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ID PMID Title PublicationDate abstract
32053642 Intake frequency of vegetables or seafoods negatively correlates with disease activity of 2020 OBJECTIVE: To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS: This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS: 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (β = -0.15, p<0.01), SDAI (β = -0.18, p<0.001), MMP-3 (β = -0.15, p<0.01), and HAQ (β = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (β = -0.11 p<0.05), MMP-3 (β = -0.12, p<0.01), and HAQ (β = -0.11, p<0.05). CONCLUSIONS: These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.
32174196 The safety of baricitinib in patients with rheumatoid arthritis. 2020 May Introduction: Despite improvement in disease outcomes and prognosis, a substantial number of patients with rheumatoid arthritis (RA) still require a novel agent for effective treatment. Baricitinib is a targeted synthetic disease-modifying antirheumatic drug (tsDMARDs) that selectively inhibits Janus kinase (JAK1/JAK2), an important enzyme in the pathogenesis of RA.Areas covered: This paper aimed to evaluate the pharmacodynamics and pharmacokinetics of baricitinib while reviewing its safety and efficacy in the treatment of RA.Expert opinion: Randomized controlled trials of baricitinib showed its efficacy and safety in patients with active RA who were methotrexate (MTX)-naïve or were not adequately responsive to MTX, conventional synthetic DMARDs, or tumor necrosis factor inhibitors. Baricitinib may be suitable in patients who prefer oral therapy and do not have a history of severe renal impairment, recent history of malignancy, or risk factors for adverse events (AEs) such as venous thromboembolism, opportunistic infection, and diverticulitis. Dose adjustment of baricitinib, based on the assessment of patient conditions including their renal function and disease activity, is an important strategy for successful and safe treatment. However, long-term post-marketing surveillance studies with a larger sample size are required to evaluate the overall safety and AEs with low incidence rates in clinical settings.
32531504 Cumulative patient-based disease activity monitoring in rheumatoid arthritis - predicts su 2020 Aug OBJECTIVE: Patient-based Disease Activity Score 2 (PDAS2) had been developed for RA patients to self-assess and record disease activity in between clinic visits. This study explored the clinical utility of time-integrated cumulative PDAS2 (cPDAS2) on predicting sustained remission or low disease activity state (LDAS), flare and treatment escalation. METHODS: We recruited 100 patients to record PDAS2 at home fortnightly between two consecutive clinic visits. Rheumatologists adjusted treatment according to disease activity recorded during clinic consultation while blinded to home PDAS2 scores. cPDAS2 calculated from the area-under-curve of all PDAS2 scores were compared with disease activities at both visits. cPDAS2 and ΔcPDAS2 (change from PDAS2 at the first visit) were tested to determine their ability to predict ACR/EULAR remission, SDAI flare-up (from remission/LDAS to moderate/high disease activity) and treatment escalation. Optimal cut-points were determined by Receiver Operator Characteristic curve. RESULTS: Mean age of the patients was 59 years, mean RA duration 14 years, 90% were female, 71% seropositive and 64% in remission/LDAS. The home PDAS2 completion rate was 92%. PDAS2 scores were done 7.5 times every 15 days over a 16-week follow-up (all medians). The sensitivity of cPDAS2 in predicting Boolean/SDAI remission at two visits, DAS28, SDAI and CDAI remission or LDAS were 93%, 84%, 73% and 80% respectively. cPDAS2 ≥ 0.29 predicted flare (P = 0.04), with specificity 79% and negative predicting value (NPV) 88%. Rheumatologists' decision to escalate treatment was predicted by (cPDAS2 ≥ 4.33 and ΔcPDAS2 ≥ 0.059) (P = 0.007) with specificity 88% and NPV 89%, and (cPDAS2 ≥ 4.33 or ΔcPDAS2 ≥ 0.059) (P = 0.02) with both sensitivity and NPV 100%. CONCLUSION: PDAS2 monitoring at home is feasible. cPDAS2 is useful to predict flare and treatment escalation.
32887976 Transforming clinical trials in rheumatology: towards patient-centric precision medicine. 2020 Oct Despite the success of targeted therapies in the treatment of inflammatory arthritides, the lack of predictive biomarkers drives a 'trial and error' approach to treatment allocation, leading to variable and/or unsatisfactory responses. In-depth characterization of the synovial tissue in rheumatoid arthritis, as well as psoriatic arthritis and spondyloarthritis, is bringing new insights into the diverse cellular and molecular features of these diseases and their potential links with different clinical and treatment-response phenotypes. Such progress raises the tantalizing prospect of improving response rates by matching the use of specific agents to the cognate target pathways that might drive particular disease subtypes in specific patient groups. Innovative patient-centric, molecular pathology-driven clinical trial approaches are needed to achieve this goal. Whilst progress is clearly being made, it is important to emphasize that this field is still in its infancy and there are a number of potential barriers to realizing the premise of patient-centric clinical trials.
32173513 Personalized medicine in rheumatoid arthritis: How immunogenicity impacts use of TNF inhib 2020 May Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay - RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.
33123921 Risk of serious infection, malignancy, or death in Japanese rheumatoid arthritis patients 2021 May To evaluate whether combinatorial use of abatacept (ABT) and tacrolimus (Tac) increases the risk of adverse events compared to their individual use in Japanese rheumatoid arthritis (RA) patients. We conducted a retrospective cohort study of RA patients using the Japanese multicenter database and analyzed the data of RA patients registered from April 2010 to March 2019 by comparing three treatment groups who received Tac, ABT, or a combination of both. We included patients who had initiated treatment with ABT or Tac and excluded patients who used tumor necrosis factor inhibitors, IL-6 inhibitors, and Jak inhibitors in the first year of our study. The primary outcome was the occurrence of adverse events such as infections that required hospitalization, newly diagnosed malignancy, or death from any cause after initiation of ABT or Tac. Of the 27,032 RA patients in the registry, 2009 patients were included. The Tac, ABT, and combination groups consisted of 1328, 563, and 118 patients, respectively. Primary outcome occurred in 149 (13.4%), 62 (13.5%), and 14 (13.9%) patients of the Tac, ABT, and combination groups, respectively. The incidence of adverse events between groups was not significantly different (p = 0.638). A Cox regression analysis which was adjusted for potential confounders such as age, disease activity, and concomitant use of prednisolone revealed no significant differences between groups. The combinatorial use of ABT and Tac, or ABT alone does not increase the risk of adverse events when compared to the use of Tac alone in RA patients in Japan. Key Points • This study included Japanese rheumatoid arthritis data and found that there was no significant risk when patients were treated with a combination of Tac and ABT or each drug alone.
32381123 Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depen 2020 May 7 BACKGROUND: The tumor necrosis factor (TNF) superfamily cytokine TNF-like protein 1A (TL1A) and its receptor DR3 are essential for diverse animal models of autoimmune disease and may be pathogenic in rheumatoid arthritis (RA). However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and other therapies in RA is not clear. METHODS: We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA. RESULTS: Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with other diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions. CONCLUSIONS: TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA.
31969172 Abatacept in rheumatoid arthritis: survival on drug, clinical outcomes, and their predicto 2020 Jan 22 BACKGROUND: There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. METHODS: RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of ≥ 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. RESULTS: There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p < 0.001), with longer survival in bionaïve patients. Men (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.74-0.98) and methotrexate users (HR 0.85, 95% CI 0.76-0.95) were less likely to discontinue abatacept, whereas a high pain score predicted discontinuation (HR 1.14 per standard deviation, 95% CI 1.07-1.20). The absence of previous bDMARD exposure, male sex, and a low HAQ score were independently associated with LUNDEX-corrected EULAR good response. The absence of previous bDMARD exposure also predicted LUNDEX-corrected HAQ response. CONCLUSIONS: In this population-based study of RA, bDMARD naïve patients and male patients were more likely to remain on abatacept with a major clinical response.
31376995 Increased hospitalization rates following heart failure diagnosis in rheumatoid arthritis 2020 Feb OBJECTIVE: To compare the frequency of and trends in hospitalizations after heart failure (HF) diagnosis in patients with and without rheumatoid arthritis (RA) during 1987-2015. METHODS: The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. RESULTS: The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalization rate after HF diagnosis was higher in RA vs non-RA (rate ratio [RR] 1.17; 95%CI 1.08-1.26). Hospitalization rates in both groups have been declining since 2005 and the difference between patients with and without RA may be decreasing after 2010. The magnitude of the increase was similar in both sexes and across all ages. Patients with RA were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF or other cardiovascular causes compared to non-RA patients. CONCLUSIONS: The hospitalization rate following HF diagnosis was higher in RA versus non-RA patients regardless of sex and age. Increased hospitalization risk in patients with RA was driven by increased rates of non-cardiovascular hospitalization.
32376462 Sialic acid-modified chitosan oligosaccharide-based biphasic calcium phosphate promote syn 2020 Jul 10 Therapeutic goals for rheumatoid arthritis (RA) consist of inhibiting the inflammatory response and repairing the damaged bone/cartilage. Tissue engineering could achieve both goals, however, it was hindered due to the lack of biologically relevant tissue complexity, limitation in covering the entire polyarthritis lesions and requirement of extra surgical implantation. Integrating nanotechnologies into clinically sized implants represents a major opportunity to overcome these problems. Herein, we designed a sialic acid (SA)-modified chitosan oligosaccharide-based biphasic calcium phosphate (BCP), a biomimetic nanoplatform that could load with methotrexate. We found that SA modification could not only improve the accumulation of the designed organic-inorganic nanoplatform in arthritic paws (34.38% higher than those without SA modification at 48 h), but also cooperate with BCP to exert synergetic mineralization of calcium phosphate, allowing more osteoblasts to attach, proliferate and differentiate. The more differentiated osteoblasts produced 4.46-fold type I collagen and 2.60-fold osteoprotegerin compared to the control group. Besides, the disassembled nanorods released chitosan oligosaccharide-based micelles, revealing a cartilage-protective effect by reducing the loss of glycosaminoglycan. All these improvements contributed to the light inflammatory response and reduced destruction on cartilage/bone. The findings provide a novel strategy for RA therapy via nanometer-scale dimension mimicking the natural tissues.
32094158 Antibody-mediated inhibition of syndecan-4 dimerisation reduces interleukin (IL)-1 recepto 2020 Apr OBJECTIVE: Syndecan-4 (sdc4) is a cell-anchored proteoglycan that consists of a transmembrane core protein and glucosaminoglycan (GAG) side chains. Binding of soluble factors to the GAG chains of sdc4 may result in the dimerisation of sdc4 and the initiation of downstream signalling cascades. However, the question of how sdc4 dimerisation and signalling affects the response of cells to inflammatory stimuli is unknown. METHODS: Sdc4 immunostaining was performed on rheumatoid arthritis (RA) tissue sections. Interleukin (IL)-1 induced extracellular signal-regulated kinases (ERK) phosphorylation and matrix metalloproteinase-3 production was investigated. Il-1 binding to sdc4 was investigated using immunoprecipitation. IL-1 receptor (IL1R1) staining on wild-type, sdc4 and IL1R1 knockout fibroblasts was performed in fluorescence-activated cell sorting analyses. A blocking sdc4 antibody was used to investigate sdc4 dimerisation, IL1R1 expression and the histological paw destruction in the human tumour necrosis factor-alpha transgenic mouse. RESULTS: We show that in fibroblasts, the loss of sdc4 or the antibody-mediated inhibition of sdc4 dimerisation reduces the cell surface expression of the IL-1R and regulates the sensitivity of fibroblasts to IL-1. We demonstrate that IL-1 directly binds to sdc4 and in an IL-1R-independent manner leads to its dimerisation. IL-1-induced dimerisation of sdc4 regulates caveolin vesicle-mediated trafficking of the IL1R1, which in turn determines the responsiveness to IL-1. Administration of antibodies (Ab) against the dimerisation domain of sdc4, thus, strongly reduces the expression IL1R1 on arthritic fibroblasts both in vitro and an animal model of human RA. CONCLUSION: Collectively, our data suggest that Ab that specifically inhibit sdc4 dimerisation may support anti-IL-1 strategies in diseases such as inflammatory arthritis.
32147565 Important determinants of the patient choice between TNF- vs. non-TNF Biologic disease-mod 2020 Jul OBJECTIVE: To assess why patients choose TNF- versus non-TNF biologics for treating active rheumatoid arthritis (RA) after methotrexate-failure. METHODS: Participants responded to the question "What sort of things help a patient decide the treatment choice between the two types of injectable biologics, TNF biologic versus non-TNF biologic, for treating active rheumatoid arthritis when methotrexate fails to control RA disease activity?" They nominated responses, discussed and then voted. RESULTS: Forty-four patients participated in 10 nominal groups (Birmingham; n=6; New York City: n=4), who were predominantly female (86%), 68% white, with a mean age of 65 (standard deviation [SD], 12) years. Present/past DMARDs included methotrexate in 91%, glucocorticoids in 11%, and biologics and/or Jak-inhibitors in 68% of participants. Pain and fatigue were mild-moderate with means of 3.9 (SD, 2.5) and 4.3 (SD, 2.5), respectively, on 0-10 scale; mean morning joint stiffness was 1.3hours (SD, 2.1). The number of groups that nominated each response and total votes were as follows: (1) Side effects/fear of side effects: 10/10; 31% votes (82/264); (2) Efficacy/ability to reduce joint damage: 9/10; 30% votes (80/264); (3) Doctor's opinion, 6/10; 12% votes (32/264); (4) Cost, 7/10; 9% votes (25/264); (5) Other drugs/comorbidity, 4/10; 12% votes (31/264); (6) Experience of others/information-seeking/own research, 2/10; 2% votes (5/264); (7) Newness, 1/10; 2% votes (6/264); and (8) Convenience/frequency of use, 1/10; 1% votes (3/264). CONCLUSIONS: We identified the patient perspective of choice between TNF versus non-TNF biologic for treating active RA. This knowledge can help in informative shared decision-making in clinical care.
32928503 Effectiveness of a self-management program for joint protection and physical activity in p 2021 Apr BACKGROUND: Rheumatoid arthritis is a chronic, systemic disease, which results in progressive destruction of the joints and a reduction in quality of life. Joint protection can minimize injuries that worsen arthritis and pain and certain activities can help patients control or reduce the symptoms of this chronic disease. OBJECTIVES: To determine the effectiveness of a self-management program for joint protection and physical activity for patients with rheumatoid arthritis based on self-efficacy theory. DESIGN: A two-arm (experimental vs control) randomized trial. PARTICIPANTS: Adult patients with rheumatoid arthritis were recruited from rheumatology departments of a medical center in Northern Taiwan. A total of 224 patients met the inclusion criteria and agreed to participate in the study. METHODS: Eligible participants with rheumatoid arthritis were randomly assigned to either an 8-week program in self-management of joint protection and physical activity with nursing support (intervention group, n = 112) or standard care for rheumatology (control group, n = 112). Outcome variables were assessed at baseline and 2-, 3-, and 6-months after commencement of the intervention, which included measures of disease activity, and self-assessments for self-efficacy, quality of life, and self-management behaviors. Differences in outcome variables over time between the groups were analyzed with generalized estimating equations; the level of significance was set at p < 05. RESULTS: The mean age of participants was 58.8 years, duration of the rheumatoid arthritis was 10 years, and most participants (86%) were female. Characteristics and assessment variables did not differ between the two groups at baseline. When compared with the control group at 6 months following initiation of the self-management program, participants in the intervention group demonstrated significantly greater improvement in physical functioning (B = 4.08, p < 05), self-efficacy of pain (B = 4.89, p < .05), and self-management behaviors (B = 4.65, p < 05). CONCLUSIONS: A self-management program based on self-efficacy theory that focused on joint protection and physical activities resulted in significant improvements in physical functioning, self-efficacy, and self-management behaviors 6 months following commencement of the intervention. Nurses provided individualized evaluations and support, which may have made it easier for participants to learn and perform the activities. After commencement of participation in the intervention, no improvements were seen until 6 months of participation. This delay may suggest patients with chronic disease may need a longer duration of self-management training and increased follow-up time to incorporate lifestyle changes. Future studies measuring long-term outcomes are suggested.
32965587 Utility of the neutrophil-to-lymphocyte ratio for predicting bacterial infection in patien 2020 Dec This study aimed to describe the utility of the neutrophil-to-lymphocyte ratio (NLR) for predicting bacterial infections in patients with rheumatoid arthritis (RA) treated with Tocilizumab (TCZ). We extracted RA patients treated with TCZ in whom an infection developed between April 2008 and March 2018 from our hospital database. We divided these patients into the bacterial infection and non-bacterial infection groups and compared their background, C-reactive protein (CRP) values, white blood cell count (WBC), the NLR at the time of infection diagnosis, and the ratio of the NLR at the time of infection diagnosis (post-NLR) to the NLR at baseline (pre-NLR). Of the 196 patients who received TCZ, 21 experienced a bacterial infection and 20 had a non-bacterial infection. The median CRP level, WBC count, post-NLR, and post-NLR/pre-NLR ratio in the bacterial infection group were significantly higher than in the non-bacterial infection group. In receiver operating characteristics (ROC) curve analysis for predicting bacterial infection, the area under the curve (AUC) for CRP, WBC, NLR, and the post-NLR/pre-NLR ratio were 0.787, 0.857, 0.887, and 0.975, respectively. The cut-off value of 2.25 for the post-NLR/pre-NLR ratio showed the greatest sensitivity (90.5%) and specificity (100%). The post-NLR/pre-NLR ratio may be a useful surrogate marker for predicting bacterial infections in patients with RA treated with TCZ.
31745566 Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted di 2020 Aug 1 OBJECTIVES: The effectiveness of TNF inhibitors in RA has been shown to be affected by obesity. No such effect has been found for abatacept and rituximab, while for tocilizumab results are ambiguous. Additionally, it remains unresolved whether sex is an effect modifier for obesity. We investigated the impact of obesity on the drug effectiveness of conventional synthetic or biologic DMARDs, taking into account potential sex-specific differences. METHODS: Data from 10 593 RA patients included in the German observational cohort study Rheumatoid Arthritis: oBservation of BIologic Therapy (RABBIT) since 2009 were analysed. Patients had to have a BMI ≥18.5 kg/m2, at least one follow-up and 6 months of observation time. The influence of obesity on drug effectiveness was investigated by regression analysis, adjusting for potential confounders. RESULTS: Obesity had a negative impact on improvement in the DAS with 28 joints using ESR as an inflammation marker of -0.15 (95% CI: -0.26; -0.04) units for women receiving conventional synthetic DMARDs, -0.22 (95% CI: -0.31; -0.12) units for women receiving TNF inhibitors, -0.22 (95% CI: -0.42; -0.03) units for women receiving tocilizumab and -0.41 (95% CI: -0.74; -0.07) units for men receiving tocilizumab. Overall, no negative obesity effects on the effectiveness of rituximab and abatacept were found. CONCLUSION: Obesity has a negative impact on the effectiveness of cytokine-targeted but not cell-targeted therapies in daily practice, affecting more outcomes and therapies in women than in men. Overall, no effects of obesity on treatment effectiveness were found for rituximab and abatacept.
31057111 Antinuclear Antibodies and Lupus-like Manifestations in Rheumatoid Arthritis and Ankylosin 2020 BACKGROUND: Up to 44% of patients treated with infliximab and 7% of patients treated with etanercept reported to have anti-drug antibodies within the first 6 months of treatment. Recently, anti-TNF-α therapies have been reported to be employed in the induction of the druginduced lupus erythematous. OBJECTIVE: The aim of the present study was to investigate the relationship between anti-TNFα antibodies and various manifestations of lupus erythematous. METHODS: We enrolled a total of 56 cases divided into 28 known cases of rheumatoid arthritis and 28 cases of ankylosing spondylitis patients and 56 controls. The case group was divided into 4 groups according to the underlying disease (RA or AS) and treatment regimen (infliximab or etanercept). ANA and anti-dsDNA levels and lupus criteria were assessed at the beginning of the study and 4 months after the initiation of anti-TNFα. RESULTS: 36% and 21% of RA patients treated with infliximab, were ANA and anti-dsDNA positive after 4 months (P=0.003, P=0.025). 28% and 7% of RA patients treated with etanercept, were ANA and anti-dsDNA positive after 4 months (P=0.009, P=0.15). 21% and 7% of AS patients treated with infliximab, were ANA and anti-dsDNA positive, respectively (P=0.025, P=0.15). 14% and 7% of AS patients treated with etanercept, were ANA and anti-dsDNA positive, respectively (P=0.63, P=0.15). Three patients who were positive for auto-antibodies developed three criteria for SLE. CONCLUSION: Infliximab potentially may increase both ANA and anti-dsDNA levels in rheumatoid arthritis, but only ANA in ankylosing spondylitis patients. In general, clinicians should consider different clinical symptoms of ATIL, which may be present as a lupus-like syndrome similar to idiopathic SLE or classical DIL.
32779338 Impact of biological treatment on left ventricular dysfunction determined by global circum 2020 Oct AIM: To evaluate left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA) and to determine the impact of biological treatment on LV function in these patients using global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) values assessed by feature tracking cardiac magnetic resonance (FT-CMR) imaging. METHODS: Eighty patients with RA and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Patients with RA received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Global strains were calculated in 16 LV segments. RESULTS: No significant differences in cardiovascular risk factors were found between the RA group and controls. GCS was 21% lower in the RA group compared with controls (P < 0.001) and was 14% lower in the csDMARDs group compared with the bDMARDs group (P = 0.002), whereas, there was no significant difference in GLS and GRS between the RA group and the controls. In regard to strain rates, diastolic GCS and GRS rates were significantly lower in the RA group (P < 0.001, 0.011, respectively). In univariate analyses, GCS was significantly associated with the Simplified Disease Activity Index, bDMARDs, swollen joint count, anti-cyclic citrullinated peptides antibodies and matrix metalloproteinase-3, but in multivariable analysis, only bDMARDs was significantly associated with GCS (P = 0.021). CONCLUSION: Global circumferential strain, GLS and GRS assessed by FT-CMR can reveal subclinical LV dysfunction in patients with RA. Furthermore, they can be used to determine the normalization of LV regional dysfunction induced by bDMARDs possibly related to disease activity reduction.
30877214 Evaluation of the Implementation of Guidelines on the Treatment of Osteoporosis in Patient 2020 Jan OBJECTIVE: To assess whether the 2003 and 2014 French guidelines on the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) and the 2012 update of the French guidelines for the treatment of postmenopausal osteoporosis (PMOP) were applied in patients with rheumatoid arthritis (RA). METHODS: We conducted a cross-sectional study of 776 patients with RA (19 centers). We collected the data required for the application of the various recommendations (age, sex, prednisone intake, low-energy fracture, history in the immediate family of hip fractures, and bone densitometry), anti-osteoporotic drugs, and the various factors that may be associated with the application of the recommendations. RESULTS: Of the patients who should have received antiosteoporosis treatment, there were 22.6% actually treated (according to the 2014 guidelines), 27.3% actually treated according to the 2003 guidelines, and of postmenopausal women, 23.6% (according to the 2012 PMOP guidelines). Applying the 2014 GIOP guidelines increased the theoretical number of patients requiring treatment relative to the 2003 GIOP guidelines (77% vs 53%; p < 0.001). In multivariate analysis, being treated was associated with a spinal T score ≤ -2 SD according to the 2014 guidelines; with not taking part in physical activity for more than 30 min a day according to the 2003 guidelines; and with older age, lower body mass index, and a T score ≤ -2.5 SD in at least 1 site according to the PMOP guidelines. CONCLUSION: Patients with RA had inadequate prevention of GIOP and PMOP. The management of osteoporosis needs to be improved in this population.
31280937 Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional 2020 Feb OBJECTIVES: To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). METHODS: Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan-Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. RESULTS: 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. CONCLUSION: In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.
31377797 Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheum 2020 Feb 1 OBJECTIVE: To examine the role of Tie2 signalling in macrophage activation within the context of the inflammatory synovial microenvironment present in patients with RA and PsA. METHODS: Clinical responses and macrophage function were examined in wild-type and Tie2-overexpressing (Tie2-TG) mice in the K/BxN serum transfer model of arthritis. Macrophages derived from peripheral blood monocytes from healthy donors, RA and PsA patients, and RA and PsA synovial tissue explants were stimulated with TNF (10 ng/ml), angiopoietin (Ang)-1 or Ang-2 (200 ng/ml), or incubated with an anti-Ang2 neutralizing antibody. mRNA and protein expression of inflammatory mediators was analysed by quantitative PCR, ELISA and Luminex. RESULTS: Tie2-TG mice displayed more clinically severe arthritis than wild-type mice, accompanied by enhanced joint expression of IL6, IL12B, NOS2, CCL2 and CXCL10, and activation of bone marrow-derived macrophages in response to Ang-2 stimulation. Ang-1 and Ang-2 significantly enhanced TNF-induced expression of pro-inflammatory cytokines and chemokines in macrophages from healthy donors differentiated with RA and PsA SF and peripheral blood-derived macrophages from RA and PsA patients. Both Ang-1 and Ang-2 induced the production of IL-6, IL-12p40, IL-8 and CCL-3 in synovial tissue explants of RA and PsA patients, and Ang-2 neutralization suppressed the production of IL-6 and IL-8 in the synovial tissue of RA patients. CONCLUSION: Tie2 signalling enhances TNF-dependent activation of macrophages within the context of ongoing synovial inflammation in RA and PsA, and neutralization of Tie2 ligands might be a promising therapeutic target in the treatment of these diseases.