treating either rule-positive patients with sarilumab or rule-negative patients with adalimumab. CONCLUSIONS: Well-established and clinically feasible blood biomarkers can guide individual treatment choice. Real-world validation of the rule identified in this post hoc analysis is merited. CLINICAL TRIAL REGISTRATION: NCT01061736, NCT02332590, NCT01709578, NCT01768572.
33628569 Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumati 2021 Biological disease-modifying antirheumatic drugs (bDMARDs) are very effective for treating rheumatoid arthritis (RA). However, they sometimes induce adverse events such as psoriasis-like skin lesions. We describe psoriasis-like skin lesions that developed simultaneously with an RA flare in patient 1 during treatment with abatacept and in patient 2 soon after starting certolizumab pegol. The skin lesions persisted in patient 2 despite stopping certolizumab. Baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. The RA went into remission in both patients, and the psoriasis-like skin lesions disappeared within four weeks (patient 1) and three months (patient 2).
34757493 Risk factors for progression of interstitial lung disease in Sjögren's syndrome: a single 2022 Apr OBJECTIVE: To identify clinical characteristics and risk factors related to the progression of interstitial lung disease (ILD) in patients with primary Sjögren's syndrome (pSS). METHODS: In this single-centered, retrospective study, a total of 83 identified pSS-ILD patients with relatively complete clinical data were finally enrolled. Clinical symptoms, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results were collected. A logistic regression analysis was performed to determine the independent risk factors for ILD progression, and a nomogram was plotted to construct a predictive model. RESULTS: The prevalence of pSS-ILD in our study was 18.89%. Among the 83 enrolled patients, 32 (38.6%) underwent ILD progression. The characteristic features associated with the progression of ILD included male sex, non-sicca onset, reticular pattern on HRCT, higher levels of baseline lactic dehydrogenase (LDH), and low baseline forced vital capacity (FVC). The results of multivariate logistic regression indicated that LDH (OR 1.008, p = 0.030) was an independent risk factor for ILD progression, while sicca onset (OR 0.254, p = 0.044) and FVC (OR 0.952, p = 0.003) were protective factors for ILD progression. A simple predictive model for ILD progression in pSS was developed and validated. CONCLUSION: pSS patients with non-sicca onset, high baseline LDH level, and low baseline FVC were at higher risk of ILD progression.
33894442 Occult primary Sjögren Syndrome in patients with interstitial pneumonia with autoimmune f 2021 Jun INTRODUCTION/OBJECTIVES: To define the performance of Minor Salivary Gland Biopsy (MSGB) and Dry Eye Tests (DET) to detect occult Sjögren Syndrome (SS) among Interstitial Pneumonia with Autoimmune Features (IPAF) patients. METHODS: Prospective study. Interstitial Lung Disease (ILD) patients without defined Connective Tissue Disease and one or more IPAF classification domains or xerophthalmia were included. MSGB, Schirmer's test (ST) and Ocular Staining Score (OSS) were performed in a blinded manner by experienced specialists. MSGB with ≥1 focus of lymphocytes and Dry Eye Test (DET) with OSS ≥ 5 and/or ST < 5 s were considered positive. SS was diagnosed according to the ACR 2016 criteria. RESULTS: 534 patients on the first consult were screened. 67 patients had at least one IPAF criteria, 53 (79.1%) female, mean age (SD) 64.2 years old (10.8). Positive ST in 36 (53.7%), positive OSS in 29 (43.3%) and positive MSGB in 36 (53.7%) were found. Finally, 27 (40.3%) met SS diagnostic criteria. 25 (37.3%) and 18 (26.8%) of them did not report dry eyes or dry mouth, respectively. 53 (79.1%) had negative anti SSA/Ro, 57 (85.1%) had negative anti LA/SSB, 30 (44.7%) had negative ANA, and 52 (77.6%) had negative RF, respectively. A significantly higher proportion of ANA (+), anti-SSA/Ro (+), anti-SSB/La (+), positive DET and positive MSGB were found in the SS population. CONCLUSIONS: A significant proportion of patients with occult SS were found in our study. MSGB and DET may be considered in the evaluation of IPAF patients.
34091811 Quinone-rich fraction of Ardisia crispa (Thunb.) A. DC roots alters angiogenic cascade in 2021 Jun Rheumatoid arthritis (RA) is a chronic joint disorder, of which, excessive angiogenesis is the well-established factor contributing to synovitis and joint destruction. Ardisia crispa (Primulaceae) is a medicinal herb with evidenced anti-angiogenic properties, attributed to 2-methoxy-6-undecyl-1,4-benzoquinone (BQ) found in its roots. However, it is still unclear how BQ is able to inhibit angiogenesis in RA. Hence, we investigated the anti-arthritic potential of quinone-rich fraction (QRF) separated from Ardisia crispa roots hexane extract (ACRH) by targeting angiogenesis on collagen-induced arthritis (CIA) in rats. The QRF was priorly identified by quantifying the BQ content in the fraction using GC-MS. Male Sprague-Dawley rats (n = 6) were initially immunised with type II collagen (150 µg) subcutaneously at the base of the tail on day 0. QRF (3, 10, and 30 mg/kg/day) and celecoxib (5 mg/kg/day) were orally administered for 13 consecutive days starting from day 14 post-induction, except for the vehicle and arthritic controls. QRF at all dosages moderately ameliorated the arthritic scores, ankle swelling, and hind paw oedema with no significant (p > 0.05) modulation on the bodyweights and organ weights (i.e., liver, kidney, and spleen). Treatment with QRF at 3, 10, and 30 mg/kg, significantly (p < 0.05) attenuated VEGF-A, PI3K, AKT, NF-κB, p38, STAT3, and STAT5 proteins and markedly restored the increased synovial microvessel densities (MVD) to the normal level in arthritic rats in a dose-independent manner. In conclusion, QRF conferred the anti-arthritic effect via angiogenesis inhibition in vivo, credited to the BQ content and synergism, at least in part, by other phytoconstituents.
34391476 Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthr 2021 Aug 14 OBJECTIVE: During rheumatoid arthritis (RA), the angiogenic processes, occurring with pannus-formation, may be a therapeutic target. JAK/STAT-pathway may play a role and the aim of this work was to investigate the inhibiting role of a JAK-inhibitor, tofacitinib, on the angiogenic mechanisms occurring during RA. METHODS: After ethical approval, JAK-1, JAK-3, STAT-1, STAT-3 and VEGF expression was evaluated on RA-synovial-tissues. In vitro, endothelial cells (ECs), stimulated with 20 ng/ml of VEGF and/or 1 μM of tofacitinib, were assessed for tube formation, migration and proliferation, by Matrigel, Boyden chamber assay and ki67 gene-expression. In vivo, 32 mice received collagen (collagen-induced arthritis (CIA)) and 32 mice PBS (control). At day 19, CIA and controls mice were divided: 16 mice receiving vehicle and 16 mice receiving tofacitinib. At day 35, the arthritis score, the thickness of paw joints and the serum levels of VEGF and Ang-2 were evaluated. RESULTS: The expression of JAK-1, JAK-3, STAT-1, STAT-3 and VEGF in synovial tissue of RA-patients were significantly higher than healthy controls. In vitro, tofacitinib inhibited the ECs ability to form vessels, to proliferate and to migrate. In vivo, administration of tofacitinib prevented the increase of the arthritis score, the paw thickness, the synovial vessels and VEGF and Ang-2 serum-accumulation, when compared to CIA without tofacitinib. CONCLUSIONS: We explored the anti-angiogenic role of tofacitinib, reporting its ability to inhibit in vitro the angiogenic mechanisms of ECs and in vivo the formation of new synovial vessels, occurring in CIA model. These findings suggest that the therapeutic effect of tofacitinib during RA may be also related to its anti-angiogenic activity.
35052724 Restoring the Balance between Pro-Inflammatory and Anti-Inflammatory Cytokines in the Trea 2021 Dec 26 Rheumatoid arthritis (RA) and other autoimmune inflammatory diseases are examples of imbalances within the immune system (disrupted homeostasis) that arise from the effects of an accumulation of environmental and habitual insults over a lifetime, combined with genetic predispositions. This review compares current immunotherapies-(1) disease-modifying anti-rheumatic drugs (DMARDs) and (2) Janus kinase (JAK) inhibitors (jakinibs)-to a newer approach-(3) therapeutic vaccines (using the LEAPS vaccine approach). The Ligand Epitope Antigen Presentation System (LEAPS) therapies are capable of inhibiting ongoing disease progression in animal models. Whereas DMARDs ablate or inhibit specific proinflammatory cytokines or cells and jakinibs inhibit the receptor activation cascade for expression of proinflammatory cytokines, the LEAPS therapeutic vaccines specifically modulate the ongoing antigen-specific, disease-driving, proinflammatory T memory cell responses. This decreases disease presentation and changes the cytokine conversation to decrease the expression of inflammatory cytokines (IL-17, IL-1(α or β), IL-6, IFN-γ, TNF-α) while increasing the expression of regulatory cytokines (IL-4, IL-10, TGF-β). This review refocuses the purpose of therapy for RA towards rebalancing the immune system rather than compromising specific components to stop disease. This review is intended to be thought provoking and look forward towards new therapeutic modalities rather than present a final definitive report.
34477117 Characteristics and mortality in primary Sjögren syndrome-related interstitial lung disea 2021 Sep 3 Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ± 11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.
34761312 The lessebo effect in randomized controlled trials of rituximab in patients with rheumatoi 2021 Nov 10 OBJECTIVE: The goal of this study was to assess the impact of negative expectations associated with receiving a placebo (the lessebo effect) on efficacy outcomes in randomized clinical trials (RCTs) of rituximab in patients with rheumatoid arthritis (RA). METHODS: We performed a meta-analysis on the American College of Rheumatology 20%, 50%, and 70% (ACR20, 50, 70) response rates in the placebo and active (biosimilar)-controlled groups (reference-pbo and reference-bs) of rituximab showing an insufficient response to methotrexate or tumor necrosis factor. We evaluated the difference in ACR20, 50, 70 response rates between the two groups (reference-bs vs. reference-pbo). RESULTS: Nine RCTs included a total of 2734 patients with RA. The pooled incidence of ACR20 response rate in the placebo- and active-controlled groups of the rituximab RCTs for RA was 53.1% (95% confidence interval [CI] 49.9-56.3%) and 75.0% (95% CI 71.2-78.4%), respectively. The difference in the ACR20 response rate between the placebo- and active-controlled groups was -20.9% (95% CI -26.9 to 61.9%, p < 0.001). The pooled incidence of ACR50 response rate in the placebo- and active-controlled groups of the rituximab RCTs for RA was 29.0% (95% CI 26.2-32.0%) and 47.4% (95% CI 43.2-51.6%), respectively. The ACR50 response rates were significantly higher in the active-controlled groups than in the placebo-controlled groups (-18.4%; 95% CI -18.4 to -13.4%, p < 0.001). The difference in the ACR70 response rate between the placebo- and active-controlled groups was -14.9% (95% CI -22.2 to -7.6%, p < 0.001). The ACR20, 50, 70 response rates were significantly higher in the active-controlled groups than in the placebo-controlled group. CONCLUSION: This study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the ACR20, 50, 70 response rates in rituximab RCTs for RA. The lessebo effect has potential implications for the development of new treatments and appraisal of current treatment options for RA.
34966765 TELERA-Asynchronous TELEmedicine for Patients With Rheumatoid Arthritis: Study Protocol fo 2021 Innovative strategies are needed to adequately assess and monitor disease activity of patients with rheumatoid arthritis (RA) in times of scarce appointments. The aim of the TELERA study is to evaluate the feasibility and performance of asynchronous telemedicine visits based on patient-generated data and patient's drug history. RA patients use a medical app, ABATON, that captures the results of a self-performed quick CRP-test, joint-count, and electronic patient-reported outcomes in between visits. This is a prospective, multi-center, randomized controlled trial performed in four German university centers. The estimated sample size is 120 patients. The main outcome is the agreement of rheumatologists' treatment decisions based on asynchronous telemedicine patient-generated data with traditional in-person rheumatology clinic-based decisions and with patient suggestions. The TELERA trial will provide evidence regarding the implementation of remote care in rheumatology. Clinical Trial Registration: This clinical trial was registered at German Registry for Clinical Trials (DRKS). http://www.drks.de/DRKS00016350, identifier: DRKS00024928.
34131545 Dairy Consumption: Does It Make an Impact on Self-Reported Disease Activity of Inflammator 2021 May 13 Background As researchers and the public become more cognizant of the impacts of diet and nutrition on health, continued research is needed to provide evidence to support dietary claims. At present, there exists mixed reporting on the effects of dairy consumption and disease activity of inflammatory arthritis (IA). Objective This study attempts to advance current research on the relationship between dairy consumption and self-reported disease activity in patients with IA and to investigate whether dietary modifications can be helpful as a conservative, cost-effective, and accessible supplement to established treatments. Methods Participants completed a modified diet history questionnaire (DHQ), which assessed dairy consumption over the past year, and a Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire, which assessed a participants' self-reported inflammatory disease activity. DHQ and RAPID3 were analyzed using a Pearson product-moment partial correlation to assess variables' relationships. Participants completed the questionnaire in the setting of a rheumatology clinic. Two hundred and four participants were recruited for this study. All of the participants were at least 18 years of age, capable of giving informed consent, and were formally diagnosed with either rheumatoid arthritis or psoriatic arthritis by a board-certified rheumatologist.  Results The results from the questionnaires found that dairy consumption does not contribute to self-reported IA disease activity. While 11 of the 16 DHQ variables maintained a positive correlation with the overall RAPID3 scores, none of these possessed statistical significance. Only when controlling for age and sex did the study find two statistically significant variable correlations between the quantity of milk consumed as a beverage (r=0.147, n=193, p=0.043) and milk added to cereal (r=0.170, n=189, p=0.019) with the RAPID3 scores. Conclusion In summation, the study found no notable correlation between dairy consumption and patients' self-reported IA disease activity.
33197269 Systemic overexpression of interleukin-22 induces the negative immune-regulator SOCS3 and 2021 Apr 6 OBJECTIVE: High levels of IL-22 are present in serum and synovial fluid of patients with RA. As both pro- and anti-inflammatory roles for IL-22 have been described in studies using animal models of RA, its exact function in arthritis remains poorly defined. With this study we aimed to further unravel the mechanism by which IL-22 exerts its effects and to decipher its therapeutic potential by overexpression of IL-22 either locally or systemically during experimental arthritis. METHODS: CIA was induced in DBA-1 mice by immunization and booster injection with type II collagen (col II). Before arthritis onset, IL-22 was overexpressed either locally by intra-articular injection or systemically by i.v. injection using an adenoviral vector and clinical arthritis was scored for a period of 10 days. Subsequently, joints were isolated for histological analysis of arthritis severity and mRNA and protein expression of various inflammatory mediators was determined in the synovium, spleen and serum. RESULTS: Local IL-22 overexpression did not alter arthritis pathology, whereas systemic overexpression of IL-22 potently reduced disease incidence, severity and pathology during CIA. Mice systemically overexpressing IL-22 showed strongly reduced serum cytokine levels of TNF-α and macrophage inflammatory protein 1α that correlated significantly with the enhanced expression of the negative immune regulator SOCS3 in the spleen. CONCLUSION: With this study, we revealed clear anti-inflammatory effects of systemic IL-22 overexpression during CIA. Additionally, we are the first to show that the protective effect of systemic IL-22 during experimental arthritis is likely orchestrated via upregulation of the negative regulator SOCS3.
34241691 Placebo and nocebo responses in randomized controlled trials of non-tumor necrosis factor 2021 Jul 9 OBJECTIVE: This study evaluated the frequency and magnitude of placebo and nocebo responses in placebo-controlled RCTs of non-tumor necrosis factor (TNF) biologics and Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) patients with insufficient response to TNF inhibitors. METHODS: A meta-analysis on rates of placebo response, adverse effects (AEs), severe AEs (SAEs), and withdrawal due to AEs in placebo-controlled RCTs of non-TNF biologics and JAK inhibitors in patients with RA and an insufficient response to TNF inhibitors was conducted. RESULTS: In 9 RCTs containing 3442 patients the pooled incidence of ACR20 response rate in placebo-treated patients was 22.1 (95% CI 16.4-29.1%) and 27.9% (95% CI 24.5-31.6%) in RCTs of non-TNF and JAK inhibitors, respectively. Strong negative correlation was observed between ACR20 response and AE rates in the placebo arm, indicating that the greater the placebo response, the weaker the nocebo response (r = -0.762, P = 0.017). Strong positive correlation was observed between ACR20 response in the placebo and active comparator arms, indicating that the greater the placebo response, the greater the treatment response (r = 0.737, P = 0.003). The pooled estimate in placebo-treated patients with ≥1 AE was 71.8 (95% CI 57.4-82.7%) and 58.7% (95% CI 52.8-64.3%) in RCTs of non-TNF and JAK inhibitors, respectively. The pooled estimate in placebo-treated patients withdrawing due to an AE was 3.8 (95% CI 2.7-5.3%) and 4.0% (95% CI 2.7-6.0%) in RCTs of non-TNF and JAK inhibitors, respectively. Strong positive correlation was observed between AE rates in the placebo and active arms, indicating that the greater the nocebo response, the stronger the AE rate in the active arm (r = 0.855, P = 0.003). CONCLUSION: There were higher placebo and less nocebo effects of JAK vs. non-TNF inhibitors in RA patients with an insufficient response to TNF inhibitors, and the greater the placebo response, the weaker the nocebo response and the greater the efficacy.
35141482 Assessment of the frequency of tarsal tunnel syndrome in rheumatoid arthritis. 2021 Dec OBJECTIVES: In this study, we aimed to determine the frequency of tarsal tunnel syndrome (TTS) in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: Thirty RA patients (1 male, 29 females; mean age: 41.9±10.1 years; range, 26 to 65 years) who met the American College Rheumatology (ACR) classification criteria and 20 healthy volunteers (1 male, 19 females; mean age: 39.3±10.8 years; range, 26 to 60 years) without any complaints between August 2006 and October 2007 were included in the study. Demographic characteristics of the study group were assessed and neurological examinations were performed. The Tinel's sign was checked to provoke the TTS symptoms. Disease severity was measured using Visual Analog Scale (VAS), Disease Activity Score-28 (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The health-related quality of life and disability status were determined using the Health Assessment Questionnaire (HAQ), Short Form 36 (SF-36), Foot Function Index (FFI), and VAS (0-100 mm). The positional relationship of the foot pain was questioned with VAS. The 100-m walking distance of the patient and control groups were calculated. RESULTS: Bilateral TTS was detected in 10 of the patients (33.3%) with rheumatoid arthritis. No relationship with the TTS disease duration, seropositivity, rheumatoid nodule, joint deformities, corticosteroid use, and DAS28 score were found. In correlation with TTS, foot and ankle joint were the first involved joints at the beginning of RA disease (p<0.005). The Tinel's sign was found to be 45% positive in patients with TTS. The 100-m walking time was significantly longer in RA patients compared to the control group (p<0.0001). CONCLUSION: Tarsal tunnel syndrome is commonly seen in RA and its incidence increases in patients with primary foot involvement. Therefore, caution should be taken against the entrapment neuropathies in these patients, and they should be supported by electrophysiological practices, when the diagnosis is necessary.