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ID PMID Title PublicationDate abstract
35160074 Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-L 2022 Jan 26 We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.
34384858 The effect of association of aspirin and omega 3 in rat temporomandibular joint with induc 2022 Jan This study aimed to evaluate the effects of omega-3 (ω3) polyunsaturated fatty acids, in association with aspirin (AA), on the morphology of cytokine release in the temporomandibular joint (TMJ) of rats induced with rheumatoid arthritis (IR) by injecting 100 μL of complete Freund's adjuvant with bovine type II collagen at the tail base. Thirty-two adult male rats were divided into treatment groups: Sham, treated with 0.9% sodium chloride (NaCl) p.o.; IR-control, treated with 0.9% NaCl p.o.; IR-ω3 treated with ω3 PUFAS (85 mg/kg/day p.o.); and IR-ω3 + AA treated with ω3 (85 mg/kg/day p.o.) + AA (20 mg/kg/day i.p.). After maintained treatment for seven days, the animals were euthanized. Bilateral TMJs from each rat were removed and one was subjected to histological immunoassays and enzyme-linked immunosorbent assays to assess interleukin (IL)-1β, tumor necrosis factor-α, and IL-10 levels. Data analysis was performed using the Kruskal-Wallis and Dunn tests. In the IR-ω3 and IR-ω3 + AA groups, the TMJ was greater than in the IR-control group (P < 0.0001). The addition of AA did not improve the effects of ω3 (P = 0.0698). Similarly, the addition of AA conferred no additional effects on the cytokine levels (P > 0.05); however, it increased the proteoglycan density, compared with ω3 alone. We found that ω3 exhibited anti-inflammatory activity in arthritic rats, and the addition of AA increased proteoglycan density, but did not affect cytokine expression.
35328687 Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis 2022 Mar 17 Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine-glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine-glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.
35224383 Unraveling the Molecular Mechanism of Recognition of Selected Next-Generation Antirheumato 2022 Feb 22 Rheumatoid arthritis (RA) is a chronic immune-related condition, primarily of joints, and is highly disabling and painful. The inhibition of Janus kinase (JAK)-related cytokine signaling pathways using small molecules is prevalent nowadays. The JAK family belongs to nonreceptor cytoplasmic protein tyrosine kinases (PTKs), including JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase 2). JAK1 has received significant attention after being identified as a promising target for developing anti-RA therapeutics. Currently, no crystal structure is available for JAK1 in complex with the next-generation anti-RA drugs. In the current study, we investigated the mechanism of binding of baricitinib, filgotinib, itacitinib, and upadacitinib to JAK1 using a combined method of molecular docking, molecular dynamics simulation, and binding free energy calculation via the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) scheme. We found that the calculated binding affinity decreases in the order upadacitinib > itacitinib > filgotinib > baricitinib. Due to the increased favorable intermolecular electrostatic contribution, upadacitinib is more selective to JAK1 compared to the other three inhibitors. The cross-correlation and principal component analyses showed that different inhibitor bindings significantly affect the binding site dynamics of JAK1. Furthermore, our studies indicated that the hydrophobic residues and hydrogen bonds from the hinge region (Glu(957) and Leu(959)) of JAK1 played an essential role in stabilizing the inhibitors. Protein structural network analysis reveals that the total number of links and hubs in JAK1/baricitinib (354, 48) is more significant than those in apo (328, 40) and the other three complexes. The JAK1/baricitinib complex shows the highest probability of the highest-ranked community, indicating a compact network of the JAK1/baricitinib complex, consistent with its higher stability than the rest of the four systems. Overall, our study may be crucial for the rational design of JAK1-selective inhibitors with better affinity.
35532799 [Therapeutic effects of complex multimodal rheumatologic treatment in the Rheumatology Cen 2022 May 9 INTRODUCTION: The concept of complex multimodal rheumatologic treatment (CMRT) has been established for several years in German rheumatologic departments and aims at a multifaceted therapeutic approach to patients with rheumatic diseases. Objective of this study was to examine the therapeutic effect of CMRT in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in an acute rheumatology center. METHODS: The treatment success of CMRT was evaluated by epidemiologic data, patient questionnaires on visual analog scales (VAS) regarding morning stiffness, pain and disease activity (DA), as well as clinical scores (Disease Activity Score 28 [DAS28], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI]), laboratory inflammation markers (CRP, erythrocyte sedimentation rate) and medication in three visits: visit 1 = begin of CMRT; visit 2 = end of CMRT; visit 3 = 3 months after CMRT. RESULTS: In this study 162 patients from the Rheumatology Center, Rhineland-Palatinate, Germany (96 (59.3%) RA, 30 (18.8%) AS, 36 (22.2%) PsA) were recruited. Statistical examinations revealed a significant improvement of VAS(DA) (visit 2 versus visit 1: RA: p = 0.02, AS: p < 0.001, PsA: p < 0.001), morning stiffness (RA: p < 0.001, AS: p = 0.03, PsA: p < 0.001) and patient reported pain (all; p < 0.001) in the context of CMRT. In the RA and AS subgroups improvements of DAS28 and BASDAI could also be observed (visit 2 versus visit 1: both; p < 0.001). Moreover, significant improvement of patient reported outcomes could be observed 3 months after CMRT regarding VAS(DA) (RA: p = 0.02 und AS: p = 0.03, morning stiffness (PsA: p = 0.02) and patient reported pain (RA: p = 0.01)). Interestingly, subgroup analyses showed that the therapeutic benefit was independent of the concomitant pharmacotherapy. CONCLUSION: The results of this study suggest a therapeutic benefit for patients being treated by CMRT and highlight the high value of this therapeutic concept in patients with systemic-inflammatory rheumatic diseases.
35392426 Using patient-reported data from a smartphone app to capture and characterize real-time pa 2022 OBJECTIVE: We aimed to explore the frequency of self-reported flares and their association with preceding symptoms collected through a smartphone app by people with RA. METHODS: We used data from the Remote Monitoring of RA study, in which patients tracked their daily symptoms and weekly flares on an app. We summarized the number of self-reported flare weeks. For each week preceding a flare question, we calculated three summary features for daily symptoms: mean, variability and slope. Mixed effects logistic regression models quantified associations between flare weeks and symptom summary features. Pain was used as an example symptom for multivariate modelling. RESULTS: Twenty patients tracked their symptoms for a median of 81 days (interquartile range 80, 82). Fifteen of 20 participants reported at least one flare week, adding up to 54 flare weeks out of 198 participant weeks in total. Univariate mixed effects models showed that higher mean and steeper upward slopes in symptom scores in the week preceding the flare increased the likelihood of flare occurrence, but the association with variability was less strong. Multivariate modelling showed that for pain, mean scores and variability were associated with higher odds of flare, with odds ratios 1.83 (95% CI, 1.15, 2.97) and 3.12 (95% CI, 1.07, 9.13), respectively. CONCLUSION: Our study suggests that patient-reported flares are common and are associated with higher daily RA symptom scores in the preceding week. Enabling patients to collect daily symptom data on their smartphones might, ultimately, facilitate prediction and more timely management of imminent flares.
35087267 Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models. 2022 Indeed, the body articulation units, commonly referred to as body joints, play significant roles in the musculoskeletal system, enabling body flexibility. Nevertheless, these articulation units suffer from several pathological conditions, such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, gout, and psoriatic arthritis. There exist several treatment modalities based on the utilization of anti-inflammatory and analgesic drugs, which can reduce or control the pathophysiological symptoms. Despite the success, these treatment modalities suffer from major shortcomings of enormous cost and poor recovery, limiting their applicability and requiring promising strategies. To address these limitations, several engineering strategies have been emerged as promising solutions in fabricating the body articulation as unit models towards local articulation repair for tissue regeneration and high-throughput screening for drug development. In this article, we present challenges related to the selection of biomaterials (natural and synthetic sources), construction of 3D articulation models (scaffold-free, scaffold-based, and organ-on-a-chip), architectural designs (microfluidics, bioprinting, electrospinning, and biomineralization), and the type of culture conditions (growth factors and active peptides). Then, we emphasize the applicability of these articulation units for emerging biomedical applications of drug screening and tissue repair/regeneration. In conclusion, we put forward the challenges and difficulties for the further clinical application of the in vitro 3D articulation unit models in terms of the long-term high activity of the models.
35280915 Cardiovascular Risks and Risk Stratification in Inflammatory Joint Diseases: A Cross-Secti 2022 BACKGROUND: It is well established that patients with inflammatory joint diseases (IJD) have an increased cardiovascular (CV) mortality and morbidity. According to the 2016 EULAR recommendations on CV risk management, rheumatologists should ensure appropriate management of CV risk in rheumatoid arthritis (RA) and other IJDs. The aim was to assess the CV risk and CV disease in Middle-European patients with IJD. METHODS: A retrospective chart review was performed for CV risk factors and CV disease in outpatients of a rheumatology outpatient clinic. CV risk was assessed according to the 2016 European Guidelines on CV disease prevention and also using 2 other approaches to compare the results with data from Norwegian and Spanish cohorts. RESULTS: Out of 432 patients, the prevalence of CV disease reached from 8.7% in spondyloarthritis (SpA) and 12.8% in psoriatic arthritis (PsA) to 18.7% in patients with RA. The number of CV risk factors did not differ between patients with RA, SpA, PsA, and non-inflammatory rheumatic disease (NIRD) (with 1.68 ± 0.13, 1.70 ± 0.13, 2.04 ± 0.16, and 1.78 ± 0.34, respectively). CV risk assessment could be performed in 82 patients after exclusion because of missing data and age. Stratification according to ESC guidelines showed low in 50%, moderate in 12.2%, high in 20.7%, and very high CV risk in 17.1% of patients aged between 40 and 65 years. CV risk in the Middle-European patients with IJD was higher than in the German general population (p = 0.004), and similar to the Norwegian patients with IJD, although patients with Middle-European PsA were at higher risk than the Norwegian patients (p = 0.045). Compared to the Spanish patients, Middle-European patients with IJD were more likely assigned to the high- to a very high-risk group (34.2 vs. 16.2%, p < 0.001), especially in RA disease (49.1 vs. 21%, respectively, p < 0.001). DISCUSSION: High prevalence of established CV disease together with high CV risk in patients with IJD urges for increased vigilance for CV risk factors followed by appropriate interaction by the treating physicians. The prospective use of an international CV risk assessment tool will allow not only estimation of the individual CV risk but also provide data for direct comparisons with the general population and other international cohorts.
35644324 Association between biologic therapy and fracture incidence in patients with selected rheu 2022 May 26 OBJECTIVES: To investigate the effect of biologic therapy on risk of fracture in selected rheumatic and autoimmune diseases. METHODS: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to June 4, 2021. Randomized clinical trials (RCTs) comparing biological disease-modifying antirheumatic drugs (bDMARDs) with non-bDMARDs or placebo in patients with five selected rheumatic and autoimmune diseases were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95 % confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture. RESULTS: A total of 100 RCTs involving 51,413 participants fulfilled the inclusion criteria. In patients with psoriasis (Ps), and psoriatic arthritis (PsA), compared with placebo or non-bDMARDs therapy, the risk of major osteoporotic fracture (OR, 0.34 [95 %Cl, 0.15-0.76], p = 0.009), hip fracture (OR, 0.22 [95 %Cl, 0.05-0.89], p = 0.03), and osteoporotic non-vertebral fracture (OR, 0.26 [95 %Cl, 0.10-0.62], p = 0.003) were significantly decreased with the use of bDMARDs. In patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), systemic lupus erythematosus (SLE), and inflammatory bowel diseases (IBD), the risk of fracture were not changed with biologic treatment. CONCLUSIONS: The existing evidence from RCTs indicated the use of bDMARDs was associated with a low risk of major osteoporotic fracture, hip fracture, and osteoporotic non-vertebral fracture in patients with Ps and PsA. There are still urgent needs for studies regarding the actions of biologic therapies on the risk of bone fractures in systemic inflammatory diseases.
35077020 Examining Health Outcomes in Juvenile Idiopathic Arthritis: A Genetic Epidemiology Study. 2022 Apr OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease; however, little is known about its wider health impacts. This study explores health outcomes associated with JIA genetic liability. METHODS: We used publicly available genetic data sets to interrogate the genetic correlation between JIA and 832 other health-related traits using linkage disequilibrium score regression. Two-sample Mendelian randomization (2SMR) was used to examine four genetic correlates for evidence of causality. RESULTS: We found robust evidence (adjusted P [P(adj) ] < 0.05) of genetic correlation between JIA and rheumatoid arthritis (genetic correlation [r(g) ] = 0.63, P(adj)  = 0.029), hypothyroidism/myxedema (r(g)  = 0.61, P(adj)  = 0.041), celiac disease (CD) (r(g)  = 0.58, P(adj)  = 0.032), systemic lupus erythematosus (r(g)  = 0.40, P(adj)  = 0.032), coronary artery disease (CAD) (r(g)  = 0.42, P(adj)  = 0.006), number of noncancer illnesses (r(g)  = 0.42, P(adj)  = 0.016), paternal health (r(g)  = 0.57, P(adj)  = 0.032), and strenuous sports (r(g)  = -0.52, P(adj)  = 0.032). 2SMR analyses found robust evidence that genetic liability to JIA was causally associated with the number of noncancer illnesses reported by UK Biobank (UKBB) participants (increase of 0.03 noncancer illnesses per doubling odds of JIA, 95% confidence interval 0.01-0.05). CONCLUSION: This study illustrates genetic sharing between JIA and a diversity of health outcomes. The causal association between genetic liability to JIA and noncancer illnesses suggests a need for broader health assessments of patients with JIA to reduce their potential comorbid burden. The strength of genetic correlation with hypothyroidism and CD implies that patients with JIA may benefit from CD and thyroid function screening. Strong positive genetic correlation between JIA and CAD supports the need for cardiovascular risk assessment and risk factor modification.
35583934 A Risk Score to Detect Subclinical Rheumatoid Arthritis-Associated Interstitial Lung Disea 2022 May 18 OBJECTIVES: Patients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms thanks to chest high-resolution computed tomography (HRCT) scan screening. Our objective was to develop and validate a risk score for subclinical RA-ILD. METHODS: A discovery and a replication population constituted of patients without pulmonary symptoms from 2 prospective RA cohorts (ESPOIR and TRANSLATE2) who underwent chest HRCT scans. All patients were genotyped for MUC5B rs35705950. After multiple logistic regression, a risk score based on independent risk factors for subclinical RA-ILD was developed in the discovery population and tested for validation in the replication population. RESULTS: Discovery and replication populations included 163 and 89 patients, respectively. The prevalence of subclinical RA-ILD was 19.0% and 16.9%, respectively. In the discovery population, independent risk factors for subclinical RA-ILD were the MUC5B rs35705950 T risk allele (odds ratio [OR]=3.74; 95% confidence interval [CI] [1.37-10.39], male sex (OR=3.93; 95%CI [1.40-11.39]), older age at RA onset (for each year, OR=1.10; 95%CI [1.04-1.16]) and increased mean DAS28-ESR (for each unit, OR=2.03; 95%CI [1.24-3.42]). We developed and validated a derived risk score with AUC=0.82; 95%CI [0.70-0.94] and 0.78; 95%CI [0.65-0.92], respectively. Excluding MUC5B rs35705950 from the model provided a lower goodness of fit (likelihood ratio test, P=0.01). CONCLUSIONS: We developed and validated a risk score that could help identifying patients at high-risk for subclinical RA-ILD. Our findings support an important contribution of MUC5B rs35705950 to subclinical RA-ILD risk.
35428723 Whole-Body Macrophage Positron Emission Tomography Imaging for Disease Activity Assessment 2022 Apr 15 OBJECTIVE: To investigate the potential of whole-body positron emission tomography/computed tomography (PET/CT) with a macrophage tracer to image arthritis in patients with early rheumatoid arthritis (RA). METHODS: Thirty-five previously untreated, clinically active patients with early RA underwent whole-body PET/CT scanning with the macrophage tracer (R)-[(11)C]PK11195 in addition to clinical assessment (Disease Activity Score in 44 joints [DAS44]). Tracer uptake was assessed quantitatively as standardized uptake values (SUVs). In addition, 2 readers blinded to clinical assessment visually scored tracer uptake in joints. Clinical and PET variables were compared using Cohen κ, linear regression/correlation, and t tests, where appropriate. RESULTS: All but 1 patient showed enhanced tracer uptake in at least 1 joint. Twelve percent of all joints (171/1470) were visually positive on the PET scan, most frequently the small joints in feet (40%) and hands (37%), followed by wrists (15%). Correlations of visual scores with clinical findings both at patient and joint levels were absent or weak. In contrast, average SUVs in the hands, feet, and whole body showed significant correlations with DAS44 scores, with the best correlation seen in the feet (R (2) = 0.29, P < 0.01). CONCLUSION: Clinically active patients with early RA had increased joint uptake of a macrophage PET tracer, especially in the feet. Quantitative, but not visual PET measures of whole body and joint groups, particularly the feet, showed moderate and statistically significant correlations with clinical outcome.
35027398 Accounting for missing data caused by drug cessation in observational comparative effectiv 2022 May OBJECTIVES: To assess the performance of statistical methods used to compare the effectiveness between drugs in an observational setting in the presence of attrition. METHODS: In this simulation study, we compared the estimations of low disease activity (LDA) at 1 year produced by complete case analysis (CC), last observation carried forward (LOCF), LUNDEX, non-responder imputation (NRI), inverse probability weighting (IPW) and multiple imputations of the outcome. All methods were adjusted for confounders. The reasons to stop the treatments were included in the multiple imputation method (confounder-adjusted response rate with attrition correction, CARRAC) and were either included (IPW2) or not (IPW1) in the IPW method. A realistic simulation data set was generated from a real-world data collection. The amount of missing data caused by attrition and its dependence on the 'true' value of the data missing were varied to assess the robustness of each method to these changes. RESULTS: LUNDEX and NRI strongly underestimated the absolute LDA difference between two treatments, and their estimates were highly sensitive to the amount of attrition. IPW1 and CC overestimated the absolute LDA difference between the two treatments and the overestimation increased with increasing attrition or when missingness depended on disease activity at 1 year. IPW2 and CARRAC produced unbiased estimations, but IPW2 had a greater sensitivity to the missing pattern of data and the amount of attrition than CARRAC. CONCLUSIONS: Only multiple imputation and IPW2, which considered both confounding and treatment cessation reasons, produced accurate comparative effectiveness estimates.
34714156 The Relationship Between Autoimmune Disease and Disease-Modifying Antirheumatic Drugs on W 2022 Feb 3 Objective: To evaluate the role of disease-modifying antirheumatic drugs (DMARDs) on wound healing outcomes of patients with autoimmune disease at our tertiary wound care center. Approach: Retrospective review of patients presenting to our wound care center between 2014 and 2018 with both chronic wounds and a history of inflammatory disease. Patient demographics, comorbid conditions, and progression to complete wound healing were compared between those taking DMARDs or not at the time of wound onset. The study adheres to the STROBE statement. Results: Fifty-eight patients with a total of 296 wounds were retrospectively reviewed. Patients were taking at least one DMARD at wound onset in 217 (73.3%) of these wounds. The average number of DMARDs at wound onset was 1.5 (standard deviation 1.2). Two hundred ten wounds progressed to heal (70.9%), with a median time to healing of 229.5 days (interquartile range 71.0-490.0). Of the 210 wounds that healed, patients taking at least one DMARD had a significantly shorter time to healing relative to patients who were not on any DMARDs (median 190.5 days vs. 340.0 days, p = 0.0156). Innovation: Characterizing wound healing outcomes at a tertiary hospital with a dedicated wound care center and analyzing the role of DMARDs in wound healing progression. Conclusions: The median time to healing in the studied cohort was 229.5 days, which is much longer than the healing time for noninfected diabetic foot ulcers at our institution. These findings highlight the wound healing challenges posed by underlying autoimmune disease.(10).
35172995 Influence of information provided prior to switching from Humira to biosimilar adalimumab 2022 Feb 16 OBJECTIVES: To investigate the perceptions and experiences of people with specific immune-mediated inflammatory diseases during the process of switching from Humira to biosimilar adalimumab. DESIGN: Cross-sectional survey. SETTING: An anonymised, self-administered, web-based survey. PARTICIPANTS: The participants were drawn from members and non-members of either the National Rheumatoid Arthritis Society, the National Axial Spondyloarthritis Society, Crohn's and Colitis UK, or Psoriasis Association. Birdshot Uveitis Society and Olivia's Vision also signposted to the survey links. RESULTS: A total of 899 people living with various immune mediated inflammatory diseases participated in this survey. Thirty-four per cent of respondents reported poor overall satisfaction with their biosimilar adalimumab after the switch, associated with complaints related to the switching process including lack of shared decision making, scarcity of information provided by or signposted to by the department instigating the switch as well as lack of training with the new injection device. Where training with the new device had been provided, there were significantly reduced reports of pain when injecting the new biosimilar (OR 0.20, 95% CI 0.07 to 0.55), side effects (OR 0.17, 95% CI 0.06 to 0.47) and difficulty in using the new injection device (OR 0.25, 95% CI 0.15 to 0.41). Self-reported side effects were reduced by (OR 0.13, 95% CI 0.05 to 0.38) when written information was provided by healthcare professionals and by (OR 0.15, 95% CI 0.05 to 0.42) with provision of verbal information. Difficulty in using the new injection device was also reduced by provision of satisfactory information such as written documents (OR 0.38, 95% CI 0.23 to 0.63) or by verbal communication with healthcare professionals (OR 0.45, 95% CI 0.27 to 0.73). Finally, provision of satisfactory written or verbal information was associated with a reduction in any negative perception regarding symptom control with the new biosimilar by (OR 0.05, 95% CI 0.004 to 0.57) and by (OR 0.15, 95% CI 0.03 to 0.84), respectively. CONCLUSIONS: Patient reported experiences of the process of switching from originator to biosimilar emphasise the importance of clear communication, training and information in order to optimise perception and maximise achievable outcomes with the new treatment.
34470798 COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatol 2022 Jan OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1β, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.
35372645 Effects of oral losartan administration on homeostasis of articular cartilage and bone in 2022 Jun BACKGROUND AND AIMS: Previous work has shown that oral losartan can enhance microfracture-mediated cartilage repair in a rabbit osteochondral defect injury model. In this study, we aimed to determine whether oral losartan would have a detrimental effect on articular cartilage and bone homeostasis in the uninjured sides. METHODS: New Zealand rabbits were divided into 4 groups including normal uninjured (Normal), contralateral uninjured side of osteochondral defect (Defect), osteochondral defect plus microfracture (Microfracture) and osteochondral defect plus microfracture and losartan oral administration (10 mg/kg/day) (Losartan). Rabbits underwent different surgeries and treatment and were sacrificed at 12 weeks. Both side of the normal group and uninjured side of treatment groups tibias were harvested for Micro-CT and histological analysis for cartilage and bone including H&E staining, Herovici's staining (bone and cartilage) Alcian blue and Safranin O staining (cartilage) as well as immunohistochemistry of losartan related signaling pathways molecules for both cartilage and bone. RESULTS: Our results showed losartan oral treatment at 10 mg/kg/day slightly increase Alcian blue positive matrix as well as decrease collagen type 3 in articular cartilage while having no significant effect on articular cartilage structure, cellularity, and other matrix. Losartan treatment also did not affect angiotensin receptor type 1 (AGTR1), angiotensin receptor type 2 (AGTR2) and phosphorylated transforming factor β1 activated kinase 1 (pTAK1) expression level and pattern in the articular cartilage. Furthermore, losartan treatment did not affect microarchitecture of normal cancellous bone and cortical bone of tibias compared to normal and other groups. Losartan treatment slightly increased osteocalcin positive osteoblasts on the surface of cancellous bone and did not affect bone matrix collagen type 1 content and did not change AGTR1, AGTR2 and pTAK1 signal molecule expression. CONCLUSION: Oral losartan used as a microfracture augmentation therapeutic does not have significant effect on uninjured articular cartilage and bone based on our preclinical rabbit model. These results provided further evidence that the current regimen of using losartan as a microfracture augmentation therapeutic is safe with respect to bone and cartilage homeostasis and support clinical trials for its application in human cartilage repair.
35369853 Comparison of complications during 1-year follow-up between remitting seronegative symmetr 2022 Apr 2 Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE), a rheumatic disease affecting the elderly, responds well to corticosteroids; however, our RS3PE patients' corticosteroid therapy is longer than expected. Elderly-onset rheumatoid arthritis (EORA) patients are reported to be at a significantly increased risk for steroid-related side effects including cardiovascular diseases (CVDs). To clarify the complications during a 1-year follow-up in corticosteroid-treated RS3PE patients compared to EORA patients. We retrospectively analyzed the records of 47 RS3PE patients (28 men, 19 women, age 78.4 ± 7.5 years) and 46 EORA patients (10 men, 36 women; 77.0 ± 6.8 yrs) to compare the complications over a 1-year follow-up. The RS3PE and EORA groups' average initial PSL doses were 16.5 ± 7.2 mg/day and 7.3 ± 4.6 mg/day, respectively. During the 1-year follow-up after treatment, there was no significant increase in CVDs in both groups. However, infections occurred in nine RS3PE patients, which is a significantly higher incidence compared to the EORA patients with infections (n = 3). The initial PSL dose was the independent variable associated with the incidence of infection. Infections were significantly increased during elderly RS3PE patients' steroid therapy. The initial corticosteroid dose was an infection-risk factor.Key messagesInfections are increased during steroid therapy in elderly patients with RS3PE syndrome.The initial dose of corticosteroids was one of the risk factors for infections.
35079870 Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances 2022 Jan 25 Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.
35062304 Does HTLV-1 Infection Show Phenotypes Found in Sjögren's Syndrome? 2022 Jan 6 Viruses are a possible cause for Sjögren's syndrome (SS) as an environmental factor related to SS onset, which exhibits exocrine gland dysfunction and the emergence of autoantibodies. Although retroviruses may exhibit lymphocytic infiltration into exocrine glands, human T-cell leukemia virus type 1 (HTLV-1) has been postulated to be a causative agent for SS. Transgenic mice with HTLV-1 genes showed sialadenitis resembling SS, but their phenotypic symptoms differed based on the adopted region of HTLV-1 genes. The dominance of tax gene differed in labial salivary glands (LSGs) of SS patients with HTLV 1-associated myelopathy (HAM) and adult T-cell leukemia. Although HTLV-1 was transmitted to salivary gland epithelial cells (SGECs) by a biofilm-like structure, no viral synapse formation was observed. After infection to SGECs derived from SS patients, adhesion molecules and migration factors were time-dependently released from infected SGECs. The frequency of the appearance of autoantibodies including anti-Ro/SS-A, La/SS-B antibodies in SS patients complicated with HAM is unknown; the observation of less frequent ectopic germinal center formation in HTLV-1-seropositive SS patients was a breakthrough. In addition, HTLV-1 infected cells inhibited B-lymphocyte activating factor or C-X-C motif chemokine 13 through direct contact with established follicular dendritic cell-like cells. These findings show that HTLV-1 is directly involved in the pathogenesis of SS.