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ID PMID Title PublicationDate abstract
31820725 Combined manual and automated immunophenotypisation identified disease-specific peripheral 2020 Sep OBJECTIVES: Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation. METHODS: Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations. Cell activation, proliferative capability and osteoclastogenic effects were tested in vitro. Comparison with synovial compartment, clinical data and anti-TNF treatment were added to peripheral blood analysis. RESULTS: PsA had lower double-negative T-cell frequency, while RA had lower double-positive T-cell frequency and expanded Th1-like and cytotoxic T-cell subsets. CD32B expression was increased on naïve and memory B-cells in AS and associated with disease activity. CCR6+ and CXCR5+ cytotoxic T-cells and CD32B+ naïve and memory B-cells were highly enriched within the synovial compartment. T-cells and B-cells from AS exhibited enhanced activation and proliferation in vitro, whereas T-cell conditioned medium from RA produced an increased osteoclastogenic effect. CCR1 and CXCR4 were upregulated on osteoclastogenic monocyte subsets of RA, AS and PsA patients. Bioinformatic Citrus analysis identified additional T-cell, B-cell and monocyte clusters specifically associated with each disease. CONCLUSIONS: By combining manual and automated data analysis, our study revealed several disease-specific immune cell subpopulations, particularly cytotoxic T-cell subsets in RA and memory B-cell subsets in AS, which may serve as an indicator of active disease or possible therapeutic target.
30963993 Cigarette smoking and clinical response to certolizumab pegol treatment in Hungarian, Czec 2019 Nov OBJECTIVES: Smoking has been shown to influence rheumatoid arthritis (RA) severity and reduce response to some anti-tumour necrosis factor (anti-TNF) therapies. CIMDORA assessed the association between cigarette smoking and clinical effectiveness of certolizumab pegol (CZP) in Hungarian, Slovak, and Czech RA patients. METHODS: CIMDORA was a prospective, non-interventional, 104-week study (Feb 2011-Aug 2015). The primary endpoint was association between change in 28-joint Disease Activity Score (DAS28[ESR]) from baseline to Week 12, and baseline cigarette pack-year history. Secondary endpoints included association between change in DAS28(ESR) and daily number of cigarettes smoked. The full analysis set (FAS) included all patients receiving ≥1 dose of CZP with all necessary assessments for the primary endpoint. Treatment-emergent adverse events (TEAEs) were reported for all patients receiving ≥1 dose of CZP. RESULTS: The FAS included 218/273 enrolled patients: 155 Hungarian, 46 Czech and 17 Slovak. Hungarian and Czech patients completed 104 weeks (n=141); Slovak patients completed 52 weeks. Mean change in DAS28(ESR) [SD] at Week 12 (-2.78 [1.47]) was not significantly associated with baseline cigarette pack-year history (slope estimate [SE]: 0.03, 95% confidence interval [CI]: -0.16, 0.21 [p=0.77]). Mean DAS28(ESR) [SD] reductions to Week 52 (-3.33 [1.33]) were not significantly associated with daily number of cigarettes smoked in the previous month (SE: 0.001, CI: -0.05, 0.05 [p=0.95]). Two deaths were reported but neither of them was related to CZP. No new safety signals were identified and the safety profile was consistent with previous CZP studies. CONCLUSIONS: After 104 weeks of CZP treatment, patients demonstrated similar DAS28(ESR) improvements, irrespective of smoking history.
31416921 Patients with Rheumatoid Arthritis Acquire Sustainable Skills for Home Monitoring: A Prosp 2020 May 1 OBJECTIVE: In an eHealth setting, to investigate intra- and interrater reliability and agreement of joint assessments and Disease Activity Score using C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA) and test the effect of repeated joint assessment training. METHODS: Patients with DAS28-CRP ≤ 5.1 were included in a prospective cohort study (clinicaltrials.gov: NCT02317939). Intrarater reliability and agreement of patient-performed joint counts were assessed through completion of 5 joint assessments over a 2-month period. All patients received training on joint assessment at baseline; only half of the patients received repeated training. A subset of patients was included in an appraisal of interrater reliability and agreement comparing joint assessments completed by patients, healthcare professionals (HCP), and ultrasonography. Cohen's κ coefficients and intraclass correlation coefficients (ICC) were used for quantifying of reliability of joint assessments and DAS28-CRP. Agreement was assessed using Bland-Altman plots. RESULTS: Intrarater reliability was excellent with ICC of 0.87 (95% CI 0.83-0.90) and minimal detectable change of 1.13. ICC for interrater reliability ranged between 0.69 and 0.90 (good to excellent). Patients tended to rate DAS28-CRP slightly higher than HCP. In patients receiving repeated training, a mean difference in DAS28-CRP of -0.08 was observed (limits of agreements of -1.06 and 0.90). After 2 months, reliability between patients and HCP was similar between groups receiving single or repeated training. CONCLUSION: Patient-performed assessments of joints and DAS28-CRP in an eHealth home-monitoring solution were reliable and comparable with HCP. Patients can acquire the necessary skills to conduct a correct joint assessment after initial and thorough training. [clinicaltrials.gov (NCT02317939)].
31753588 CXCL16/CXCR6 axis promotes bleomycin-induced fibrotic process in MRC-5 cells via the PI3K/ 2020 Apr OBJECTIVE: Interstitial lung disease (ILD) is a progressive and irreversible lung disease with very limited therapeutic options. Previous studies have found that chemokine ligands CXCL16 and CXCR6 play critical roles in organ fibrosis. However, whether CXCL16 and CXCR6 are also involved in the pathogenesis of ILD, as well as their regulatory role in pulmonary fibrosis, has not been reported. METHODS: In this study, we detected CXCL16 levels in patients with rheumatoid arthritis-associated ILD (RA-ILD) and examined the critical role of the CXCL16/CXCR6 axis in the proliferation and collagen production of human pulmonary fibroblasts (MRC-5 cells). The effect of anti-CXCL16 antibody on the bleomycin-induced fibrogenesis in cultured MRC-5 cells was also evaluated. RESULTS: Our results indicated that serum soluble CXCL16 was significantly higher in RA-ILD patients and also associated with the severity of lung fibrosis. CXCL16 facilitates fibrosis by enhancing proliferation, migration, and collagen production of MRC-5 cells. Furthermore, a synergistic fibrogenic effect of CXCL16 and bleomycin has been found. CXCL16 stimulated the activation of PI3K/AKT/FOXO3a signaling pathway in MRC-5 cells, and the inhibition by specific inhibitors Wortmannin and LY294002, or knockdown of CXCR6 by siRNA also suppressed the biological functions of MRC-5 cells mediated by CXCL16. Similarly, down-regulation of CXCR6 also partly blocked BLM-induced fibrogenesis in MRC-5 cells. CONCLUSIONS: CXCL16/CXCR6 axis promotes proliferation and collagen production of MRC-5 cells by the PI3K/AKT/FOXO3a signaling pathway, and inhibition of the CXCL16/CXCR6 axis may provide a new therapeutic strategy targeting pulmonary fibrosis.
31619287 High prevalence of obesity in rheumatoid arthritis patients: association with disease acti 2019 Oct 16 INTRODUCTION: Rheumatoid arthritis (RA) is a well-documented independent risk factor for cardiovascular disease. Obesity may provide an additional link between inflammation and accelerated atherosclerosis in RA. OBJECTIVE: To evaluate the association between obesity and disease parameters and cardiovascular risk factors in RA patients. METHOD: Cross-sectional study of a cohort of RA patients from three Brazilian teaching hospitals. Information on demographics, clinical parameters and the presence of cardiovascular risk factors was collected. Blood pressure, weight, height and waist circumference (WC) were measured during the first consultation. Laboratory data were retrieved from medical records. Obesity was defined according to the NCEP/ATPIII and IDF guidelines. The prevalence of obesity was determined cross-sectionally. Disease activity was evaluated using the DAS28 system (remission < 2.6; low 2.6-3.1; moderate 3.2-5.0; high > 5.1). RESULTS: The sample consisted of 791 RA patients aged 54.7 ± 12.0 years, of whom 86.9% were women and 59.9% were Caucasian. The mean disease duration was 12.8 ± 8.9 years. Three quarters were rheumatoid factor-positive, the mean body mass index (BMI) was 27.1 ± 4.9, and the mean WC was 93.5 ± 12.5 cm. The observed risk factors included dyslipidemia (34.3%), type-2 diabetes (15%), hypertension (49.2%) and family history of premature cardiovascular disease (16.5%). BMI-defined obesity was highly prevalent (26.9%) and associated with age, hypertension and dyslipidemia. Increased WC was associated with diabetes, hypertension, dyslipidemia and disease activity. CONCLUSION: Obesity was highly prevalent in RA patients and associated with disease activity.
30933423 Malondialdehyde-Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis-Associ 2019 Sep OBJECTIVE: To compare serum anti-malondialdehyde-acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) to those found in controls. METHODS: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. RESULTS: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11-3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19-4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. CONCLUSION: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.
32421968 Mast Cells Mediate Rheumatoid Arthritis-Inhibitory Role of IL-37. 2019 Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several proinflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF). IL-1 induces TNF and vice versa, causing joint damage and cartilage degradation. Current antirheumatic drugs may be effective, but they possess many unwanted side effects. In recent years, inhibitors of proinflammatory cytokines have increasingly entered mainstream clinical practice. Recent evidence indicates that IL-37, which has anti-inflammatory properties, is increased in the serum and is released from white blood cells in patients with RA. Mast cells (MCs), stimulated by the neuropeptide substance P (SP) and IL-33, release IL-1β and TNF. Recent evidence indicates that large amounts of IL-1β and TNF can be released from human MCs, which also secrete CXCL8, which promotes migration of immune cells, causing erosion of the bone and cartilage. Treatment with IL-37 can block the MC stimulation and release of inflammatory compounds, attenuating the severity of the disease and/or altering its progression.
29853189 Identifying MRI-detected inflammatory features specific for rheumatoid arthritis: two-fold 2019 Feb OBJECTIVE: MRI-detected inflammation is considered of diagnostic value for rheumatoid arthritis (RA), but its evaluation involves a time-consuming scoring of 61 joint-level features. It is not clear, however, which of these features are specific for RA and whether evaluating a subset of specific features is sufficient to differentiate RA patients. This study aimed to identify a subset of RA-specific features in a case-control setting and validate them in a longitudinal cohort of arthralgia patients. METHODS: The difference in frequency of MRI-detected inflammation (bone marrow edema, synovitis, and tenosynovitis) between 199 RA patients and 193 controls was studied in 61 features across the wrist, metacarpophalangeal, and metatarsophalangeal joints. A subset of RA-specific features was obtained by applying a cutoff on the frequency difference while maximizing discriminative performance. For validation, this subset was used to predict arthritis development in 225 clinically suspect arthralgia (CSA) patients. Diagnostic performance was compared to a reference method that uses the complete set of 61 features normalized for inflammation levels in age-matched controls. RESULTS: Subset of 30 features, mainly (teno)synovitis, was obtained from the case-control setting. Validation in CSA patients yielded an area of 0.69 (95% CI: 0.59-0.78) under the ROC curve and a positive predictive value (PPV) of 31%, compared to 0.68 (95% CI: 0.60-0.77) and 29% PPV of the reference method with 61 features. CONCLUSION: Subset of 30 MRI-detected inflammatory features, dominated by (teno)synovitis, offers a considerable reduction of scoring efforts without compromising accuracy for prediction of arthritis development in CSA patients.
31237785 Real-world utilization of methotrexate or prednisone co-therapy with etanercept among Cana 2019 Nov Objective: To evaluate whether initiation of etanercept therapy among patients with rheumatoid arthritis (RA) impacts use of co-therapy with methotrexate or prednisone, and to describe etanercept dosing dynamics compared to product monograph in the Canadian real-world setting. Methods: A retrospective cohort study was conducted using claims-level data from IQVIA Private Drug Plan database, Ontario Public Drug Plan database and Régie de l'assurance maladie du Québec database. Bio-naïve RA patients initiating etanercept between July 2014 and June 2015 were identified and their claims for methotrexate or prednisone were analyzed. Utilization of methotrexate or prednisone was calculated as average weekly dose in milligrams, and compared in the 6 months pre-initiation versus 12 months post-initiation of etanercept. Weekly etanercept dosing of each patient was calculated and analyzed to determine whether patients had at least 20% higher or lower average dose than monograph recommended dose (50 mg/week), and were then flagged as above-monograph or below-monograph, respectively. Results: A total of 2876 patients with RA (66% female, 76% aged 18-65) were included; 62% (n = 1,140) used methotrexate and 27% used prednisone (n = 498) both pre- and post-initiation of etanercept. In methotrexate patients, the average weekly dose dispensed was 25.4 mg in the 6 months pre-etanercept, and 25.0 mg in the 12 months post-etanercept initiation (p = .5282). In prednisone patients, the average weekly dose dispensed reduced from 122.6 mg pre-etanercept to 107.1 mg post-etanercept initiation (p = .2173). Among patients who were already on methotrexate or prednisone, after initiating on etanercept 16% (n = 213) and 34% (n = 254) of patients stopped methotrexate and prednisone, respectively. When compared to the recommended dose, 12% (n = 168) of patients were below-monograph and 7.1% of patients were above-monograph during their first year of etanercept therapy. Average etanercept dosing was consistently lower than product monograph during the follow-up year. Conclusions: Patients had a modest but not statistically significant decrease in prescribed doses of co-therapy with methotrexate and prednisone when etanercept was added to patients' therapy. In addition, 12-14% of patients stopped their co-therapy with methotrexate or prednisone. Further study is needed to understand the impact on patient outcomes and safety.
30324407 Increased risk of sudden sensory neural hearing loss in patients with rheumatoid arthritis 2019 Mar To evaluate the association between sudden sensorineural hearing loss (SSNHL) and rheumatoid arthritis (RA) among a national sample cohort from Korea. Data were collected from 2002 through 2013 for individuals aged ≥ 20 years in the Korean National Health Insurance Service (NHIS)-National Sample Cohort. We extracted the data from RA patients (n = 7619) and 1:4-matched controls (n = 30,476) and analyzed the occurrence of SSNHL. Matching was performed based on age, sex, income, region of residence, and medical history. RA was diagnosed based on International Classification of Disease-10 (ICD-10) codes (M05 or M06) and prescriptions for the antirheumatic drugs. SSNHL was diagnosed based on the relevant ICD-10 code (H912). Among the SSNHL participants, we included only those who had undergone an audiometry exam (claim codes: E6931-E6937, F6341-F6348) and received treatment with steroids. The crude and adjusted hazard ratios (HRs) were calculated using Cox-proportional hazard models, and the 95% confidence intervals (CIs) were determined. Subgroup analyses based on age and sex were also performed. The rate of SSNHL in the RA group (0.8% [62/7619]) was higher than that in the control group (0.6% [177/30,476], P = 0.021). The crude and adjusted HRs for SSNHL were 1.40 (95% CI = 1.05-1.87) and 1.39 (95% CI = 1.04-1.86), respectively, in the RA group (each P < 0.05). The relationship between RA and SSNHL was observed primarily in patients aged ≥ 50 years and men. The risk of SSNHL is higher in patients with RA.
31290023 Patient satisfaction and outcomes of partial wrist denervation in inflammatory arthritis. 2019 Nov INTRODUCTION: Inflammatory arthritis frequently affects the wrist, resulting in pain and disability. This study aims to investigate the long-term outcome of patients who underwent posterior interosseous nerve (PIN) denervation for inflammatory arthritis of the wrist. METHOD: xForty consecutive wrists (36 patients) treated with PIN denervation were identified (mean follow-up 47 months; mean age 62.6 years, 77.5% female). Pain and function scores were objectively measured using the patient-rated wrist-evaluation (PRWE) questionnaires. Data was compared for pre-operation and post-operation (early and long term). The Student's t test was used to compare differences between groups for continuous data, whilst the sign test was utilised for pairwise comparisons. The p value was set at 0.05 for all comparisons. RESULTS: Three patients died during the course of this study from causes unrelated to wrist surgery, resulting in 93% follow-up. PRWE questionnaires demonstrated a significant improvement following PIN denervation (median pain pre-op 42 vs post-op 16 (p < 0.001); median function pre-op 82 vs post-op 41 (p < 0.001), respectively). There were no differences identified between early and long-term post-operative scores. Four cases (10%) had persistent, ulnar-based pain and required secondary salvage wrist arthrodesis. However, 95% of patients remained "very satisfied" or "satisfied" after surgery. CONCLUSIONS: This study highlights the effectiveness of PIN denervation as a simple alternative to wrist arthrodesis due to long-term improvement in pain and preservation of function. We recommend this procedure in the presence of a positive diagnostic PIN infiltration test to avoid wrist arthrodesis for as long as possible. In patients with predominantly ulnar-based wrist pain, the outcome is less predictable and this subgroup of patients should be counselled about the possibility of subsequent salvage wrist fusion. Key Points • One of the largest study cohorts which report on the outcome of the wrist PIN denervation procedure with over 2-year follow-up • Clinical outcomes of success are enhanced with the use of validated, objective patient-reported outcome measures relating to overall satisfaction, pain relief and function. • Long-term outcomes are compared to pre-operative and immediate post-operative outcome scores, demonstrating the benefits of PIN denervation and the longevity it provides.
32186112 Alkaloids, flavonoids, polyphenols might be responsible for potent antiarthritic effect of 2019 Oct OBJECTIVE: To evaluate in vitro and in vivo antiarthritic potential of Solanum nigrum (S. nigrum). METHODS: Aqueous methanolic (70∶30) extract of S. nigrum was prepared. The in vitro antiarthritic effect was evaluated in terms of its inhibition of protein denaturation and membrane stabilization. While, formaldehyde, complete Freund's adjuvant (CFA) and Collagen induced arthritis rat models were used to study in vivo antiarthritic activities of S. nigrum at dose level of 200, 400 and 800 mg/kg. RESULTS: The extract exhibited inhibition of protein denaturation and protected red blood cell by stabilizing the membranes in a concentration dependent manner, with maximum effect attained at 800 μg/mL. Moreover, there was a marked reduction in paw edema observed in extract treated animals, when compared to arthritic control animals in all in vivo models and 800 mg/kg dose got maximum reduction of paw edema. In CFA and collagen models, plant extract restored body weight, hematologic parameters, radiographic and histopathologic alterations towards normal. CONCLUSION: It could be concluded that S. nigrum holds antiarthritic potential, supporting its traditional use in treatment of rheumatoid arthritis.
31037071 Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance 2019 Objectives: Most DAMPs in inflammatory diseases are TLR2- and TLR4-ligands and according to the current concept, repeated stimuli would result in tolerance. Aims of the study were to verify this assumption, to investigate whether epigenetic effectors are involved and to explore the situation in rheumatoid arthritis (RA). Methods: A trained immunity (TI) and tolerance protocol was established using peripheral blood monocytes from healthy donors, β-glucan and lipopolysaccharide (LPS). The training or tolerance capacities of RA-relevant DAMPs were tested. Results: β-Glucan-, oS100A4-, HMBG1-, and HSP90-pretreated monocytes showed increased IL-6 responses to LPS re-stimulation. β-Glucan, oS100A and tenascin C induced training of monocytes to release more TNFα. In comparison to β-glucan, most DAMPs tested induced less TI, with exception of oS100A4. Monocytes exposed to oS100A4 showed increased IL-1β, IL-6, and TNFα in response to LPS, in spite that both stimulate TLR4. RNASEq upon β-glucan or oS100A4 revealed similar changes in chemokines/cytokines and epigenetic effectors; 17 epigenetic effectors correlated with chemokine/cytokine gene expression; PRDM8 was associated with more chemokine and cytokine transcripts. Knockdown of PRDM8 abolished TI induced by oS100A4. In RA, plasma S100A4 correlated with increased CSF2, and increased PRDM8 transcription in RA monocytes was associated with increased plasma CCL5 and IL-6, as well as therapy-resistance. Conclusion: Bypass of tolerance by DAMPs might be a phenomenon as important as TI, since it could explain how chronic inflammation can be maintained in spite of an environment with multiple TLR2/TLR4-ligands. In RA monocytes, a PRDM8-dependent TI mechanism could be responsible for sustained chemokine/cytokines levels.
30893475 Autoreactive B-lymphocytes in SLE and RA patients: Isolation and characterisation using ex 2019 Jul Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B-cell hyperactivation and production of autoantibodies (AutoAbs) against various self-antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody-secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto-reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen-specific and citrullinated peptide-specific auto-reactive B lymphocytes by magnetic selection with ENA- and citrullinated peptide-bound immunobeads. We obtained blood auto-reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy-chain variable regions. Their presence correlated with serum levels of autoAb. Auto-reactive B lymphocytes were able to differentiate into auto-reactive antibody-secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto-reactive B cells and/or antibody-secreting cells, four different profiles were described in lupus patients. Thus, tracking auto-reactive B cells and/or antibody-secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients.
30376130 Exposure-response analyses demonstrate no evidence of interleukin 17A contribution to effi 2019 Feb 1 OBJECTIVES: ABT-122 is a dual-variable-domain immunoglobulin that neutralizes both TNF-α and IL-17A. The objective of this work was to characterize exposure-response relationships for ABT-122 relative to adalimumab (TNF-α inhibitor) using ABT-122 phase 2 trials in patients with RA or PsA. METHODS: Patients received subcutaneous doses of ABT-122 ranging from 60 mg every other week (EOW) to 240 mg every week, adalimumab 40 mg EOW, or placebo (PsA patients only) for 12 weeks. Relationships between ABT-122 or adalimumab serum concentrations and time course of ACR20, ACR50 and ACR70 and PASI50, PASI75 and PASI90 responses were characterized using a non-linear mixed-effects Markov modelling approach. RESULTS: A total of 221 RA patients and 240 PsA patients were included in the analyses. At comparable molar exposures, there was no differentiation of efficacy between ABT-122 and adalimumab and there were no consistent differences between ABT-122 and adalimumab in the potency estimates for different efficacy endpoints based on the Markov models. Plateau of ABT-122 efficacy was achieved at exposures associated with the 120 mg EOW dose in patients with RA, which were comparable to molar exposures of adalimumab 40 mg EOW, and at the lowest dose of 120 mg every week in patients with PsA. CONCLUSION: The exposure-response relationships for ABT-122 were not distinguishably different from those of adalimumab in patients with RA or PsA. Overall, there was no clear evidence that inhibition of the IL-17 pathway provided incremental benefit in the presence of TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02433340, NCT02349451.
31777181 Interactions between women with rheumatoid arthritis and nurses during outpatient consulta 2019 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease, and patients with RA receive services in various settings-for example, in nurse-led follow-up consultations. The present study aimed to investigate how the management of RA in everyday life is expressed in interactions between nurses and women with RA during nursing consultations. METHODS: The study was conducted in accordance with constructivist grounded theory, with data based on participant observations and subsequent interviews with 10 women with RA. RESULTS: A core category was developed, "Collaboration through mutual acknowledgement", which documented how the women and nurses confirmed their shared understanding of the content and the structure of the consultation. Three subcategories were identified: (i) "On safe ground", which illustrated that biomedical factors, such as blood test results and pharmacological treatment, structured the basis of the dialogue; (ii) "Venturing forward", which documented how both parties were aware of each other's reactions when the dialogue dealt with women's perspectives of illness in their everyday lives; and (iii) "Gentle steering", which showed that the nurses gently steered the dialogue if the women strayed from the planned content. CONCLUSIONS: Both parties agreed that a disease perspective consistent with biomedical factors formed the basis for further dialogue. Subsequently, the women's perspectives on illness were included, and the women felt acknowledged. Therefore, the recommendation is that the consultations start by all parties agreeing on a shared agenda to facilitate the inclusion of the women's perspectives on illness.
31699430 Tc-99m hydroxymethylene diphosphonate SPECT/CT for the evaluation of osteonecrosis of the 2020 Jan AIM: To investigate the diagnostic ability of maximum standardised uptake value (SUV(max)) at combined single-photon-emission computed tomography/computed tomography (SPECT/CT) for the evaluation of osteonecrosis of the jaw. MATERIALS AND METHODS: Seven patients with mandibular osteonecrosis (three osteoradionecrosis, three medication-related osteonecrosis of the jaw (MRONJ), and one rheumatoid arthritis) underwent SPECT/CT at 4 hours after injection of technetium 99m hydroxymethylene diphosphonate. The SPECT/CT parameters SUV(max) were compared for the osteonecrosis with normal mandible. Statistical analyses among the SUV(max) of osteonecrosis were performed by one-way repeated measures analysis of variance with Tukey's HSD (honestly significant difference) test. A p-value <0.05 was considered statistically significant. RESULTS: SUV(max) for MRONJ and rheumatoid arthritis (23.24±8.63) were significantly higher than those for osteoradionecrosis (9.05±1.39, p=0.005) and normal mandible (3.57±0.46, p=0.000). CONCLUSIONS: SUV(max) derived from bone SPECT/CT could be useful for the evaluation of osteonecrosis of the jaw.
30092680 The three-year efficacy of iguratimod in clinical daily practice in patients with rheumato 2019 Sep Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.
30642076 TNF-α Inhibitors Decrease Classical CD14(hi)CD16- Monocyte Subsets in Highly Active, Conv 2019 Jan 12 Monocytes are pivotal cells in inflammatory joint diseases. We aimed to determine the effect of TNF-α inhibitors (TNFi) on peripheral blood monocyte subpopulations and their activation in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients with high disease activity. To address this, we studied 50 (32 AS, 18 RA) patients with highly active disease with no prior history of TNFi use who were recruited and assigned to TNFi or placebo treatment for 12 weeks. Cytometric and clinical assessment was determined at baseline, four, and 12 weeks after initiation of TNFi treatment. We observed that treatment with TNFi led to a significant decrease in CD14(hi)CD16- monocytes in comparison to placebo, while circulating CD14(dim)CD16+ monocytes significantly increased. The TNFi-induced monocyte subset shifts were similar in RA and AS patients. While the percentage of CD14(dim)CD16+ monocytes increased, expression of CD11b and CD11c integrins on their surface was significantly reduced by TNFi. Additionally, CD45RA+ cells were more frequent. The shift towards nonclassical CD14(dim)CD16+ monocytes in peripheral blood due to TNFi treatment was seen in both AS and RA. This may reflect reduced recruitment of these cells to sites of inflammation due to lower inflammatory burden, which is associated with decreased disease activity.
30953327 Cardiovascular Disease Risk in Older Adults and Elderly Patients with Rheumatoid Arthritis 2019 Jun The prevalence of rheumatoid arthritis (RA), the most common autoimmune inflammatory arthritis, is increasing, partly due to the aging of the general population. RA is an independent risk factor for the development of cardiovascular disease (CVD). Older adults and elderly patients with RA develop CVD at a younger age compared with their general population peers. Both the traditional cardiovascular risk factors (age, sex, smoking, diabetes mellitus, hypertension), and systemic inflammation (i.e. high disease activity) are contributors to accelerated CVD in people with RA. Of the disease-modifying antirheumatic drugs (DMARDs) used for RA treatment, methotrexate, triple combination oral therapy (methotrexate, sulfasalazine, and hydroxychloroquine), tumor necrosis factor inhibitor biologicals, and abatacept have the strongest data in favor of the reduction of cardiovascular events in patients with RA. A treat-to-target strategy should be employed in older adults and elderly patients with RA to ensure appropriate reduction in cardiovascular risk, which can also prevent short- and long-term musculoskeletal disability. Our review findings are in line with the 2016 European League Against Rheumatism guideline recommendations, specifically: (1) RA disease activity should be controlled with an optimal DMARD regimen using a treat-to-target approach; (2) the lipid profile should be assessed and monitored in every older adult and elderly RA patient; (3) CVD risk factors, including smoking cessation, blood pressure, and blood glucose control, should be optimized; (4) RA treatment should be initiated as soon as possible; and (5) shared decision making regarding the treatment of patients with RA should include a discussion on the potential amelioration of increased cardiovascular risk.