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ID PMID Title PublicationDate abstract
34755028 The perception of stakeholders on the applicability of nurse-led clinics in the management 2021 Nov OBJECTIVES: RA should be treated to target in a process of shared decision-making with patients. Person-centred care is essential to meeting specific patient needs. Nurse-led clinics, where a nurse is responsible for care, have demonstrated added value in some countries but are still not implemented widely. This study aimed to explore stakeholders' perceptions of advantages, disadvantages and conditions for the implementation of nurse-led clinics for RA in Belgium. METHODS: We performed a cross-sectional qualitative study consisting of five semi-structured focus group interviews. Rheumatology nurses, patients with RA and rheumatologists were interviewed as stakeholders. The analysis was carried out by three researchers according to the Qualitative Analysis Guide of Leuven (QUAGOL), formulating a conceptual framework of overarching themes and deconstructing this into perceived advantages, disadvantages and conditions. RESULTS: Two focus groups with nurses (total n = 16), two with patients (n = 17) and one with rheumatologists (n = 9) were conducted. The interview synthesis resulted in five overarching themes across stakeholders: efficiency of care, disease management, legal and organizational requirements, the conventional role of the nurse and the extended role of the nurse. All stakeholders perceived additional education for nurses as essential, but rheumatologists debated nurses' abilities to lead a rheumatology clinic. Furthermore, patients preferred care protocols to guide nurses, and care providers approached this reluctantly. Generally, patients with a well-controlled disease were perceived as the ideal candidates for nurse-led care. CONCLUSION: Nurse-led clinics could provide many benefits but require additional nurse education and a legal and organizational framework before being implemented widely and successfully.
34386703 Development of an Educational Video for Self-Assessment of Patients with RA: Steps, Challe 2021 Mar OBJECTIVES: The primary objective was to develop an educational video to teach patients with rheumatoid arthritis (RA) self-assessment of their disease activity. Secondary objectives were to validate the video, identify the challenges in producing it, and the responses to these challenges. METHODS: Rheumatologists from 7 Middle Eastern Arab countries (MEAC) discussed unmet needs in the education of patients with RA. They reviewed pre-existing educational audiovisual material and drafted the script for a new video in Arabic. The video was produced in collaboration with a technical team, then validated by patients using a standardized interview. At each step of production, challenges were identified. RESULTS: Twenty-three rheumatologists from MEAC identified unmet needs in patients' education. A video was produced, explaining the concepts of treat-to-target and showing a patient performing self-assessment using DAS-28. Sixty-two patients were interviewed for validation and found the video to be useful and easy to understand, albeit not replacing the physician's visit. Most common challenges encountered included acceptance of patient empowerment, agreement on DAS-28 as composite measure, production of a comprehensible written Arabic text, and addressing the population cultural mix. CONCLUSION: Despite challenges, the video was well accepted among patients and can be used for clinical and research purposes. It is particularly useful in pandemic periods where social distancing is recommended.
33811317 Probabilistic Linkage of Randomized Controlled Trial Data to Administrative Claims: A Case 2021 Jun INTRODUCTION: The aim of this work is to assess the feasibility of probabilistically linking randomized controlled trial (RCT) data to claims data in a real-world setting to inform future rheumatoid arthritis (RA) research. METHODS: This retrospective cohort study utilized IQVIA's Patient Centric Medical Claims (Dx) Database, IQVIA's Longitudinal Prescription Claims (LRx) Database, and Lilly's baricitinib RCT data from a sample of patients that consented to the linkage of their de-identified insurance claims to their de-identified RCT data. Patients were initially matched on age, gender, and three-digit ZIP code of the provider and further matched according to a point scoring system using additional clinical variables. RESULTS: A total of 245 patients from 49 US clinical trial sites were eligible for the study and 78 (31.8%) of these patients consented to participate. Of the 78 consented patients, 69 (88%) were successfully matched on age, gender, and three-digit ZIP code of the provider. Of the 69 patients successfully matched on age, gender, and three-digit ZIP code of the provider, 44 (63.8%) had at least one sufficient match using the point scoring system. Of these 44, 23 (52.3%) patients matched at a ratio of one RCT patient to one Dx/LRx patient, 11 (25.0%) at a ratio of 1:2, 7 (15.9%) at a ratio of 1:3 and three (6.8%) at a ratio of 1:4 or greater. To further improve match ratios, a variable hierarchy was applied to the 18 RCT patients with 2-3 matches. Overall, 38 of the 78 (48.7%) consented RCT patients were successfully matched 1:1 to claims database patients. CONCLUSIONS: This probabilistic linkage methodology demonstrates the feasibility, at a moderate linkage rate, of linking patients from RCTs to real-world data, which can provide a means to assess additional information not usually collected within or following a clinical trial.
33693304 Utility of the HandScan in monitoring disease activity and prediction of clinical response 2021 OBJECTIVES: The aims were to determine the ability of the HandScan [assessing inflammation in hand and wrist joints using optical spectral transmission (OST)] to measure RA disease activity longitudinally, compared with DAS28, and to determine whether short-term (i.e. 1 month) changes in the OST score can predict treatment response at 3 or 6 months. METHODS: Participants visited the outpatient clinic before the start of (additional) RA medication and 1, 3 and 6 months thereafter. Disease activity was monitored at each visit with the HandScan and DAS28 in parallel. A mixed effects model with DAS28 as the outcome variable with a random intercept at patient level, visit month and DAS28 one visit earlier was used to evaluate whether changes in the OST score are related to changes in DAS28. Binary logistic regression was used to test the predictive value of short-term changes in the OST score together with the baseline OST score for achievement of treatment response (EULAR or ACR criteria). All models were adjusted for RA stage (early or established). RESULTS: In total, 64 RA patients were included. One unit change in OST score was found to be related to an average DAS28 change of 0.03 (95% CI: 0.01, 0.06, P = 0.03). When adding OST score as a variable in the longitudinal model, the ability of the model to estimate DAS28 (i.e. explained variance) increased by 2%, to 59%. Neither baseline OST score nor short-term change in OST score was predictive for treatment response at 3 or 6 months. CONCLUSION: A longitudinal association of OST score with DAS28 exists, although explained variance is low. The predictive ability of short-term changes in HandScan for treatment response is limited.
33505482 Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD 2021 Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.
33488026 Transcatheter Aortic Valve Implantation in Patients with Connective Tissue Disease. 2021 Jan BACKGROUND: There is still no consensus on the treatment of patients with connective tissue disease (CTD) with severe symptomatic aortic stenosis (AS). The aim of this study was to evaluate the feasibility and safety of transcatheter aortic valve implantation (TAVI) in patients with CTD. METHODS: Five hundred and fifty consecutive symptomatic severe AS patients who underwent TAVI between 2011 and 2019 were included in this retrospective study, of whom 14 had CTD. Follow-up was performed 30 days, 6 months, and 1 year after the procedure. RESULTS: Of the 14 (2.5%) patients who had CTD, most had rheumatoid arthritis (n = 10), followed by lupus erythematosus (n = 2), scleroderma (n = 1) and mixed (n = 1) CTD. The mean age was 77.6 ± 7.9 years, and there was no statistical difference between the CTD and no-CTD groups. In addition, significantly more of the CTD patients (85.7%) were female compared to the no-CTD group (p = 0.018). None of the patients in the CTD group had acute kidney injury, stroke, major bleeding, or pericardial effusion. However, significantly more patients in the CTD group (n = 4) needed permanent pacemaker implantation than in the no-CTD group (p = 0.008). There were no significant differences between the two groups in terms of mean discharge time (CTD 4.6 ± 2.0, no-CTD 4.5 ± 2.3 days, p = 0.926) and in-hospital mortality [CTD 1 (7.1%), no-CTD 21 (3.9%); p = 0.542]. CONCLUSIONS: In this study, we presented the results of TAVI in patients with and without CTD. The TAVI procedure had similar mid-term outcomes in the two groups, and the CTD group had numerically lower rates of major complications at the cost of a higher incidence of pacemaker implantation.
33742643 Septic arthritis of temporomandibular joint. 2021 Mar Septic arthritis (SA) occurrence for temporomandibular joint (TMJ) is rare. Pain, fever, swelling or loss of TMJ function are the typical presentation. The more common diagnosis for these presentations is internal derangement, osteoarthritis and rheumatoid arthritis. Therefore, TMJ septic arthritis is a challenging diagnosis and at risk of delayed diagnosis. We present a case of TMJ septic arthritis in a 46 year old Malay female with underlying hypertension and hypercholestrolemia, which was diagnosed as internal derangement in the initial presentation. The initial radiograph was normal. Arthrocentesis procedure had temporarily relieved the symptoms before progressive facial swelling developed after a week. Contrast enhanced computed tomography (CECT) brain revealed left TMJ abscess formation with left condylar erosion. Patient subsequently improved after wound debridement, left condylectomy and antimicrobial therapy.
34535818 [State of the art: fertility and pregnancy in rheumatic diseases]. 2021 Oct Inflammatory rheumatic diseases often affect women of childbearing age, for whom pregnancy is still associated with increased risks. At the same time, we are gaining more and more insights into risk factors and preventive strategies, enabling almost all women to have successful pregnancies with few adverse outcomes. The cornerstones are planning of the pregnancy under effective disease control and the modification of individual risk factors. Hydroxychloroquine is once again coming into focus as a compound with multiple positive effects. Recommendations published by the American College of Rheumatology (ACR) provide a practical overview of the evidence. Based on the current state of knowledge, rheumatologists can make a lasting contribution to a positive pregnancy outcome for mother and child.
33802091 Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases. 2021 Mar 10 Since 2015, 170 small molecules, 60 antibody-based entities, 12 peptides, and 15 gene- or cell-therapies have been approved by FDA for diverse disease indications. Recent advancement in medicine is facilitated by identification of new targets and mechanisms of actions, advancement in discovery and development platforms, and the emergence of novel technologies. Early disease detection, precision intervention, and personalized treatments have revolutionized patient care in the last decade. In this review, we provide a comprehensive overview of current and emerging therapeutic modalities developed in the recent years. We focus on nine diseases in three major therapeutics areas, diabetes, autoimmune, and neurological disorders. The pathogenesis of each disease at physiological and molecular levels is discussed and recently approved drugs as well as drugs in the clinic are presented.
35128325 Challenges in Applying Treat to Target Strategy in Sample of Iraqi Patients with Rheumatoi 2021 Dec OBJECTIVE: To identify barriers and factors that might hamper RA patients from achieving clinical target. PATIENTS AND METHODS: A total of 100 consecutive RA patients (95 females: 5 males) were included in this retrospective cross-sectional study. Data were collected at one point in time using questionnaire and interview. Demographic data, disease duration, functional classes, medications, and compliance assessment on the current treatments by using the Compliance Questionnaire Rheumatology (CQR19) were recorded for all patients. Achievement of clinical target was defined using the Clinical Disease Activity Index (CDAI; score ≤ 10). The main barriers preventing reaching the clinical target were reported for all the patients with moderate to high disease activity. RESULTS: Among 100 patients with a recorded CDAI, 58 patients (58%) had not achieved the clinical target (CDAI > 10), for whom the barriers to disease control were recorded. The recorded barriers were drug unavailability/interruption (34.5%), under-treatment (20.7%), insufficient time to assess treatment response to recently initiated DMARDs (12.1%), non- inflammatory musculoskeletal pain (10.3%), had no further drug option available (10.3%), irreversible joint damage (5.2%), and other or non- identified barriers (6.9%). All patients completed CQR-19 items and poor compliance was identified as a predictor of high disease activity (P=0.001). Disease duration had a strong effect on the likelihood of patient response (P=0.035). There was a lower response rate among current smokers (P=0.007). Additionally, functional impairment appeared to be associated with high disease activity (P=0.0001). A significantly larger portion of low disease activity patients were presently on biological treatments (P=0.037) while steroid use had been associated with high disease activity (P=0.03). Age, gender, and Body Mass Index did not predict response to treatment. CONCLUSIONS: This study identified interruption of biologic drugs supply as a large barrier to RA treatment target. The data supported improved outcomes among patients receiving biological treatments. Additionally, certain factors were associated with high disease activity including longer disease duration, functional impairment, smoking, non-adherence, and steroid use.
34682981 Can Studying Genetically Predisposed Individuals Inform Prevention Strategies for RA? 2021 Sep 29 Rheumatoid arthritis (RA) is a prevalent autoimmune disorder in which complex genetic predisposition interacts with multiple environmental factors to precipitate chronic and progressive immune-mediated joint inflammation. Currently, in most affected individuals, ongoing suppression of the inflammation is required to prevent irreversible damage and functional loss. The delineation of a protracted preclinical period in which autoimmunity is initially established and then evolves to become pathogenic provides unprecedented opportunities for interventions that have the potential to prevent the onset of this lifelong disease. Clinical trials aimed at assessing the impact of specific prevention strategies require the identification of individuals who are at high risk of future RA development. Currently, these risk factors include a strong family history of RA, and the detection of circulating RA-associated autoantibodies, particularly anti-citrullinated protein antibodies (ACPA). Yet, even in such individuals, there remains considerable uncertainty about the likelihood and the timeframe for future disease development. Thus, individuals who are approached to participate in such clinical trials are left weighing the risks and benefits of the prevention measures, while having large gaps in our current understanding. To address this challenge, we have undertaken longitudinal studies of the family members of Indigenous North American RA patients, this population being known to have a high prevalence of RA, early age of onset, and familial clustering of cases. Our studies have indicated that the concepts of "risk" and "prevention" need to be communicated in a culturally relevant manner, and proposed prevention interventions need to have an appropriate balance of effectiveness, safety, convenience, and cultural acceptability. We have focused our proposed prevention studies on immunomodulatory/anti-inflammatory nutritional supplements that appear to strike such a complex balance.
33658813 Changes in the Penetration Rate of Biosimilar Infliximab Within Japan Using a Japanese Cla 2021 PURPOSE: Infliximab, which was approved in 2002, had its first biosimilar launched in 2014 across Japan. However, the penetration rate of this biosimilar remains unclear given the limited data regarding its current clinical use throughout Japan. This study was conducted to describe the current clinical characteristics of patients receiving infliximab and the penetration rate of the reference infliximab and/or biosimilar infliximab using a Japanese administrative claims database. PATIENTS AND METHODS: This retrospective, descriptive study utilized the Japan Medical Data Vision database, a nationwide hospital-based database. Data on patients receiving infliximab recorded from April 2008 to March 2019 were extracted from the database. Patient characteristics of the reference and biosimilar infliximab groups and penetration rates according to fiscal year, target diseases diagnosis, and subsidy for intractable diseases were examined. RESULTS: A total of 9735 patients were extracted for analysis, among whom 92% (n=8950) and 8% (n=785) received only reference infliximab and its biosimilar, respectively. Both groups exhibited similar clinical characteristics. The biosimilar penetration rate increased from 0.8% in 2014 to 22.5% in 2018, with overall penetration rates throughout the period according to diagnosis (with or without subsidy) being 14.4% (with, 4.1%; without, 16.4%), 4.7% (with, 3.7%; without, 10.6%), 5.7% (with, 4.5%; without, 13.5%), and 7.5% (with, 4.4%; without, 8.2%) for rheumatoid arthritis, Crohn's disease, ulcerative colitis, and psoriasis, respectively. CONCLUSION: Biosimilar infliximab is prescribed for patients with similar characteristics to reference infliximab. Despite the increasing penetration rates according to target disease, they remain much lower among patients receiving subsidy for intractable disease than among those who do not.
34883243 Systematic assessment of the humoral response against SARS-CoV-2 in a French cohort of 283 2022 May OBJECTIVES: To estimate the seroprevalence of SARS-CoV-2 infection in patients with rheumatic diseases and to specify the proportion of asymptomatic and symptomatic forms of COVID-19. METHODS: We screened for SARS-CoV-2 infection among spondyloarthritis (SpA, n=143) or rheumatoid arthritis (RA, n=140) patients in our outpatient clinic at Cochin Hospital in Paris between June and August 2020. We performed a qualitative SARS-CoV-2 serological test which detects IgG directed against the N nucleocapsid protein (anti-N) and, for some patients, against the Spike protein (anti-S). Descriptive analyses were managed. RESULTS: During June-August 2020, the SARS-CoV-2 seroprevalence rate in our population was 2.83% (8/283 patients) without significant difference between RA and SpA patients (2.14% and 3.5%, respectively). We report 11 out of 283 patients (3.8%) with a diagnosis of SARS-CoV-2 infection. Among these 11 patients, 1 patient was asymptomatic (9%) with a confirmed diagnosis of COVID-19 by anti-S serology. Of the 283 patients, 85% were under bDMARDs, mainly on rituximab (RTX) (n=44) and infliximab (IFX) (n=136). CONCLUSIONS: The seroprevalence of SARS-CoV-2 in patients with rheumatic diseases, mainly under bDMARDs treatments, was 2.83%. Among infected patients, 9% were asymptomatic. Detecting SARS-CoV-2 infections could be based on the strategy using patients' interview and anti-N serology.
33919621 Long-Term Results of the Modular Physiological Wrist Prosthesis (MPW(®)) in Patients with 2021 Apr 18 The wrist is among the predilection sites of over 90% of cases of rheumatoid arthritis (RA). In advanced cases, total wrist arthroplasty (TWA) is an alternative to arthrodesis. The aim of this study is to present the long-term results of the modular physiological wrist prosthesis (MPW(®)) and to match them in context with the results of a standard population survey. In a retrospective study with follow-up, patients with an MPW(®) endoprosthesis were evaluated concerning the clinical and radiological outcome, complications were reviewed (incidence and type), and conversion to wrist fusion was assessed. Patient function measurements included the Mayo wrist score, the patient-specific wrist test, and therefore the DASH score (arm, shoulder, and hand). Thirty-four MPW(®) wrist prostheses were implanted in 32 patients, including thirty primary implantations and four changes of the type of the endoprosthesis. Sixteen patients (18 prostheses) underwent clinical and radiological follow-up. The average follow-up time was 8.5 years (1 to 16). Poor results of the MPW prosthesis are caused by the issues of balancing with luxation and increased PE wear. Salvage procedures included revision of the TWA or fusion. In successful cases, the flexion and extension movement averaged 40 degrees. The grip force was around 2.5 kg. The common DASH score was 79 points, with limited and problematic joints of the upper extremity. The MPW wrist prosthesis offered good pain relief and functional movement in over 80% of cases. The issues of dislocation and increased PE wear prevent better long-term results, as do the joints affected. A follow-up study with fittings under a contemporary anti-rheumatic therapy with biologicals suggests increasing score results. Type of study/level of evidence: Case series, IV.
33628645 Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets. 2021 BACKGROUND: "Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities (h (2)) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. METHODS: Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (β(FS), h (2) ={(1 + 8r(spouse)β(FS))(0.5) - 1}/(2r(spouse))) and offspring-parent regression slopes (β(OP), h (2) = 2β(OP)/(1 + r(spouse))) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. RESULTS: Quantile-specific h (2) (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted CRP distribution when estimated from β(OP) (P (trend) = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from β(FS) (P (trend) = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. CONCLUSION: Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF-α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.
33622154 Novel approaches to develop biomarkers predicting treatment responses to TNF-blockers. 2021 Apr Introduction: Chronic inflammatory diseases (CIDs) cause significant morbidity and are a considerable burden for the patients in terms of pain, impaired function, and diminished quality of life. Important progress in CID treatment has been obtained with biological therapies, such as tumor-necrosis-factor blockers. However, more than a third of the patients fail to respond to these inhibitors and are exposed to the side effects of treatment, without the benefits. Therefore, there is a strong interest in developing tools to predict response of patients to biologics. Areas covered: The authors searched PubMed for recent studies on biomarkers for disease assessment and prediction of therapeutic responses, focusing on the effect of TNF blockers on immune responses in spondyloarthritis (SpA), and other CID, in particular rheumatoid arthritis and inflammatory bowel disease. Conclusions will be drawn about the possible development of predictive biomarkers for response to treatment. Expert opinion: No validated biomarker is currently available to predict treatment response in CID. New insight could be generated through the development of new bioinformatic modeling approaches to combine multidimensional biomarkers that explain the different genetic, immunological and environmental determinants of therapeutic responses.
33400194 Patient Characteristics and Indicators of Treatment Initiation with Repository Corticotrop 2021 Mar Repository corticotropin injection (RCI) is indicated as adjunctive, short-term therapy in selected patients with RA. To characterize RCI users and identify predictors of RCI initiation in RA, we compared preindex characteristics, treatment patterns, comorbidities, healthcare resource utilization (HCRU), and costs for patients who had initiated RCI treatment (RCI cohort) versus patients with no RCI claims and ≥ 1 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD) claim (non-RCI ts/bDMARD cohort). We analyzed pharmacy and medical claims data from a large commercial and Medicare supplemental administrative database. Inclusion criteria were age ≥ 18 years, ≥ 1 inpatient or ≥ 2 outpatient claims with RA diagnosis (January 1, 2007-December 31, 2018), and 12-month continuous medical and pharmacy coverage preindex. Results from baseline cohort comparisons informed multiple logistic regression analysis. Compared with the non-RCI ts/bDMARD cohort (n = 162,065), the RCI cohort (n = 350) had a greater proportion of patients with higher Charlson comorbidity index (CCI) scores; higher mean claims-based index of RA severity and CCI scores; greater frequency of almost all comorbidities; higher use of nontraditional DMARDs, glucocorticoids, and opioids; higher all-cause HCRU; and higher medical and total costs. By multivariable analysis, the most significant predictors of RCI initiation were intermittent glucocorticoid use at any dose (odds ratio [OR] 1.67), extended-use glucocorticoids at medium (OR 2.03) and high doses (OR 2.99), nontraditional DMARD use (OR 2.09), anemia (OR 1.39), and renal disease (OR 2.45). Before RCI initiation, patients had more severe RA, higher comorbidity burden, greater use of glucocorticoids and opioids, and higher HCRU compared with non-RCI initiators. The most significant predictors for starting RCI in patients with RA were intermittent use of glucocorticoids at any dose, extended-use high-dose glucocorticoids, use of nontraditional DMARDs, and comorbid anemia and renal disease.
33368349 Systematic review of safety and efficacy of belimumab in treating immune-mediated disorder 2021 Sep BACKGROUND: Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell-activating factor (BAFF). OBJECTIVE: To evaluate belimumab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist guided the reporting of the data. We searched the PubMed database between October 4, 2016, and June 23, 2019, concentrating on immune-mediated disorders. RESULTS: The literature search identified 583 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 17 articles were finally included in a narrative synthesis. CONCLUSIONS: Belimumab is both safe and effective for the treatment of systemic lupus erythematosus. Results were further promising for the use of belimumab in patients with rheumatoid arthritis and Sjögren's syndrome. Conversely, results using belimumab in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and myasthenia gravis were rather disappointing.
34627365 sTNFRII-Fc modification protects human UC-MSCs against apoptosis/autophagy induced by TNF- 2021 Oct 9 BACKGROUND: Tumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their "homing" and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions. METHODS: Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence. RESULTS: sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α. CONCLUSION: sTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.
33484396 Umbelliferone Ameliorates Complete Freund Adjuvant-Induced Arthritis via Reduction of NF-Π2021 Aug Osteoclasts, bone-resorbing somatic cells, are directly responsible for bone destruction during rheumatoid arthritis. Complete Freund adjuvant (CFA) is a widely used animal model using rodents for studying rheumatoid arthritis (RA), which effectively manifests serious cartilage destruction and progressive bone erosion, affecting synovial joints and serious joint dysfunction. It was considered that joint injury in RA is induced through systemic inflammation pathway. Umbelliferone (UF), a coumarin derivative of Agele marmilosa, possesses anti-inflammatory activity. In the current study, we scrutinize the effect of umbelliferone on CFA-induced arthritis model and explore the possible mechanism on bone destruction. Intradermal administration of CFA (0.05 mL) was to induce RA manifestations in the experimental rats and the same oral administration of UF was received. The anti-arthritic activity of UF was determined by its inhibitory activity on various biochemical markers, viz., pro-inflammatory, inflammatory, antioxidant enzymes, and hematological parameters elevated during RA condition. We also estimated the mRNA expression of osteoclast parameters. Obtained result disclosed significant reduction in the paw edema and increment of the body weight after UF administration. UF reduce the inflammatory mediatory such as COX-2, PGE(2), NF-kB, and VEGF; pro-inflammatory cytokines include TNF-α, IL-1β, IL-6, IL-10, and IL-17 significantly. Moreover, UF treatment significantly reduced the osteoclast number via modulating the RANKL/RANK/OPG ratio. Furthermore, administration of umbelliferone significantly (P < 0.001) suppressed the NF-κB and VEGF. Collectively, our results indicated the novel role of umbelliferone in osteoclastogenesis and proved that umbelliferone is a modern therapeutic tool as a natural agent for treating arthritis and other autoimmune disorders with bone degradation.