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ID PMID Title PublicationDate abstract
34010670 The emerging roles of exosomes in autoimmune diseases, with special emphasis on microRNAs 2021 Jul Autoimmune diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic vasculitis, dermatomyositis, systemic sclerosis (SSc), mixed connective tissue disease, autoimmune hemolytic anemia, autoimmune thyroiditis (AITD) and ulcerative colitis. Exosomes exist in body fluids, including blood, saliva, urine, cerebrospinal fluid and milk. They are mainly derived from the invagination of intracellular lysosomal particles, which are released into the extracellular matrix after fusion of the outer membrane of the exosomes with the cell membrane. Exosomes mediate intercellular communication and regulate the biological activity of receptor cells by carrying proteins, nucleic acids and lipids. Evidences show that exosomes are involved in the pathogenesis of various autoimmune diseases. In view of the important roles of exosomes in autoimmune diseases, this work systematically reviewed the effects of exosomes on the pathogenesis of autoimmune diseases, especially the regulatory roles of exosome derived microRNAs (miRNAs) in the pathogenesis of RA, SLE, dermatomyositis, SSc, AITD and ulcerative colitis. The review of the roles of exosomes in autoimmune diseases will help to clarify the pathogenesis of these diseases and explore new diagnostic markers and therapeutic targets.
33990365 Uptake of influenza vaccination among persons with inflammatory bowel disease, multiple sc 2021 Apr BACKGROUND: Individuals with immune-mediated inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, are at increased risk for influenza and related complications. We examined and compared the uptake of influenza vaccination among people with and without these diseases, as well as the influence of psychiatric comorbidity on vaccine uptake. METHODS: Using administrative data from Apr. 1, 1984, to Mar. 31, 2016, we conducted a retrospective matched cohort study in Manitoba, Canada. We matched persons 18 years of age or older who had a diagnosis of inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis (the immune-mediated inflammatory disease cohorts) with persons who did not have these diagnoses (the control cohorts) on age, sex and region. We then identified cohort members with any mood or anxiety disorder (depression, anxiety disorders, bipolar disorder). We identified influenza vaccinations through billing codes. Using binomial regression, we modelled the difference in the proportion of the immune-mediated inflammatory disease and matched cohorts vaccinated annually, with adjustment for sociodemographic characteristics, comorbidity and immune therapy. We tested additive interaction effects between a person's cohort and presence of a mood or anxiety disorder. RESULTS: We identified 32 880 individuals with 1 or more immune-mediated inflammatory diseases (10 148 with inflammatory bowel disease, 6158 with multiple sclerosis and 16 975 with rheumatoid arthritis) and a total of 164 152 controls. In fiscal year 2015, 8668 (41.3%, 95% confidence interval [CI] 40.6% to 42.0%) of the 20 982 persons with an immune-mediated inflammatory disease received an influenza vaccination, a rate higher than among controls (35 238 of 104 634; 33.7%, 95% CI 33.4% to 34.0%). After adjustment, participants with an immune-mediated inflammatory disease but no mood or anxiety disorder had 6.44% (95% CI 5.79% to 7.10%) greater uptake of vaccination than participants without such a disease. Among participants without an immune-mediated inflammatory disease, having a mood or anxiety disorder was associated with 4.54% (95% CI 4.20% to 4.89%) greater uptake of vaccination. However, we observed a subadditive interaction between immune-mediated inflammatory disease and psychiatric status (-1.38%, 95% CI -2.26% to -0.50%). INTERPRETATION: Uptake of influenza vaccination was consistently low in populations with immune-mediated inflammatory disease, and although psychiatric morbidity is associated with greater vaccine uptake by Manitobans, it negatively interacts with these diseases to reduce uptake. Changes in care delivery are needed to mitigate this gap in care.
33369650 Decreased serum ACE2 levels in patients with connective tissue diseases. 2021 Sep 1 OBJECTIVE: To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs). METHODS: Serum samples from healthy subjects and patients with SLE, systemic sclerosis (SSc), primary Sjögren's syndrome (SS) and RA were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method, respectively, and analysed for associations with clinical features and concurrent medications. RESULTS: In total, 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed. CONCLUSION: The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggest ACE2 levels are not affected by most of the treatments.
33913684 Dual-Stimuli Responsive Polymeric Micelles for the Effective Treatment of Rheumatoid Arthr 2021 May 12 The nontargeted distribution and uncontrolled in vivo release of drugs impede their efficacy in the treatment of rheumatoid arthritis (RA). Delivering drugs to arthritic joints and releasing drugs on demand are a feasible solution to achieve the effective treatment of RA. In this paper, we report a facile method to assemble dual-stimuli responsive polymeric micelles from polyethylene glycol-phenylboric acid-triglycerol monostearate (PEG-PBA-TGMS, PPT) conjugates with the aim of delivering dexamethasone (Dex) to arthritic joints and controlling the release of Dex by inflammatory stimuli. We show that the release of Dex from the PPT micelles is accelerated in response to acidic pH and overexpressed matrix metalloproteinases. In an adjuvant-induced arthritis model, the PPT micelles preferentially accumulate in arthritic joints and show an excellent therapeutic efficacy after being intravenously administrated. Our results highlight the potential of the dual stimuli-responsive micelles as a promising therapeutic option for the effective treatment of inflammatory diseases.
34128886 Fusion proteins of biologic agents in the treatment of rheumatoid arthritis (RA): A networ 2021 Jun 18 BACKGROUND: To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using network meta-analysis to rank those according to their performance medicines. The performance of these processes is ranked according to the results of the analysis and an explanatory study of the possible results is carried out. METHODS: Multiple databases including PubMed, EMBASE, and Cochrane Library were used to identify applicable articles and collect relevant data to analyze using STATA (14.0) software. The literature included in this study was divided into a combination of a placebo, methotrexate (MTX), and an observation group (1 of the 3 drugs). The last search date was December 12, 2019. RESULTS: A total of 19 eligible randomized controlled trials of fusion proteins biologics were identified, a total of 1109 papers were included, and the results showed that the ETN + MTX had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking curve of 91.6, was significantly superior (P < .05). Patients who had received ETN or ETN + MTX or ANA had effective compared with patients who had received placebo (95% CI 1.28%-8.47%; 1.92%-19.18%; 1.06%-10.45%). CONCLUSIONS: 1. The combination of ETN and MTX had the highest probability of optimal treatment compared to other drugs and 2. ENT, ENT + MTX, and ANA were effective in the treatment of RA compared to placebo.
33065691 Cervical Spinal Fusion in Adult Patients With Rheumatoid Arthritis: A National Analysis of 2021 Jan 1 STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of this study was to utilize the National Readmission Database to determine the national estimates of complication and 90-day readmission rates associated with cervical spinal fusion in adult patients with rheumatoid arthritis (RA). SUMMARY OF BACKGROUND: RA patients who undergo cervical spine surgery are known to be at high risk for readmissions, which are costly and may not be reimbursed by Medicare. METHODS: The National Readmission Database was queried for adults (>18 years) diagnosed with RA undergoing cervical spine fusion. Patient, operative, and hospital factors were assessed in bivariate analyses. Independent risk factors for readmissions were identified using stepwise multivariate logistic regression. RESULTS: From 2013 to 2014, a total of 5597 RA patients (average age: 61.5 ± 11.2 years, 70.9% female) underwent cervical spine fusion. A total of 691 (12.3%) patients were readmitted within 90 days (). Index inpatient complications included dysphagia (readmitted: 7.9% vs. non-readmitted: 5.1%; P = 0.003), urinary tract infection (UTI) (8.8% vs. 3.7%; P < 0.001), respiratory-related complications (7.6% vs. 3.4%; P < 0.001), and implant-related complications (5.4% vs. 2.7%; P < 0.001). Multivariate logistic regression demonstrated the following as the strongest independent predictors for 90-day readmission: intraoperative bleeding (odds ratio [OR]: 3.6, P = 0.001), inpatient Deep Vein Thrombosis (DVT) (OR 4.1, P = 0.004), and patient discharge against medical advice (OR 33.5, P = 0.001). CONCLUSION: Readmission rates for RA patients undergoing cervical spine surgery are high and most often due to postoperative infection (septicemia, UTI, pneumonia, wound). Potential modifiable factors which may improve outcomes include minimizing intraoperative blood loses, postoperative DVT prophylaxis, and discharge disposition. LEVEL OF EVIDENCE: 3.
33391544 Tofacitinib restores the balance of γδTreg/γδT17 cells in rheumatoid arthritis by inhi 2021 Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, γδTreg/γδT17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp3(-/-) mice were introduced to assess the influence of NLRP3 on γδT17 cell activation in RA. Results: TOF treatment decreased levels of γδT17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the γδTreg/γδT17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1β via downregulation of NLRP3. Furthermore, experiments using Nlrp3 (-/-) mice verified that the NLRP3 inflammasome mediated the effect of TOF on γδT17 cell activation. Conclusions: Recovery of γδTreg/γδT17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated γδT17 cell activation.
33670600 Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially 2021 Feb 18 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints. Inflammation, new blood vessel formation (angiogenesis) and bone resorption (osteoclastogenesis) are three key processes involved in the joint damage and deformities of arthritis. Various gut microbiota-derived metabolites are implicated in RA pathogenesis. However, there is barely any information about the impact of two such metabolites, indole-3-aldehyde (IAld) and indole-3-acetic acid (I3AA), on arthritis-related processes. We conducted a comparative analysis of IAld and I3AA using established cell-based models to understand how they might influence RA pathogenesis. Although structurally similar, the bioactivities of these two metabolites were profoundly different. IAld but not I3AA, inhibited the expression of pro-inflammatory cytokines (IL-1β and IL-6) in RAW 264.7 (RAW) cells stimulated with heat-killed M. tuberculosis sonicate (Mtb) and lipopolysaccharide (LPS). IAld also exhibited pro-angiogenic activity and pro-osteoclastogenic activity. In contrast, I3AA exhibited anti-angiogenic activity on endothelial cell tube formation but had no effect on osteoclastogenesis. Both IAld and I3AA have been proposed as aryl hydrocarbon receptor (AhR) agonists. Use of CH-223191, an inhibitor of the AhR, suppressed the anti-angiogenic activity of I3AA but failed to mitigate the effects of IAld. Further investigation of the anti-inflammatory activities of IAld and I3AA in LPS-treated RAW cells indicated that inhibition of MyD88-dependent activation of NF-κB and MAPK pathways was not likely involved. Our results suggest that the relative bioavailability of these indole derivatives may differentially impact RA progression and possibly other diseases that share similar cellular processes.
34925336 Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheu 2021 Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2(hi) subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade in vitro. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated in vivo by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade in vivo reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2(hi) circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.
33169522 Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Inter 2021 May OBJECTIVE: Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials have been performed using interleukin-10 (IL-10), an antiinflammatory cytokine, as a potential treatment of RA, the therapeutic effects of IL-10 have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. This study was undertaken to engineer an IL-10-serum albumin (SA) fusion protein and evaluate its effects in 2 murine models of RA. METHODS: SA-fused IL-10 (SA-IL-10) was recombinantly expressed. Mice with collagen antibody-induced arthritis (n = 4-7 per group) or collagen-induced arthritis (n = 9-15 per group) were injected intravenously with wild-type IL-10 or SA-IL-10, and the retention of SA-IL-10 in the lymph nodes (LNs), immune cell composition in the paws, and therapeutic effect of SA-IL-10 on mice with arthritis were assessed. RESULTS: SA fusion to IL-10 led to enhanced accumulation in the mouse LNs compared with unmodified IL-10. Intravenous SA-IL-10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive alternatively activated macrophages, reduced IL-17A levels in the paw-draining LN, and protected joint morphology. Intravenous SA-IL-10 treatment showed similar efficacy as treatment with an anti-tumor necrosis factor antibody. SA-IL-10 was equally effective when administered intravenously, locally, or subcutaneously, which is a benefit for clinical translation of this molecule. CONCLUSION: SA fusion to IL-10 is a simple but effective engineering strategy for RA therapy and has potential for clinical translation.
32306287 Serum CRP, MDA, Vitamin C, and Trace Elements in Bangladeshi Patients with Rheumatoid Arth 2021 Jan Rheumatoid arthritis (RA) is an autoimmune disorder that is a painful health crisis. This study aimed to assess the serum C-reactive protein (CRP), malondialdehyde (MDA), non-enzymatic antioxidant (vitamin C), and trace elements (Zn, Cu, Mn, and Fe) in RA patients, and thereby correlate these parameters with the association of RA. This study included 20 Bangladeshi RA patients and 20 normal healthy volunteers as control subjects. CRP level was determined using a laboratory-based latex agglutination-enhanced immunoassay. The lipid peroxidation level was determined by measurement of the serum level of MDA. Non-enzymatic antioxidant vitamin C was assessed by UV spectrophotometric method. Trace elements were determined by atomic absorption spectroscopy (AAS). Our study observed significantly higher concentrations of CRP (p < 0.001) and MDA (p < 0.001), and significantly lower concentrations of vitamin C (p < 0.001) in the RA patient. The mean values of Zn, Cu, Mn, and Fe were 6.62 ± 0.34, 1.42 ± 0.17, 7.51 ± 0.23, and 29.25 ± 0.41 ppm for the RA patients respectively and 13.57 ± 9.13, 1.15 ± 0.17, 1.59 ± 0.18, and 62.47 ± 5.25 ppm for the control subjects, consequently. There was a significant difference (p < 0.05) in the trace element levels between the RA patients and control subjects. Our study suggests that a higher concentration of CRP and MDA, lower levels of vitamin C, and altered trace elements may be linked to RA.
34496979 Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regressio 2021 Sep 8 BACKGROUND: Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. METHODS: Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score < 2.6. Cutoff values to dichotomize baseline variables maximizing the detection of remission were obtained from Receiver Operator Curve analyses. Baseline dichotomized and categorical variables were analyzed altogether in a stepwise logistic regression model. Odds of attaining response at Weeks 24 and 128 were estimated for each significant predictor. RESULTS: At Week 24 and Week 128, 27% (66/241) and 42% (91/219) of patients in the ETN + MTX group achieved remission. On average, patients achieving remission were younger and had lower baseline ESR, lower Physician Global Assessment (PGA) scores, lower total Health Assessment Questionnaire (HAQ) scores, and lower visual analog scale (VAS) Pain scores compared with patients who did not achieve remission. The best subset of baseline variables predicting Week 24 remission in the stepwise regression model were age ≤ 49 years (odds ratio [OR] 2.93), body mass index (BMI) > 28.5 kg/m(2) (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. CONCLUSIONS: In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00848354.
34256502 Evaluation of pulmonary involvement in systemic rheumatic diseases with high resolution co 2021 Jun INTRODUCTION: The objective of this study was to investigate the clinical and radiological features and pulmonary function tests (PFTs) in patients with the pulmonary involvement of systemic rheumatic diseases (SRDs). MATERIALS AND METHODS: This study was conducted as a retrospective and single-center study. Patients diagnosed with an SRD and admitted/referred to the department of chest diseases of our hospital between January 2015 and June 2019 were enrolled. All patients were evaluated using High Resolution Computed Tomography (HRCT) and PFT. RESULT: This study included 68 patients (15 males, 53 females) with a mean age of 62.38 ± 12.4 years. Forty-one (60.2%) patients had diagnosis of rheumatoid arthritis (RA), 10 (14.7%) patients had sjögren's syndrome (SS), 8 (11.7%) patients had systemic lupus erythematosus (SLE), 6 (8.8%) patients had systemic sclerosis (SSc), and 3 (4.4%) patients had mixed connective tissue disease (MCTD). While RA, SLE, MCTD patients were more commonly symptomatic, most of the SS patients were asymptomatic. Overall, 30 (44.1%) patients had normal PFT. Although 30 (%44.1) patients were asymptomatic and 30 (%44.1) patients had normal PFTs, at least one imaging finding was found in all patients according to HRCT imaging. "Bronchiectasis" was the most common HRCT finding in RA, followed by "chronic fibrotic changes" and "peribronchial thickening". "Chronic fibrotic changes" and "peribronchial thickening" were the most common changes in SS. Similarly, "peribronchial thickening" was the most common radiologic finding in SLE. As for SSc, "chronic fibrotic changes", "interlobular septal thickening", and "pleural effusion" were the most common radiologic findings. CONCLUSIONS: Pulmonary involvement in systemic rheumatic diseases can occur with various radiological images even in asymptomatic patients. PFTs can be normal as well as an obstructive, restrictive or mixed pattern can be seen. Heterogeneous and combined HRCT findings can be seen in SRD patients.
34351924 Effect of comorbid mood and anxiety disorders on breast and cervical cancer screening in i 2021 We aimed to examine rates of breast and cervical cancer screening in women with immune-mediated inflammatory diseases (IMID), including inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus a matched cohort with IMID; and examine the association of psychiatric comorbidity with screening in these populations. We conducted a retrospective cohort study in Manitoba, Canada using administrative data. We identified women with IBD, MS and RA, and controls without these IMID matched on age and region. Annually, we identified individuals with any active mood/anxiety disorder. Using physician claims, we determined the proportion of each cohort who had cervical cancer screening within three-year intervals, and mammography screening within two-year intervals. We modeled the difference in the proportion of the IMID and matched cohorts who underwent mammography; and pap tests using log-binomial regression with generalized estimating equations, adjusting for sociodemographics, comorbidity and immune therapy use. We tested for additive interactions between cohort and mood/anxiety disorder status. During 2006-2016, we identified 17,230 women with IMID (4,623 with IBD, 3,399 with MS, and 9,458 with RA) and 85,349 matched controls. Having an IMID was associated with lower (-1%) use of mammography; however, this reflected a mixture of more mammography in the IBD cohort (+2.9%) and less mammography in the MS (-4.8 to -5.2%) and RA (-1.5%) cohorts. Within the IBD, MS and RA cohorts, having an active mood/anxiety disorder was associated with more mammography use than having an inactive mood/anxiety disorder. The MS and RA cohorts were less likely to undergo Pap testing than their matched cohorts. In the absence of an active mood/anxiety disorder, the IBD cohort was more likely to undergo Pap testing than its matched cohort; the opposite was true when an active mood/anxiety disorder was present. Among women with an IMID, mood/anxiety disorder influence participation in cancer screening.
32955037 Correlation between sarcopenia and nailfold microcirculation, serum 25-hydroxycholecalcife 2021 Sep AIMS: To investigate the correlation between sarcopenia and nailfold microcirculation and serum 25-hydroxycholecalciferol [25 (OH) D3] (instead of 25-hydroxyvitamin D) and IL-17 levels in female rheumatoid arthritis (RA) patients. METHODS: 130 female rheumatoid arthritis (RA) patients and 80 healthy controls were tested. Nailfold capillaroscopic scores (NFCS) were measured. Bioimpedance analysis (BIA) was used to measure skeletal muscle mass. Enzyme-linked immunosorbant assay (ELISA) was used to detect the levels of IL-17, IL-6 and TNF-α. Serum 25 (OH) D3 concentration was determined by photochemical immunoassay. The correlation was analyzed by Pearson's correlation, and the influencing factors were analyzed by binary logistic regression. RESULTS: (1) Compared with the control group, NFCS and serum IL-17 levels were higher in the RA group, while the serum 25 (OH) D3 and skeletal mass index (SMI) were lower. (2) Pearson correlation analysis found: SMI was positively correlated with 25 (OH) D3 (r=0.515, P<0.001), SMI was negatively correlated with IL-17 (r=-0.468, P<0.001), SMI was negatively correlated with NFS (r = -0.229, P=0.009); (3) Logistic regression analysis: serum 25 (OH) D3 was a protective factor for sarcopenia (OR=0.392, P=0.016); IL-17, C-reactive protein, and NFS were risk factors for sarcopenia (OR=1.516, P=0.049; OR=1.469, P=0.045; OR=3.497, P=0.002). CONCLUSION: Secondary sarcopenia in RA is common and is closely related to microcirculation abnormalities. Increased NFCS is a risk factor for sarcopenia. Decreased serum 25 (OH) D3 levels and increased IL-17 are also risk factors for sarcopenia, but the mechanisms involved in sarcopenia and microcirculation abnormalities need further investigation.
34653564 Thermoresponsive polymeric dexamethasone prodrug for arthritis pain. 2021 Nov 10 Intra-articular (IA) glucocorticoids (GC) are commonly used for clinical management of both osteoarthritis and rheumatoid arthritis, but their efficacy is limited by the relatively short duration of action and associated side effects. To provide sustained efficacy and to improve the safety of GCs, we previously developed a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based dexamethasone (Dex) prodrug. Serendipitously, we discovered that, by increasing the Dex content of the prodrug to unusually high levels, the aqueous solution of the polymeric prodrug becomes thermoresponsive, transitioning from a free-flowing liquid at 4 °C to a hydrogel at 30 °C or greater. Upon IA injection, the prodrug solution forms a hydrogel (ProGel-Dex) that is retained in the joint for more than 1 month, where it undergoes gradual dissolution, releasing the water-soluble polymeric prodrug. The released prodrug is swiftly internalized and intracellularly processed by phagocytic synoviocytes to release free Dex, resulting in sustained amelioration of joint inflammation and pain in rodent models of inflammatory arthritis and osteoarthritis. The low molecular weight (6.8 kDa) of the ProGel-Dex ensures rapid renal clearance once it escapes the joint, limiting systemic GC exposure and risk of potential off-target side effects. The present study illustrates the translational potential of ProGel-Dex as a potent opioid-sparing, locally delivered adjuvant analgesic for sustained clinical management of arthritis pain and inflammation. Importantly, the observed thermoresponsive properties of the prodrug establishes ProGel as a platform technology for the local delivery of a broad spectrum of therapeutic agents to treat a diverse array of pathological conditions.
33349110 Drug-induced subacute cutaneous lupus erythematosus associated with abatacept. 2021 Apr Numerous drugs have been linked to the induction or exacerbation of systemic cutaneous lupus erythematosus (SCLE). This report presents the third case of the biologic abatacept as an exacerbating medication for SCLE. A 73-year old woman with a remote history of subacute cutaneous lupus and rheumatoid arthritis, well controlled on hydroxychloroquine, presented with worsening annular erythematous, slightly scaly plaques on her forearms and hands. She had been started on abatacept a month prior. She was diagnosed with SCLE exacerbated by abatacept given the clinical findings, time course, and skin biopsy with interface dermatitis. Her skin eruption cleared completely several months later after discontinuing abatacept and switching to tociluzumab, while remaining on hydroxychloroquine. This case highlights the need to consider abatacept as a potential exacerbating medication for SCLE in any patient with a new photodistributed papulosquamous eruption.
35185862 Systematic Review of Safety and Efficacy of Second- and Third-Generation CD20-Targeting Bi 2021 BACKGROUND: B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use of rituximab, the first anti-CD20 monoclonal antibody (mAb). Following rituximab, second- and third-generation anti-CD20 mAbs have been developed and tried in immune-mediated diseases, including obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab. However, their safety and efficacy has not been systematically reviewed. OBJECTIVE: To evaluate safety and efficacy of obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics. METHODS: The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 22 July 2021 concentrating on immune-mediated disorders. RESULTS: The literature search identified 2220 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 27 articles were finally included in a narrative synthesis. CONCLUSIONS: Obinutuzumab has shown promising results in a case series of patients with phospholipase A(2) receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. Ocrelizumab has been approved for the use in patients with relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab was also tested in patients with rheumatoid arthritis, demonstrating promising results, and in systemic lupus erythematosus, revealing mixed results; however, in these conditions, its use was associated with increased risk of serious infections. Ofatumumab received approval for treating patients with relapsing-remitting multiple sclerosis. Moreover, ofatumumab showed promising results in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis, and systemic lupus erythematosus, as well as mixed results in phospholipase A(2) receptor-associated membranous nephropathy. Ublituximab was assessed in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, with promising results, however, the included number of patients was too small to conclude. Veltuzumab was tested in patients with immune thrombocytopenia resulting in improved platelet counts. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD4201913421.
32910152 Efficacy and serious adverse events profile of the adjuvanted recombinant zoster vaccine i 2021 Mar 2 ABSTRACT OBJECTIVE: In the ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials, the adjuvanted recombinant zoster vaccine (RZV) demonstrated ≥90% efficacy in preventing herpes zoster (HZ) in all age groups ≥50 years. Given the increased HZ risk associated with certain underlying autoimmune diseases or their treatment regimes, we conducted a post hoc analysis of RZV's efficacy against HZ and safety profile [specifically, the occurrence of serious adverse events (SAEs)] in ZOE-50/70 participants who reported pre-existing potential immune-mediated diseases (pIMDs) at enrolment and were not on immunosuppressive therapies. METHODS: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomized to receive two doses of RZV or placebo 2 months apart. In this subgroup analysis of participants with at least one pIMD at enrolment, the efficacy was calculated for two-dose recipients who did not develop confirmed HZ before 30 days post-dose 2. SAE occurrence was evaluated for all participants who received at least one dose. RESULTS: Of the 14 645 RZV and 14 660 placebo recipients from the ZOE-50/70 studies, 983 and 960, respectively, reported at least one pre-existing pIMD at enrolment and were included in these analyses. The most frequent pre-existing conditions were psoriasis, spondyloarthropathy and RA. Efficacy against HZ was 90.5% (95% CI: 73.5, 97.5%) overall with the lowest being 84.4% (95% CI: 30.8, 98.3%) in the 70-79-year-old age group. SAEs and fatal SAEs were similar between RZV and placebo recipients. CONCLUSION: In ZOE-50/70 participants with pre-existing pIMDs, RZV was highly efficacious against HZ and SAE incidence was similar between RZV and placebo recipients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).
34136971 Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFΠ2021 Nov OBJECTIVES: We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA). MATERIALS AND METHODS: We enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004-2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan-Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded. RESULTS: Two hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50-3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07-3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22-0.73). CONCLUSIONS: Survival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI. Key Points • Drug survival in PsA patients was confirmed be greater for the first bDMARD administered. • In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches. • Female sex may constitute a predisposing risk factor for flare and therapeutic switches. • Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.