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ID PMID Title PublicationDate abstract
31763680 IL-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility. 2020 Jan 31 Interleukin-21 (IL-21) is a cytokine that plays a crucial role in pathogenesis and activity of the rheumatoid arthritis (RA). Meanwhile, genetic polymorphisms in the IL-21 gene may alter its expression. Previous studies have reported conflicting results assessing the association between the IL-21 rs6822844 G/T polymorphism and RA risk. Thus, it's necessary to perform a meta-analysis to definite above relationship. PubMed database was searched for all papers published until October 20, 2019. Nine case-control studies with 9998 cases and 10742 controls were retrieved based on the search criteria at last. Odds ratio (95% confidence interval) was used to calculate the strength of this association. Publication bias was detected using both Begg's and Egger's tests. Overall, the IL-21 rs6822844 G/T polymorphism was found to be significantly associated with decreased RA risk (e.g. T-allele versus G-allele: OR = 0.81, 95% CI = 0.72-0.91, P < 0.001). In addition, decreased RA risk was also detected both in Asians (eg: TT+TG versus GG: OR = 0.42, 95% CI = 0.31-0.56, P < 0.001) and Caucasians (eg: TT+TG versus GG: OR = 0.85, 95% CI = 0.80-0.91, P < 0.001). A similar trend in association was found in the source of the control and genotype method subgroups. Furthermore, subgroup analysis of rheumatoid factor status revealed a protective relationship between the IL-21 rs6822844 G/T polymorphism and RF+/RF- RA risk. A similar relationship was noted in the anti-citrullinated protein antibody status subgroup. The results of the present study suggest that the IL-21 rs6822844 G/T polymorphism was significantly associated with decreased RA susceptibility.
31365331 Depression, disability and sleep disturbance are the main explanatory factors of fatigue i 2020 Mar OBJECTIVES: Fatigue is one of the most prevalent and disabling symptoms among patients with rheumatoid arthritis (RA), however, it is frequently neglected by health professionals. This study aimed to develop a multidimensional explanatory model of fatigue in patients with RA as a basis for better understanding and intervention. METHODS: This was an ancillary analysis of an observational, cross-sectional, single centre study. Patients completed a questionnaire including demographic data and measures of pain, sleep, disability, anxiety, depression, and personality. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). Disease activity and haemoglobin levels were assessed. Path analysis was performed to test and improve a hypothesised model for fatigue. RESULTS: This analysis included 142 patients, with a mean (SD) age of 61.1 (11.7) years. The final path analysis model presented acceptable fit and explained 60.0% of the variance of fatigue. The predominant direct explanatory factors identified were disability (46.5%) and depression (41.2%), the latter having an additional indirect influence of 19% through disability. Age (-16.2%) and sleep disturbance (15.7%) were also directly linked to fatigue. Personality trait extroversion (-22.4%), pain (20.0%), and disease activity (14.9%) are only indirectly related to fatigue. CONCLUSIONS: Depression, disability and sleep disturbance appear to be the main factors explaining fatigue in patients with RA. Disease activity, pain, and personality seem to play only a secondary role, extroversion being the only personality trait associated with fatigue. These findings foster a shift in the paradigm of care towards a more holistic management of fatigue, integrating adjunctive therapies beyond measures targeted solely at disease remission.
32496302 Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheum 2020 Jun 20 BACKGROUND: Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. METHODS: Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. RESULTS: The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013). CONCLUSION: Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.
31267533 Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rh 2020 Feb This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.
31300847 Re-conceptualizing functional status through experiences of young adults with inflammatory 2020 Feb The objective of this study is to assess the impact of inflammatory arthritis on young adults' activity participation using quantitative and qualitative methods to advance the field's conceptualization of functional status. Young adults diagnosed with juvenile idiopathic arthritis or rheumatoid arthritis completed (1) the Health Assessment Questionnaire-Disability Index to determine functional status and (2) the day reconstruction method to explore experiential dimensions of function, including functional performance, functional satisfaction, and severity of arthritis symptoms during activities on the previous day. Bivariate analyses were conducted to examine relationships between functional status, experiential variables, and demographic variables. Open-ended questions were provided for participants to report ways that arthritis affected their participation that were not otherwise reflected within survey questions; responses were numerically coded using summative content analysis. Among 37 participants (24.8 ± 3.3 years old), 70% reported moderate-to-severe disability. On average, participants experienced pain, stiffness, or fatigue for more than 50% of their waking hours. Functional status significantly correlated with functional performance (r = - 0.39, p = 0.02) and satisfaction (r = - 0.39, p = 0.02), yet did not correlate with stiffness or fatigue severity or duration of symptoms throughout the day. Participants described strategies that improved their ability to participate in certain activities but reduced their overall quality of activity engagement and caused emotional distress. Young adults with arthritis may experience more significant functional limitations than previously reported. Traditional measures of functional assessment may not capture experiential components of activity that affect participation, such as severity of stiffness or fatigue or the duration of symptoms throughout the day.
32859051 Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca(2+) Influx in Nk 2020 Aug 26 B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3(-/-)) the spleen's histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3(-/-) mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3(-/-) and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca(2+) signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3(-/-) mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3(-/-) mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3(-/-) mice showed decreased intracellular Ca(2+) signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation.
32102567 Platelets Disseminate Extracellular Vesicles in Lymph in Rheumatoid Arthritis. 2020 Apr OBJECTIVE: The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ(3) and platelet-derived serotonin. CONCLUSIONS: These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
32598046 Regular use of proton pump inhibitor and risk of rheumatoid arthritis in women: a prospect 2020 Aug BACKGROUND: Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA). AIM: To evaluate regular use of PPIs and risk of RA. METHODS: This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2 years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders. RESULTS: We documented 421 cases of RA over 1 753 879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR = 1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend = 0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with >0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for >4 years' use. CONCLUSIONS: Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding.
32358664 Comparison of three ultrasonographic examinations on the synovial membrane vascularity of 2020 Jun Rheumatoid arthritis (RA) is a systemic autoimmune disease involving multiple joints and often involves the small joints, and the lesions are symmetric, invasive, and disabling. Synovial blood flow in patients with RA was compared using color Doppler flow imaging (CDFI), power Doppler ultrasound (PDUS), and superb microvascular imaging (SMI) to determine the application value of SMI in synovial vasospasm of knee joints. The blood flow signals of the suprapatellar recess in the knee joints of 41 RA patients (49 knees) were measured prior to undergoing total knee arthroplasty (TKA), recorded, and graded by CDFI, PDUS, and SMI. The results of the three ultrasound examination methods were compared and analyzed. The SMI grading was compared with the pathologic grade of the synovial membrane. Forty-one patients underwent 49 TKAs. The display rate of the synovial blood flow signal was 93.9% in the CDFI model, 97.9% in the PDUS model, and 100% in the SMI model. There were statistically significant differences in the results between the three ultrasound examination methods (H(C) = 11.84, P < 0.05). The consistency of the SMI and pathologic grades of synovial membranes was better than the other methods (kappa = 0.639, P < 0.05). Compared with CDFI and PDUS, the signal of synovia flow detected by SMI was significantly higher in RA patients. SMI classification had a better consistency with the pathologic grade, and SMI has application value in assessing the activity of RA.
32025884 Disease activity, morning stiffness and missing teeth are associated with oral health-rela 2020 Oct OBJECTIVES: The aim of this cross-sectional study was to assess oral health-related quality of life (OHRQoL) in patients with rheumatoid arthritis (RA) and its relation to specific RA characteristics. MATERIAL AND METHODS: Within the oral examination, the need for dental (carious teeth showing cavitation) and periodontal treatment (presence of a probing depth ≥ 3.5 mm) and the number of missing teeth (M-T) were recorded. OHRQoL was assessed with the German short version of the Oral Health Impact Profile (OHIP G14). The disease activity score (DAS28-ESR), disease duration, number of swollen/painful joints and duration of morning stiffness were retrieved from the patient records. RESULTS: A total of 176 patients with a mean age of 62.5 ± 10.2 years were included. The overall OHIP G14 sum score was 5.4 ± 7.1. The M-T showed a significant correlation with the dimensions of oral function (r = 0.25, p = 0.001) and psychosocial impact (r = 0.20, p = 0.009) and the sum score (r = 0.26, p = 0.001). The DAS28-ESR showed a significant correlation with psychosocial impact (r = 0.19, p = 0.012) and the sum score (r = 0.16, p = 0.041). The duration of morning stiffness was correlated with oral function (r = 0.19, p = 0.019), psychosocial impact (r = 0.18, p = 0.024) and the sum score (r = 0.22, p = 0.006). The effect size of these correlations was interpreted as small. CONCLUSION: Disease activity, morning stiffness and missing teeth are associated to OHRQoL of patients with RA. Accordingly, multidisciplinary dental care appears necessary for these patients. CLINICAL RELEVANCE: The prevention of tooth loss as well as the consideration of psychosocial and disease-specific parameters in the multidisciplinary dental care of RA patients is necessary.
31742641 Association between depression and rheumatoid arthritis: two longitudinal follow-up studie 2020 Aug 1 OBJECTIVE: To investigate the bidirectional relation between RA and depression. METHODS: Data from the Korean Health Insurance Review and Assessment Service - National Sample Cohort from 2002 to 2013 were analysed. Patients ≥20 years of age were included. Study I was conducted with 38 087 depression patients and 152 348 matched control participants. Study II was conducted with 7385 RA patients and 29 540 matched control participants. Stratified Cox proportional hazards models were used to analyse the hazard ratios (HRs) for depression and RA (study I) and for RA and depression (study II). The data were adjusted by the Charlson comorbidity index; rheumatic disease was excluded. Subgroups were also analysed according to age and sex. RESULTS: A total of 0.7% (1260/38 087) of the depression group and 0.6% (883/152 348) of the control I group had RA (P = 0.02). The HR for RA in the depression group was not significantly higher than that in control I group. In study II, 5.5% (408/7385) of the RA group and 4.3% (1246/29 540) of the control II group presented with depression (P < 0.001). The RA patients showed an adjusted depression HR that was 1.20 times higher (95% CI 1.07, 1.34; P = 0.002) than that of the control group. The >30-years-old and women subgroups of RA patients showed higher depression HRs than the control subgroups. CONCLUSION: RA increased the risk of depression; however, depression did not increase the risk of RA in the Korean adult population.
32209540 Immunosuppression and the risk of readmission and mortality in patients with rheumatoid ar 2020 May OBJECTIVES: The impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries. METHODS: This retrospective cohort study used Medicare data 2006-2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes. RESULTS: We identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5-10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category. CONCLUSIONS: Recent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.
32438375 Cannabis-based medicinal products in arthritis, a painful conundrum. 2020 May 22 AIMS: The changing medicolegal climate regarding the medicinal use of cannabinoids in New Zealand will increase the likelihood of patients consulting general practitioners (GPs) about these products. Arthritis is a common medical condition for which cannabis-based products are promoted and used; however, doctors' knowledge about the efficacy and safety of these products in the setting of arthritis may be limited. METHODS: We undertook a rapid review of the medical literature on cannabis-based medicinal products in arthritis. RESULTS: Animal studies have identified endocannabinoid pathways in arthritis that are potentially amenable to interventions. One randomised placebo-controlled trial of Sativex® in adults with rheumatoid arthritis has shown some improvements in pain but not in comparison with a standardised pharmacological treatment regimen. Systematic reviews of cannabis-based products in arthritis have determined that there is currently insufficient evidence to recommend cannabis-based medicines for routine clinical use. There were five ongoing registered clinical trials of cannabis-based products in arthritis, the results of which are yet to be reported. CONCLUSIONS: While animal models have identified possible endocannabinoid pathways in arthritis, there is no clear evidence of benefit in humans or comparative efficacy with current treatments. At this stage, there is little evidence to support GPs prescribing cannabis-based medicinal products for arthritis.
33086882 Cost-utility analysis of the anti-TNF therapy for rheumatoid arthritis in a real-world bas 2021 Oct BACKGROUND: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil. METHODS: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. RESULTS: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses. CONCLUSION: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them.
32653504 Targeting interleukin-4 to the arthritic joint. 2020 Oct 10 Anti-inflammatory cytokines are a promising class of therapeutics for treatment of rheumatoid arthritis (RA), but their use is currently limited by a rapid clearance and systemic toxicity. Interleukin-4 is a small cytokine with potential for RA therapy. To increase its pharmacokinetic features, we engineered a murine IL4 conjugate by incorporating an unnatural amino acid through genetic code expansion to which PEG-folate, as a targeting moiety and PEG alone as control, were site-specifically bound. Both IL4 conjugates retained bioactivity and induced primary murine macrophage polarization into an alternatively activated (M2) related phenotype. The PEGylated conjugates had a terminal half-life of about four hours in healthy mice compared to unPEGylated IL4 (0.76 h). We showed that both conjugates successfully accumulated into arthritic joints in an antigen-induced arthritis (AIA) mouse model, as assessed by non-invasive fluorescence imaging. The modular nature of the IL4 conjugate chemistry presented herein facilitates easy adaption of PEG chain length and targeting moieties for further improvement of half-life and targeting function for future efficacy studies.
32319221 Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary 2020 Sep OBJECTIVE: To evaluate whether biologic disease-modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression. METHODS: In this single-center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low-attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham-D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: After adjustment for the segment stenosis score, the Framingham-D'Agostino score, and time-varying Disease Activity Score in 28 joints using the C-reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long-term CVD risk (OR 0.15 [95% CI 0.04-0.60]). Noncalcified and low-attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low-attenuation plaque at baseline (OR 0.21 [95% CI 0.04-0.99] and OR 0.08 [95% CI 0.01-0.70], respectively), but not in those without noncalcified or low-attenuation plaque. Per-segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05-15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17-0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low-attenuation plaque loss (P = 0.042). CONCLUSION: Our findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis.
31969215 Safety of surgery in patients with rheumatoid arthritis treated with tocilizumab: data fro 2020 May OBJECTIVES: To investigate the frequency and risk factors of postoperative complications in RA patients treated with tocilizumab (TCZ). METHODS: The French registry REGATE recruited 1496 RA patients receiving TCZ in routine care. Data from patients treated with TCZ who underwent surgery were reviewed. Frequency of post-surgery complications was collected and compared in patients with and without complications in order to identify factors associated with complications. Similar analysis was performed in patients with postoperative infection. RESULTS: We identified 167 patients who underwent 175 surgical procedures including 103 orthopaedic surgeries (58.9%). The patients were mainly women (84%) with a mean disease duration of 14.96±11.29 years. The mean delay between surgery and the last TCZ infusion was 4.94±1.74 weeks. Fifteen patients experienced 15 complications (8.6%) with 10 severe infections including 5 surgical site infections (33.3%). There was no significant difference between patients with and without complications. In multivariate analysis, previous treatment with rituximab in the previous year tended to be associated with postoperative complications (OR: 3.27, IC95% 0.92-11.49, p=0.06). Concerning postoperative infections, diabetes mellitus tended to be associated with this complication (OR: 3.73, IC95% 0.88-15.79, p=0.06) in multivariate analysis. CONCLUSIONS: In RA patients treated with TCZ in perfusion, the rate of surgical complications was low: 8.6%. The median time between surgery and last infusion was relatively short according to half-life of TCZ but did not influence the rate of postoperative complications.
32219519 [Janus kinase inhibitors : State of the art in clinical use and future perspectives]. 2020 Apr BACKGROUND: Cytokines and associated intracellular signal cascades play a major role in the pathogenesis of autoimmune diseases. Janus kinases (JAK) are part of these intracellular signal transduction processes. A relatively new drug group of targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) are JAK inhibitors (JAKi) and are a promising treatment approach for autoimmune diseases. EFFICACY: Hitherto, three JAKis, Tofacitinib, Baricitinib and Upadacitinib, have been approved for treatment of Rheumatoid Arthritis (RA) in the USA, Switzerland and the EU. Filgotinib, another JAKi, also showed promising results in the treatment of RA. Furthermore, tofacitinib received approval for the treatment of ulcerative colitis and psoriatic arthritis. In addition to the JAKis already mentioned, several other JAKis, e.g. filgotinib and peficitinib, are being and were investigated in various studies on indications, such as atopic dermatitis, ankylosing spondylitis and systemic lupus erythematosus. SAFETY: Being immunosuppressants, JAKis show an elevated incidence of severe infections, comparable to biologics. The increased reactivation of varicella zoster virus is especially noteworthy. Under JAKi treatment cytopenia is also more frequent. Lymphopenia under JAKi treatment is of particular clinical relevance because of its association with an increase in the number of severe infections. Furthermore, an elevated risk of thromboembolic events, particularly pulmonary embolism has been noted. The risks concerning metabolic alterations and the occurrence of malignant neoplasms are comparable to those under treatment with biologics.
31474600 Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Val 2020 Jun 1 OBJECTIVE: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings. METHODS: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score. RESULTS: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively. CONCLUSION: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).
33307515 Association of IL-35 expression and gene polymorphisms in rheumatoid arthritis. 2021 Jan Interleukin (IL)-35 is the newest member of the IL-12 family. It is expressed in many immune cells and has been recognized as a novel inflammatory cytokine that may have bifunctional properties. Recent findings have indicated that the expression of IL-35 is abnormal in rheumatoid arthritis (RA) patients. However, the results were inconsistent. In this study, 400 RA patients were recruited to evaluate serum levels of IL-35 in a Chinese Han population by enzyme-linked immunosorbent assay. The association of IL-35 gene polymorphisms and RA genetic susceptibility was investigated in 400 RA patients and 612 healthy controls. The results showed that serum levels of IL-35 were elevated in 100 RA patients compared to 51 healthy controls, relating to disease activity and synovial fluid IL-35 expression in the training cohort. Another independent 300 RA patients and 369 other rheumatic disease patients (98 lupus, 95 osteoarthritis, 95 gout, 42 Sjogren's syndrome and 39 ankylosing spondylitis patients) confirmed that serum levels of IL-35 were elevated in RA patients, and serum IL-35 has good diagnostic ability for differentiating RA from the other rheumatic diseases. The genotyping of 10 IL-35 polymorphisms, including rs2227314, rs2243115, rs2243123, rs2243131, rs568408, rs583911, rs428253, rs4740, rs9807813 and rs4905, revealed that rs2227314, rs2243131, rs9807813, and rs583911 were correlated with RA risk. Different genotypes (rs2227314, rs583911, and rs9807813) exhibited different expression of IL-35. These findings demonstrate that serum levels of IL-35 are increased in RA patients and that IL-35 polymorphisms are correlated with RA risk.