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33210598 [Inflammation caused by different immune cell subsets is involved in bone destruction of r 2020 Nov Objective To observe the relationship of rheumatoid arthritis (RA) bone destruction with T cells, regulatory T cells (Tregs), CD19(+) B cells and immune inflammation. Methods The study enrolled randomly 20 RA patients (RA group) and 20 normal controls (NC group). Bone mineral density was measured by DXEA dual energy X-ray bone densitometer. The serum levels of γ-interferon (IFN-γ) of Th1 cells, interleukin-4 (IL-4) of Th2 cells, IL-17, type I procollagen amino terminal propeptide (PINP), type I collagen carboxy terminal peptide (CTx), receptor activator of NF-κB ligand (RANKL) and osteoprotectin (OPG) were detected by ELISA. T-cell subsets, Tregs, CD19(+) B cells in peripheral blood were measured by flow cytometry. Spearman method was used to analyze the correlations of T cells, Treg and CD19(+) B cells with bone density and Th1 and Th2 cytokines. Results The bone mineral density T value of the RA group was lower than that of the NC group. The bone mineral density T value of the double forearm was lower than that of the lumbar spine in the RA group. Compared with the NC group, the expression of IFN-γ, IL-17, Th1/Th2 cells, CTx, RANKL increased, and IL-4, PINP decreased in the RA group. Compared with the NC group, the expression of CD4(+)/CD8(+) T cells, CD19(+) B cells increased, and CD8(+) T cells, CD4(+)CD25(+) Tregs decreased in the RA group. Correlation analysis showed that CD8(+) T cells were positively correlated with Th1/Th2 cells and IL-17, while CD4(+) CD25(+) Tregs were negatively correlated with CTx, and CD19(+) B cells were negatively correlated with OPG in RA. Conclusion T cells and CD19(+) B cells may participate in the process of bone destruction in RA by mediating inflammatory immunity.
31729947 The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Admin 2020 BACKGROUND: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of β-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed. OBJECTIVES: This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA. METHODS: Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed. RESULTS: The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients. CONCLUSION: Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.
31813561 Risk of exacerbation of pulmonary comorbidities in patients with rheumatoid arthritis afte 2020 Jun BACKGROUND: Biologic agents may pose a potential risk for exacerbations of pulmonary comorbidities in rheumatoid arthritis (RA) patients. METHODS: Using U.S. Medicare and Truven MarketScan databases, we identified three cohorts of RA patients with interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), or asthma who initiated abatacept or a TNF inhibitor (TNFi). The primary outcome was a composite exacerbation of individual pulmonary comorbidities based on inpatient or emergency department (ED) visits due to exacerbation of the given pulmonary comorbidity. To adjust for >60 baseline confounders, we used propensity-score fine stratification (PSS) and weighting. Negative binomial regression model estimated a cohort-specific incidence rate ratio (IRR) and 95% confidence interval (CI) of the primary outcome per database, comparing abatacept versus TNFi. Database-specific IRRs were combined using a random-effects meta-analysis. RESULTS: We identified 3,295 ILD, 7,161 COPD, and 5,613 asthma patients with RA who initiated either abatacept or a TNFi. IR of composite exacerbation was high in all three pulmonary cohorts but highest in COPD cohort (3.59-11.80 per 100 person-years in ILD, 20.68-34.97 in COPD, and 4.66-13.78 in asthma). After PSS weighting, the combined IRR (95%CI) in abatacept initiators versus TNFi initiators was 0.44 (0.18-1.09) for ILD exacerbation, 0.91 (0.80-1.03) for COPD exacerbation, and 0.81 (0.54-1.22) for asthma exacerbation. CONCLUSION: Among patients with RA and pulmonary comorbidities, exacerbations requiring inpatient or ED visits occurred frequently after initiating abatacept or TNFi. Overall, we found no significant difference in the risk of ILD, COPD or asthma exacerbation between abatacept and TNFi initiators, but precision of our estimates is limited.
33679725 Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Bio 2020 Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.
31732558 Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with 2020 Aug 1 OBJECTIVE: To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT00908089). RESULTS: There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%). CONCLUSION: Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.
31263067 Toward Defining Primary and Secondary Nonresponse in Rheumatoid Arthritis Patients Treated 2020 Apr OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS: Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.
32808557 Real-world observational study of biosimilars in inflammatory arthritis treatment: a syste 2021 Jan INTRODUCTION: The use of biological agents in patients with rheumatic diseases has achieved the therapeutic target, i.e., remission or low disease activity. The share of biological agents has been growing with the approval of biosimilars, which have been recognized for their equivalent efficacy, safety, pharmacokinetics, and immunogenicity to the original as well as their reduced economic burden. AREA COVERED: Biosimilars are being examined for their bioequivalence to reference products in randomized-controlled trials; however, the use of biosimilars in actual clinical practice is complicated owing to issues with switching and comorbidities. Therefore, this review describes real-world data in the rapidly evolving field of biosimilars in the treatment of rheumatoid arthritis and spondyloarthropathy, including ankylosing spondylitis and psoriatic arthritis. EXPERT OPINION: According to published data, the use of biosimilars for inflammatory arthritis led to no significant inferiority in treatment outcomes and resulted in considerable cost savings in the real-world. Currently, beyond the use of biosimilars, issues with the interchangeability of biosimilars, including immunogenicity, should be addressed. Strategies to overcome these concerns will improve treatment efficacy and safety in patients with inflammatory arthritis.
32014877 Depression: a common comorbidity in women with rheumatoid arthritis-results from an Austri 2020 Feb 2 OBJECTIVES: Previous research showed that depression is common in rheumatoid arthritis (RA). However, the prevalence very much depends on different assessment tools and sociocultural differences, respectively. The main study aim and research question was to investigate the proportion of depressive symptoms in Austrian female patients with RA. SETTING: A nationwide multicentre study with seven secondary care centres all over Austria (hospital-based rheumatological outpatient clinics and private practices). PARTICIPANTS: 319 patients with RA and 306 healthy controls (HCO), all female Caucasians, were asked to complete a Beck's Depression Inventory-Fast Screen (BDI-FS). Patients and HCO were ≥18 years. Patients had to fulfil the 2010 classification criteria for RA. In addition, disease activity, disability, medication, drinking of alcoholic beverages, smoking and occupational status were evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: A BDI-FS cut-off value of ≥4, per definition, indicates the presence of a depressive symptomatology. RESULTS: The return rate of questionnaires was high: 235/319 (73.7%) in patients with RA and 180/306 (58.8%), ending up with 392 complete questionnaires from 223 patients with RA (69.9%) and 169 HCO (55.2%). The BDI-FS was significantly higher in patients with RA (median BDI-FS 2 (IQR 0-4) vs median 1 (IQR 0-2) in HCO, p<0.001). BDI-FS scores from ≥4, which by definition indicate depression, were found in 29.6% of patients with RA and 12.4% of HCO (p<0.001). Depressive symptoms were strongly associated with disease activity (Clinical Disease Activity Index, p<0.001) and disability (Health Assessment Questionnaire, p<0.005). No association of depressive symptoms with age, alcohol consumption, smoking, occupational status or use of medication was found. CONCLUSIONS: One-third of female patients with RA showed depressive symptoms. Depression was significantly higher in female patients with RA than in female HCO and was strongly associated with disease activity and disability. It would be of interest to address the same question in male participants.
32594150 TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independe 2020 Nov 1 OBJECTIVE: RA is an autoimmune inflammatory joint disease. Both RF and ACPA are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28. METHODS: Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 h before measuring IL-6, TNFα and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28. RESULTS: RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28. CONCLUSIONS: Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.
32075453 A budget impact analysis for making treatment decisions based on anti-cyclic citrullinated 2020 Jun Aim: Given that rheumatoid arthritis (RA) patients with high anti-citrullinated protein antibodies (ACPA) titer values respond well to abatacept, the aim of this study was to estimate the annual budget impact of anti-cyclic citrullinated peptide (anti-CCP) testing and treatment selection based on anti-CCP test results.Materials and methods: Budget impact analysis was conducted for patients with moderate-to-severe RA on biologic or Janus kinase inhibitor (JAKi) treatment from a hypothetical US commercial payer perspective. The following market scenarios were compared: (1) 90% of target patients receive anti-CCP testing and the results of anti-CCP testing do not impact the treatment selection; (2) 100% of target patients receive anti-CCP testing and the results of anti-CCP testing have an impact on treatment selection such that an increased proportion of patients with high titer of ACPA receive abatacept. A hypothetical assumption was made that the use of abatacept would be increased by 2% in Scenario 2 versus 1. Scenario analyses were conducted by varying the target population and rebate rates.Results: In a hypothetical health plan with one million insured adults, 2,181 patients would be on a biologic or JAKi treatment for moderate-to-severe RA. In Scenario 1, the anti-CCP test cost was $186,155 and annual treatment cost was $101,854,295, totaling to $102,040,450. In Scenario 2, the anti-CCP test cost increased by $20,684 and treatment cost increased by $160,467, totaling an overall budget increase of $181,151. This was equivalent to a per member per month (PMPM) increase of $0.015. The budget impact results were consistently negligible across the scenario analyses.Limitations: The analysis only considered testing and medication costs. Some parameters used in the analysis, such as the rebate rates, are not generalizable and health plan-specific.Conclusions: Testing RA patients to learn their ACPA status and increasing use of abatacept among high-titer ACPA patients result in a small increase in the total budget (<2 cents PMPM).
32963052 Impact of the COVID-19 pandemic on the disease course of patients with inflammatory rheuma 2021 Feb OBJECTIVES: To investigate whether the transient reduction in rheumatology services imposed by virus containment measures during the COVID-19 pandemic was associated with disease worsening in axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA). METHODS: Patient-reported disease activity assessed during face-to-face visits and/or via a smartphone application were compared between three periods of each 2 months duration (before, during and after the COVID-19-wave) from January to June 2020 in 666 patients with axSpA, RA and PsA in the Swiss Clinical Quality Management cohort. RESULTS: The number of consultations dropped by 52%, whereas the number of remote assessments increased by 129%. The proportion of patients with drug non-compliance slightly increased during the pandemic, the difference reaching statistical significance in axSpA (19.9% vs 13.2% before the pandemic, p=0.003). The proportion of patients with disease flares remained stable (<15%). There was no increase in mean values of the Bath Ankylosing Disease Activity Index, the Rheumatoid Arthritis Disease Activity Index-5 and the Patient Global Assessment in patients with axSpA, RA and PsA, respectively. CONCLUSION: A short interruption of in-person patient-rheumatologist interactions had no major detrimental impact on the disease course of axSpA, RA and PsA as assessed by patient-reported outcomes.
32924098 Enzymatically crosslinked tyramine-gellan gum hydrogels as drug delivery system for rheuma 2021 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint synovial inflammation, as well as cartilage and bone tissue destruction. Current strategies for the treatment of RA can reduce joint inflammation, but the treatment options still represent stability concerns since they are not sufficient and present a fast clearing. Thus, several drug delivery systems (DDS) have been advanced to tackle this limitation. Injectable gellan gum (GG) hydrogels, reduced by physical crosslinking methods, also being proposed as DDS, but this kind of crosslinking can produce hydrogels that become weaker in physiological conditions. Nevertheless, enzymatic crosslinking emerged as an alternative to increase mechanical strength, which can be adjusted by the degree of enzymatic crosslinking. In this study, tyramine-modified gellan gum (Ty-GG) hydrogels were developed via horseradish peroxidase (HRP) crosslinking; and betamethasone was encapsulated within, to increase the specificity and safety in the treatment of patients with RA. Physicochemical results showed that it was possible to modify GG with tyramine, with a degree of substitution of approximately 30%. They showed high mechanical strength and resistance, presenting a controlled betamethasone release profile over time. Ty-GG hydrogels also exhibited no cytotoxic effects and do not negatively affected the metabolic activity and proliferation of chondrogenic primary cells. Furthermore, the main goal was achieved since betamethasone-loaded Ty-GG hydrogels demonstrated to have a more effective therapeutic effect when compared with the administration of betamethasone alone. Therefore, the developed Ty-GG hydrogels represent a promising DDS and a reliable alternative to traditional treatments in patients with RA.
32739893 Effect on Costs and Quality-adjusted Life-years of Treat-to-target Treatment Strategies In 2021 Apr OBJECTIVE: Our study aimed to evaluate the cost effectiveness of initiating tocilizumab (TCZ) ± methotrexate (MTX) versus initiating MTX as treat-to-target treatment strategies over 5 years in early disease-modifying antirheumatic drug (DMARD)-naïve rheumatoid arthritis (RA). METHODS: Data on resource use were collected with questionnaires at baseline, 3, 6, 12, and 24 months, and yearly thereafter, and were converted to costs using Dutch reference prices. Quality-adjusted life-years (QALY) were calculated using the EQ5D5L, with utility based on Dutch tariff or estimated by the Health Assessment Questionnaire. To account for missing cost data and QALY data and for sample uncertainty, first bootstraps (10,000 samples) were obtained. Second, single imputation using chained equations nested within these bootstrap samples was performed. An economic evaluation was performed for TCZ + MTX and TCZ, compared to MTX, as initial treatment in a treat-to-target strategy from a healthcare and societal perspective over 5 years. Several sensitivity analyses were performed. RESULTS: Mean differences in QALY were small and not significant (TCZ + MTX vs MTX: 0.06, 95% CI -0.02 to 0.13; TCZ vs. MTX: -0.03, 95% CI -0.05 to 0.11). Limited savings in indirect nonhealthcare costs and productivity loss costs (for TCZ only) were observed, but these did not compensate for the higher medication costs. Sensitivity analyses did not materially change these findings, although lower-priced TCZ, or reserving TCZ as initial therapy for prognostically unfavorable RA patients, improved cost effectiveness considerably but did not individually lead to a strategy being cost effective. CONCLUSION: Based on our analyses, early initiation of TCZ + MTX is not cost effective compared to MTX initiation in a step-up treat-to-target treatment strategy over 5 years in early RA patients.
31960737 Efficacy and safety of tacrolimus in patients with rheumatoid arthritis - A systematic rev 2021 Jan OBJECTIVES: To evaluate the efficacy and safety of tacrolimus in adult patients with rheumatoid arthritis (RA) by using the GRADE approach. METHODS: We searched PubMed, Japana Centra Revuo Medicina Web (Ichu-shi web), and the Cochrane Database of Systematic Reviews. Articles fulfilling the predefined inclusion criteria were appraised and used for meta-analysis. The primary outcomes were American College of Rheumatology 20 (ACR20) and serum creatinine elevation. Other outcomes included ACR50, ACR70, changes in C-reactive protein, modified Health Assessment Questionnaire Disability Index, gastrointestinal disorders, metabolic and nutritional disorders, and infections and infestations. RESULTS: We identified five randomized controlled studies, four of which compared tacrolimus to placebo and were included in the meta-analysis. The risk ratio of ACR20 achievement was 1.71 (95% confidence interval [CI] 1.20-2.42) for 1-2 mg/day and 2.30 (95% CI 1.79-2.96) for 3 mg/day. The risk ratio of creatinine elevation was 1.95 (95% CI 1.18-3.23) for 1-2 mg/day and 3.81 (95% CI 2.43-5.99) for 3 mg/day. CONCLUSION: Tacrolimus is effective with acceptable safety in the management of RA.
31867699 Clinical Pharmacokinetics of Upadacitinib: Review of Data Relevant to the Rheumatoid Arthr 2020 May Upadacitinib is a Janus kinase 1 inhibitor developed for treatment of moderate to severe rheumatoid arthritis (RA) and was recently approved by the US Food and Drug Administration for this indication in adults who have had an inadequate response or intolerance to methotrexate. Upadacitinib is currently under regulatory review by other agencies around the world. Ongoing trials are investigating the use of upadacitinib in other inflammatory autoimmune diseases. In this article, we review the clinical pharmacokinetic data available to date for upadacitinib that supported the clinical development program in RA and ultimately regulatory applications for upadacitinib in treatment of patients with moderate to severe RA.
32547009 Toxicological and Anti-Rheumatic Potential of Trachyspermum ammi Derived Biogenic Selenium 2020 PURPOSE: The existing treatment modalities for rheumatoid arthritis are less effective and safe, therefore it is essential to develop new treatments that particularly target the inflamed joints with decreased off-target side-effects. The current study proposes a nanoparticle-based therapeutic approach to target the anti-oxidant defense system of arthritic Balb/c mice. METHODS: Biogenic selenium nanoparticles (SeNPs) were synthesized by using Trachyspermum ammi seed extract and were evaluated for their toxicological, as well as their therapeutic potential in collagen-induced arthritic mice. RESULTS: The tested doses of SeNPs had no significant toxic effects on liver, kidney, spleen, and serum biochemical parameters in comparison to healthy mice. The SeNPs treatment reduced the disease severity, as demonstrated by decreased paw edema along with reduced lymphocytic cellular infiltration in the histopathological findings. SeNPs also revealed dose-independent improvement in the redox state of inflamed synovium by significantly improving the activity of antioxidant enzymes in comparison to the arthritic controls. CONCLUSION: It is therefore concluded that nano-selenium in combination with TAE extract showed enhanced therapeutic efficacy as compared to their individual effects.
32997565 Evaluation of retinal vascularization by optical coherence tomography angiography (OCTA) i 2021 Jul PURPOSE: To measure the retinal capillary density quantitatively with optical coherence tomography angiography (OCTA) in patients with rheumatoid arthritis (RA) and healthy controls (HCs), and to evaluate the relationship between OCTA findings and RA disease activity. METHODS: In this cross-sectional study, 106 eyes of RA patients and 71 eyes of HCs were evaluated. RA patients were divided into inactive (DAS28 < 3.2) and active (DAS28 ≥ 3.2) subgroups. Retinal capillary plexus density (CPD) was obtained from the superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary capillary (RPC). RESULTS: In RA patients and HCs, the CPD (%) was 50.99 ± 3.30 and 52.08 ± 2.36 (p = .013) in the SCP, 55.65 ± 5.73 and 57.53 ± 4.60 (p = .019) in the DCP, and 49.98 ± 2.25 and 49.93 ± 2.25 (p = .947) in the RPC blood supply regions, respectively. In inactive and active RA patients, the CPD (%) was 51.01 ± 2.92 and 50.97 ± 3.73 (p = .947) in the SCP, 55.02 ± 5.70 and 56.40 ± 5.74 in the DCP (p = .229), and 50.34 ± 2.23 and 49.55 ± 2.22 (p = .079) in the RPC blood supply regions, respectively. DAS28 was negatively correlated with CPD in RPC blood supply region (Rho = -0.272, p = .006). CONCLUSION: In RA, retinal CPD in the macula is lower than HCs. Although retinal CPD is not generally different in active and inactive RA patients, capillaries in the optic disc may be affected by disease activity.
31371657 Longterm, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospecti 2020 Jul 1 OBJECTIVE: To assess longterm safety in a US cohort of patients with rheumatoid arthritis (RA) treated with adalimumab (ADA) in real-world clinical care settings. METHODS: This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry. Patients were adults (≥ 18 yrs) who initiated ADA treatment between January 2008 and June 2017, and who had at least 1 followup visit. RESULTS: In total, 2798 ADA initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean disease duration of 8.3 years. Nearly half (48%) were biologic-naive, and 9% were using prednisone ≥ 10 mg at ADA initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44, 95% CI 2.45-4.84) than in subsequent years, while other measured adverse effects did not vary substantially by duration of exposure. The median time to ADA discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION: Analysis of longterm data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with ADA treatment and provides guidance for physicians prescribing ADA for extended periods.
33315114 Lung Cancer Survival in Patients With Autoimmune Disease. 2020 Dec 1 IMPORTANCE: Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. OBJECTIVE: To determine the association between autoimmune disease and lung cancer survival. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. EXPOSURE: Presence of autoimmune disease. MAIN OUTCOMES AND MEASURES: Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. RESULTS: Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. CONCLUSIONS AND RELEVANCE: Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.
32341443 Traditional cardiovascular risk factors and residual disease activity are associated with 2020 Sep Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular events. Ultrasound examination of the carotid arteries can show the presence of plaques and detect the atherosclerotic subclinical process through the evaluation of intima-media thickness (cIMT) and carotid segmental distensibility (cCD). The aim of the present study was to identify which factors could independently influence the evolution of atherosclerosis (plaques, cIMT, and cCD) after 1 year of follow-up in a sample of patients with RA. A total of 137 patients with RA without previous cardiovascular (CV) events were enrolled at baseline, and 105 (M/F: 21/84, age 59.34 ± 11.65 years) were reassessed after one year using ultrasound of carotid arteries to detect atheromatous plaques and to measure cIMT and cCD. After one year, all the indices of subclinical atherosclerosis worsened with respect to baseline (Δ-cIMT = 0.030 ± 0.10 mm, p = 0.005; Δ-cCD = -1.64 ± 4.83, 10-3/KPa, p = 0.005; Δ-plaques = 8.6%, p = 0.035). Traditional CV risk factors (age, mean arterial pressure, and diabetes) and corticosteroid therapy were independently associated with the worsening of subclinical atherosclerosis. Interestingly, when considering RA patients divided according to the degree of disease activity score 28 with C-reactive protein (DAS28 [CRP] ≥2.6), the worsening of subclinical atherosclerosis indices was detectable exclusively in the group of patients with active disease. Our longitudinal study supports the hypothesis of a key role of both traditional CV risk factors and the inflammatory activity of arthritic disease in the progression of subclinical atherosclerosis in RA patients. In addition, corticosteroids might have a deleterious effect.