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ID PMID Title PublicationDate abstract
32920169 Adjuvant-induced arthritis is a relevant model to mimic coronary and myocardial impairment 2021 Jan OBJECTIVES: To determine if the adjuvant-induced arthritis model reproduced coronary and cardiac impairments observed in rheumatoid arthritis patients. The link between disease activity and circulating levels of angiotensin II and endothelin-1 have been studied, as well as the myocardial susceptibility to ischemia. METHODS: At the acute inflammatory phase, coronary reactivity was assessed in isolated arteries, and cardiac function was studied in isolated perfused hearts, before and after global ischemia/reperfusion. Ischemic insult was evaluated by the infarct size, lactate dehydrogenase and creatine phosphokinase levels in coronary effluents. Cardiac myeloperoxidase activity was measured, as well as angiotensin II and endothelin-1 levels. RESULTS: Compared to controls, adjuvant-induced arthritis had reduced coronary Acetylcholine-induced relaxation associated with cardiac hypertrophy, both being correlated with plasma levels of endothelin-1 and angiotensin II, and arthritis score. Although cardiac function at baseline was similar from controls, adjuvant-induced arthritis rats exhibited lower cardiac functional recovery, increased myeloperoxidase activity, higher infarct size and creatine phosphokinase levels after ischemia/reperfusion. CONCLUSIONS: The adjuvant-induced arthritis model displays coronary endothelial dysfunction associated with myocardial hypertrophy and a reduced tolerance to ischemia. This model might be useful for deciphering the pathophysiology of cardiac dysfunction in rheumatoid arthritis and paves the way for studying the role of endothelin-1 and angiotensin II.
31566905 Do Patients With Moderate or High Disease Activity Escalate Rheumatoid Arthritis Therapy A 2020 Feb OBJECTIVE: Despite strong recommendations for routine measurement of rheumatoid arthritis (RA) disease activity and associated treatment changes to attain remission/low disease activity, the measurement tools that clinicians use to evaluate RA patients' disease activity and frequency of treatment change have not been well characterized. Therefore, we evaluated different measurement tools that physicians used to assess RA disease activity and associated RA treatment changes. METHODS: Using data from the Rheumatology Informatics System for Effectiveness (RISE) registry from January 2016 through June 2017, and using the following criteria: age ≥18 years, diagnosis of RA (International Classification of Diseases, Ninth and Tenth Revision, codes), ≥2 RISE visits, and ≥1 RA disease activity measure scored in 2016, we classified eligible patients' drug use at the index visit as monotherapy or combination therapy with conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (bDMARDs). Outcomes include change in treatment over 12 months. Mixed models identified factors associated with treatment change. RESULTS: Among 50,996 eligible patients, 27,274 had longitudinal data. The most commonly used measures were RAPID3 (78.9%) and the Clinical Disease Activity Index (CDAI) (34.2%). The frequency of treatment change during follow-up was relatively low (35.6-54.6%), even for patients with moderate/high disease activity according to RAPID3 or CDAI scores. Older patients (age ≥75 years; adjusted odds ratio [OR(adj) ] 0.63 [95% confidence interval (95% CI) 0.50-0.78]) and those already receiving combination therapy with csDMARDs (OR(adj) 0.45 [95% CI 0.33-0.61]) or combination therapy with bDMARDs (OR(adj) 0.30 [95% CI 0.24-0.38]) were less likely to change RA treatment even after multivariable adjustment. CONCLUSION: Using the American College of Rheumatology's national RISE registry, one- to two-thirds of RA patients failed to change their treatment, even when experiencing moderate/high disease activity. Multimodal interventions directed at both patients and providers are needed to encourage shared decision-making, goal-directed care, and to overcome barriers to treatment escalation.
32701780 Feasibility and Acceptability of a Self-Management Program for Patients With Rheumatoid Ar 2020 Jul/Aug BACKGROUND: Joint activity and protection are key components in the management of rheumatoid arthritis (RA). Despite a shift from care in health settings to empowering patients to play an active role in the day-to-day management of their own chronic conditions, there is little evidence on RA self-management, especially for Chinese patients. PURPOSE: This pilot study sought to determine the feasibility and acceptability of a self-management program for patients with RA in Taiwan. METHODS: Participants were recruited at a medical center in northern Taiwan. The intervention group participated in a 6-week self-management program; the control group received standard rheumatology care. Both groups underwent baseline assessments before the intervention and at 12 weeks. RESULTS: A total of 32 participants were recruited: 15 in the intervention group and 17 in the control group. Patients in the intervention group found the self-management protocol beneficial to their joint protection and activity behaviors and reported higher motivation to perform RA self-management. The posttest score for joint protection and activity self-management behavior were significantly greater for the intervention group than for the control group (p = .02). CONCLUSIONS: Participants in the intervention group were highly satisfied with home visits (which included peer story-telling and goal setting) and telephone calls to support their daily home-based joint protection and self-management activities (which included self-monitoring and self-evaluation). To mitigate the fear of scammers, researchers should begin by building a trust relationship with participants.
32116107 Up-regulated microRNA-411 or declined RIPK1 inhibits proliferation and promotes apoptosis 2020 Mar Rheumatoid arthritis (RA) is a chronic and inflammatory synovitis systemic disease. Due to the unknown pathogenesis, this study was to investigate the effect of microRNA (miR)-411 on apoptosis and joint function of synoviocytes in RA mice via RIPK1-mediated NF-κB signaling pathway. The collagen-induced arthritis model mice were induced via collagen type II and Freund's adjuvant. The mice were injected with miR-411 mimics, si-RIPK1 or miR-411 mimics + oe-RIPK1 to figure out their roles in cell apoptosis and inflammation of synovial tissues. Synoviocytes were grouped as in animal experiments. Proliferation and apoptosis of synoviocytes were detected upon treatment with overexpressed miR-411 and silenced RIPK1. The expression of miR-411, RIPK1 and NF-κB in synovial tissues and synoviocytes of RA mice was detected by RT-qPCR and Western blot analysis. Poorly expressed miR-411, and highly expressed NF-κB and RIPK1 existed in synovial tissue and synoviocytes of RA. Additionally, it was found that si-RIPK1 decreased NF-κB expression, and miR-411 mimics decreased both RIPK1 and NF-κB. MiR-411 had a targeted relationship with RIPK1. si-RIPK1 or miR-411 mimics promoted cell apoptosis and strained inflammation in synovial tissues of mice with RA. Overexpressed miR-411 or silencing RIPK1 inhibited the proliferation and promoted apoptosis of synoviocytes of RA mice. Up-regulation of miR-411 or down-regulation of RIPK1 had a certain inhibitory effect on RA. This study suggests that up-regulated miR-411 or down-regulated RIPK1 promoted apoptosis and inhibited proliferation of synoviocytes of RA mice, which may be related to the inhibition of NF-κB activation.
32051018 Tumour necrosis factor alpha promotes secretion of 14-3-3η by inducing necroptosis in mac 2020 Feb 12 BACKGROUND: 14-3-3η is an intracellular protein also detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA). It is closely related to disease activity and anti-cyclic citrullinated peptide antibody levels. However, the main source of 14-3-3η and the mechanism of its release into the extracellular space remain unclear. Addressing these two points was the main goal of the current study. METHODS: The source of 14-3-3η was investigated by immunostaining RA synovial tissue. Fibroblast-like synoviocytes, CD4(+) cells, and macrophages were selected as candidates among the various cell types in the synovial tissue. Phosphorylation of mixed-lineage kinase domain-like pseudokinase (MLKL) and cell death of macrophages were studied by phalloidin staining and electron microscopy after stimulation with an oxidative stress inducer (diamide) or tumour necrosis factor (TNF)-α. Extracellular 14-3-3η protein levels were examined by western blotting. RESULTS: Macrophages from the synovial tissue from RA, but not osteoarthritis, showed dense and widespread cytoplasmic staining for the 14-3-3η protein, co-localized with peptidylarginine deiminase 4. Swelling and membrane rupture of macrophages were induced by treatment with TNF-α, but not interleukin (IL) 6/soluble IL-6 receptor (sIL-6R). Increased MLKL phosphorylation followed by necroptosis was also induced in TNF-α-stimulated macrophages. Necrostatin-1, a necroptosis inhibitor, antagonized MLKL phosphorylation. High levels of 14-3-3η were detected in the culture supernatants of macrophages stimulated with diamide and TNF-α, but not IL-6/sIL-6R. CONCLUSIONS: Macrophages that highly express 14-3-3η undergo TNF-α-induced necroptosis with damage to the cellular structure, resulting in the secretion of 14-3-3η into the extracellular space. The current study provides a novel mechanism for 14-3-3η level increase in the RA synovial fluid.
31272806 Risk of medical complications following total hip or knee arthroplasty in patients with rh 2020 Feb OBJECTIVE: To investigate the risk of medical complications following total hip and knee arthroplasty (THA/TKA) among rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients; and, to assess the risk of complications among biologics-treated RA patients. METHODS: In a nationwide register-based study, patients with RA and OA with THA/TKA surgery between 2000 and 2015 were identified and followed up to 90 days after surgery for venous thromboembolism (VTE), myocardial infarction and stroke, and non-surgical infections, respectively. Information on treatment with biologics was obtained in the DANBIO rheumatology register to compare risks of complications with non-biologics treated. RESULTS: A total of 2899 and 112,571 patients with RA and OA had THA/TKA. RA was associated with a hazard ratio (HR) of 1.29 (1.03 to 1.61) for infection following THA/TKA, but a HR of 0.60 (0.26 to 0.98) for VTE following TKA. Biologics treated patients had a HR of 1.35 (0.65 to 2.80) for infection and 4.82 (1.67 to 13.90) for VTE compared with non-biologics treated RA patients. RA patients had no increased risk of post-surgical myocardial infarction and stroke (HR 1.16, 0.76 to 1.78) compared with OA, but a higher incidence proportion was observed in biologics treated compared with non-biologics treated (1.0% vs 0.6%); however, the number of events were too small to estimate a HR. CONCLUSION: In this study, RA was a risk factor for infection after THA/TKA, and RA patients treated with biologics had a slightly increased risk compared with non-biologics treated RA patients. Compared with OA, RA patients had a lower risk of VTE following THA/TKA, but our finding of increased incidences of VTE in biologics-treated patients warrants further studies.
32772699 Strongyloides stercoralis colitis in a patient positive for human T-cell leukaemia virus w 2021 Jan An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.
31682074 CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With 2020 Apr OBJECTIVE: Memory stem T (Tscm) cells are long-lived, self-renewing T cells that play a relevant role in immunologic memory. This study was undertaken to investigate whether Tscm cells accumulate in rheumatoid arthritis (RA). METHODS: The polarization and differentiation profiles of circulating T cells were assessed by flow cytometry. Antigen-specific T cells were characterized by staining with major histocompatibility complex class II tetramers. The T cell receptor (TCR) repertoire was analyzed by high-throughput sequencing using an unbiased RNA-based approach in CD4+ T cell subpopulations sorted by fluorescence-activated cell sorting. RESULTS: We analyzed the dynamics of circulating Tscm cells (identified as CD45RA+CD62L+CD95+ T cells) by flow cytometry in 27 RA patients, 16 of whom were also studied during treatment with the anti-tumor necrosis factor (anti-TNF) agent etanercept. Age-matched healthy donors were used as controls. CD4+ Tscm cells were selectively and significantly expanded in RA patients in terms of frequency and absolute numbers, and significantly contracted upon anti-TNF treatment. Expanded CD4+ Tscm cells displayed a prevalent Th17 phenotype and a skewed TCR repertoire in RA patients, with the 10 most abundant clones representing up to 53.7% of the detected sequences. CD4+ lymphocytes specific for a citrullinated vimentin (Cit-vimentin) epitope were expanded in RA patients with active disease. Tscm cells accounted for a large fraction of Cit-vimentin-specific CD4+ cells. CONCLUSION: Our results indicate that Tscm cells, including expanded clones specific for relevant autoantigens, accumulate in RA patients not exposed to biologic agents, and might be involved in the natural history of the disease. Further analysis of Tscm cell dynamics in autoimmune disorders may have implications for the design and efficacy assessment of innovative therapies.
31812101 Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflam 2020 Jan PURPOSE: Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery. METHODS: Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines. RESULTS: Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis. CONCLUSION: In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.
32610164 An imbalance between blood CD4(+)CXCR5(+)Foxp3(+) Tfr cells and CD4(+)CXCR5(+)Tfh cells ma 2020 Sep BACKGROUND: Follicular helper T (Tfh) cells are a subgroup of activated CD4(+) T cells which can assist the formation and maintenance of germinal centers. Follicular regulatory T (Tfr) cells are a new class of regulatory T cells which play a major role in suppressing cells in humoral immunity. In contrast to the role of Tfh cells, Tfr cells can inhibit the function of Tfh cells and B cells. Imbalance of blood Tfr/Tfh ratio resulted in the expansion of auto-reactive B cells and auto-antibody production (). However, the effect of Tfr cells and Tfh cells in the pathogenesis of RA (rheumatoid arthritis) is unclear. The purpose of this study was to investigate the function of Tfr cells and Tfh cells in the pathogenesis of RA. METHODS: We recruited 20 patients fulfilled the the American College of Rheumatology diagnosis criteria and 20 healthy controls (HCs). The number of CD4(+)CXCR5(+)Foxp3(+) Tfr cells and CD4(+)CXCR5(+) Tfh cells in 20 RA patients were measured by flow cytometry analysis. Furthermore, the correlations between the Tfr/Tfh ratio and the characteristic clinical parameters were assessed. The serum levels of IL-21(interleukin-21), CXCL13 (chemokine (C-X-C motif) ligand 13) and TGF-β (Transforming growth factor-β) were measured by ELISA. The formation of ectopic germinal center (GC) of synovial membrane was examined by H&E staining. The transcriptional levels of CXCR5 (C-X-C chemokine receptor type 5), CXCL13, ICOS (inducible co-stimulater) and TGF-β mRNA were also analyzed. In addition, the expression of Bcl-6 (B-cell lymphoma 6), CXCR5, CXCL13 and ICOS in synovial membrane were examined by immunohistochemistry. RESULTS: RA patients had more Tfh cells in peripheral blood, conversely, the frequency of blood Tfr cells (p < 0.05) and the ratio of Tfr/Tfh were significantly decreased compared to healthy controls (p < 0.05, p < 0.01). Furthermore, the ratio of Tfr/Tfh was negatively correlated with values of ESR (r=-0.57, p < 0.05), RF (r=-0.5275, p < 0.001), CRP (r=-0.4486, p < 0.001), IgG (r=-0.4631, p < 0.05), DAS28 scores (r=-0.5645, p < 0.01), as well as the levels of IL-21(r=-0.7398, p < 0.01), CXCL13 (r=-0.4832, p < 0.05). However, the ratio of Tfr/Tfh was positively with the serum level of TGF-β (r=0.5115, p < 0.05). Higher mRNA expression of CXCR5, CXCL13, ICOS and lower TGF-β mRNA expression were observed in RA patients. The serum expression level of IL-21, CXCL13 was significantly increased and expression of TGF-β was significantly decreased in RA patients. Furthermore, ectopic germinal center formation and higher expression of Bcl-6, CXCR5, ICOS, CXCL13 in the synovial membrane of the joints in RA patients were observed. CONCLUSIONS: The decreased blood CD4(+)CXCR5(+)Foxp3(+) Tfr cells/CD4(+)CXCR5(+) Tfh cells may be responsible for the immunopathogenesis of RA.
32096106 Protecting the Normal Physiological Functions of Articular and Periarticular Structures by 2020 Feb 24 Taking the articular and periarticular structures as a litmus test for gold-based nanoformulations, the potential of gold nanoparticles in protecting the normal physiological functions of these structures particularly in geriatric patients is one of the research areas of current interest. Aside from its use to make the traditional and fashionable ornaments for human usage, the gold metal is also known for its rich therapeutic activity. This is especially true when the gold is converted from its bulk form into nanosized form before its administering into the human body. Since it is the age of nanocomponents in medical and pharmaceutical research areas, this review is therefore mainly focused on nanoparticulate systems consisting of aurum. Accumulating research reports nevertheless show concrete evidence indicating the potential of gold-based nanoformulations to manage joint syndromes such as osteoarthritis and rheumatoid arthritis. This review embarks from preparation techniques and characterization methods to therapeutical application potentials of gold-based nanoformulations.
33242532 RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-T 2021 Feb 10 Excessive tumor necrosis factor-α (TNF-α) is associated with the pathogenesis of rheumatoid arthritis (RA). Approximately 90% of patients with RA, who have inadequate response to methotrexate, follow anti-TNF-α therapy as the first-line immuno-treatment. However, ineffective long-term anti-TNF-α antibody cycling for 40% of non-responders to anti-TNF-α antibodies is costly and associated with various side effects, which needs alternative mechanism of action therapies. In the present study, a novel strategy to down-regulate TNF-α level was developed by using an alternative method of suppressing TNF-α converting enzyme (TACE), a transmembrane enzyme involved in cleaving and releasing bioactive soluble TNF-α. TACE suppression can be an effective remedy to block the production of soluble TNF-α, leading to an increased sensitivity to anti-TNF-α non-responders. A disease site-targeted RNA interference system was developed by forming non-viral complex between shRNA against TACE (shTACE) and bone resorption site-specific peptide carrier composed of aspartate repeating and arginine repeating sequences. The shTACE/peptide carrier complex alleviated arthritic symptoms in collagen induced arthritis (CIA) models by demonstrating enhanced anti-inflammatory and anti-osteoclastogenic effects. Similar results were obtained with human primary synovial cells and osteoclast precursor isolated from tissues and synovial fluids of RA patients. Taken together, the shTACE/targeting peptide complex provides a strong potential as an alternative anti-TNF-α therapeutic for RA treatment.
32781326 Palmitic acid-modified bovine serum albumin nanoparticles target scavenger receptor-A on a 2020 Nov Palmitic acid-modified bovine serum albumin (PAB) was synthetized and found to own remarkable scavenger receptor-A (SR-A) targeting ability in vitro and in vivo, through which activated macrophages took up PAB nanoparticles (PAB NPs) 9.10 times more than bovine serum albumin nanoparticles (BSA NPs) and PAB NPs could delivery anti-inflammatory drugs celastrol (CLT) to inflamed tissues more effectively than BSA NPs. Compared with chondroitin sulfate modified BSA NPs targeting activated macrophages via CD44, PAB NPs show a more prominent targeting effect whether in vivo or in vitro. And PAB also demonstrated excellent biosafety compared to maleylated BSA, a known SR-A ligand that was lethal in our study. Furthermore, in adjuvant-induced arthritis rats, CLT-PAB NPs significantly improved disease pathology at a lower CLT dose with high safety, compared with CLT-BSA NPs. In addition, compared with the existing ligands with SR-A targeting due to strong electronegativity, the enhanced electronegativity and introduced PA are both important for the SR-A targeting effect of PAB. Therefore, PAB provides a novel direction for the treatment of rheumatoid arthritis and design of new ligands of SR-A.
30710453 I Would Never Take Preventive Medication! Perspectives and Information Needs of People Who 2020 Mar OBJECTIVE: Little is known about the experiences, values, and needs of people without arthritis who undergo predictive biomarker testing for the development of rheumatoid arthritis (RA). Our study aimed to explore the perspectives of these individuals and describe their information needs. METHODS: A qualitative, multicenter interview study with a thematic analysis was conducted in Austria, Germany and the UK. Individuals were interviewed who underwent predictive biomarker testing for RA and had a positive test result but no diagnosis of any inflammatory joint disease. Participants included patients with arthralgia and asymptomatic individuals. Information and education needs were developed from the qualitative codes and themes using the Arthritis Educational Needs Assessment Tool as a frame of reference. RESULTS: Thematic saturation was reached in 34 individuals (76% female, 24 [71%] with arthralgia, and 10 [29%] asymptomatic individuals). Thirty-seven codes were summarized into 4 themes: 1) decision-making around whether to undergo initial predictive testing, 2) willingness to consider further predictive tests, and/or 3) preventive interventions, including medication, and 4) varying reactions after receiving a positive test result. Individuals with arthralgia were more likely to be willing to take preventive action, undergo further testing, and experience psychological distress than asymptomatic individuals. All participants expressed the need for tailored, patient-understandable information. CONCLUSION: Individuals at risk of RA are currently the subjects of research aimed at developing better predictive strategies and preventive approaches. Their perceptions and needs should be addressed to inform the future development of interventions combined with education.
33219453 COVID-19 in rheumatoid arthritis cases: an Iranian referral center experience. 2021 Jul Coronavirus infections, known as COVID-19, can induce a fatal respiratory system infection and also affect other organs, such as the kidney and heart. The mortality rate has been estimated between 1 and 5% in previous reports; however, the mortality and morbidity can be higher in patients with the immune-deficiency condition. Rheumatoid arthritis (RA) is one of the most rheumatoid disorders, and it is important to report their clinical and paraclinical data when affected with COVID-19. Evidence about their laboratory and radiologic findings is limited. In this case series, 10 cases of chronic and approved rheumatoid arthritis (RA) affected by COVID-19 are presented. Only 40% had dry cough, but myalgia and weakness as the general first presentation of infections was reported in most cases (80%). Gastrointestinal symptoms, including nausea/vomiting, diarrhea, anorexia, and abdominal pain, were reported in 50% of individuals. In blood cell count, 30% of cases had thrombocytopenia, and ESR in all cases was positive. Abnormal CRP and elevated LDH were seen in 90% of cases. In HRCT assessment, all cases had an abnormal parenchymal pattern, and 90% of cases presented the usual pattern of COVID-19 (bilateral multifocal GGO/consolidation). Although it is a limited report, these findings are helpful for comparison of clinical and paraclinical cases in RA cases with normal cases.
33075379 Dexamethasone Sodium Phosphate Loaded Modified Cyclodextrin Based Nanoparticles: An Effici 2021 Mar The main aim of the current research was to develop a modified cyclodextrin based nanoparticulate drug delivery system to deliver dexamethasone sodium phosphate (DSP) for the treatment of rheumatoid arthritis (RA). DSP is a glucocorticoid (GC), and its limited application in RA therapy due to poor pharmacokinetics and its severe associated side effects. DSP loaded hydrophobically modified cyclodextrin based nanoparticles (DSP-NPs) prepared by a double emulsion solvent evaporation method. The nanoparticle size was <120 nm, good entrapment efficiency and excellent stability were obtained. TEM study showed that nanoparticles were perfectly spherical shape. The in-vitro drug release from nanoparticle follows the non-Fickian diffusion mechanism. The pharmacokinetic profile of DSP after encapsulation showing the 2.3-fold increase in AUC and extended mean residence time, which increases the chances of nanoparticles to extravasate into the site of inflammation by the EPR effect. The pharmacodynamic studies in the Adjuvant-induced Arthritis (AIA) rat model showing a significant reduction in arthritic score, paw thickness, and inflammatory cytokine level in serum. Adverse effects evaluation studies demonstrate a significant reduction in the associated undesirable effects on body weight, blood glucose level, renal impairment, and hematological abnormalities compared to marketed formulation. These results suggest that DSP-NPs can be used as an efficient therapy for RA.
33095141 What about glucocorticoids in primary Sjögren's syndrome? 2020 Jul Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions, reproduction. Furthermore, they exert different effects on innate and adaptive immune cells. Due to their anti-inflammatory and immunosuppressive functions, these drugs are largely used for the treatment of inflammatory and autoimmune diseases. In comparison to other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to date no reliable evidence is available for the use of systemic GCs in Sjögren's syndrome (SS), which is still based on case reports, case studies, retrospective or prospective studies and a small number of randomised controlled trials (RCTs). Despite this gap in our knowledge, GCs are commonly used in SS for glandular, joint, cutaneous, lung, haematological, renal, neurological involvement. More recently, some sets of recommendations for the management of SS have provided a few pieces of advice regarding the use of GCs in this condition. Future studies should not neglect the role of GCs, as this traditional therapeutic weapon can still have a role in the management of SS. Accordingly, this review will address and discuss the use of systemic GCs in isolated or primary SS.
32377959 Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2020 Dec Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p < 0.001). The decrease affected women (22% to 17%) and men (14% to 8%) in all age groups and both short-term (≤ 2-year disease duration: 9% to 3%) and long-term RA patients (> 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.
31859424 Singapore Chapter of Rheumatologists updated consensus statement on the eligibility for go 2020 Feb INTRODUCTION: Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). However, widespread use of biologic DMARDs (bDMARDs) and targeted-synthetic (tsDMARDs) is limited by cost. We formulated updated recommendations for eligibility criteria for government-assisted funding of bDMARDs/tsDMARDs for RA patients in Singapore. MATERIALS AND METHODS: Published guidelines regarding use of bDMARD and tsDMARDs were reviewed. We excluded those without a systematic literature review, formal consensus process or evidence grading. Separately, unpublished national reimbursement guidelines were included. RESULTS: Eleven recommendations regarding choice of disease activity measure, initiation, order of selection and continuation of bDMARD/tsDMARDs were formulated. A bDMARD/tsDMARD is indicated if a patient has: (a) at least moderately active RA with a Disease Activity Score in 28 joints/erythrocyte sedimentation rate (DAS28-ESR) score of ≥3.2; (b) failed ≥2 csDMARD strategies, 1 of which must be a combination; (c) received an adequate dose regimen of ≥3 months for each strategy. For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered. If a first-line TNFi fails, options include another TNFi, non-TNFi biologic or tsDMARDs. If a first-line non-TNFi biologic or tsDMARD fails, options include TNFi or another non-TNF biologic or tsDMARD. For continued bDMARD/tsDMARD subsidization, a patient must have a documented DAS28-ESR every 3 months and at least a moderate European League Against Rheumatism response by 6 months. CONCLUSION: These recommendations are useful for guiding funding decisions, making bDMARD/tsDMARDs usage accessible and equitable in RA patients who fail csDMARDs.
33315331 Rheumatoid arthritis medication adherence in a health system specialty pharmacy. 2020 Dec 1 OBJECTIVES: To assess adherence to specialty medications for rheumatoid arthritis (RA) at an integrated health system specialty pharmacy (HSSP) and identify characteristics associated with adherence. STUDY DESIGN: Single-center, retrospective cohort study. METHODS: Study patients were adults with RA who filled at least 3 prescriptions for biologic disease-modifying antirheumatic drugs (bDMARDs) between July 1, 2016, and June 30, 2017, at an integrated HSSP. Data were collected from pharmacy claims and electronic health records. The primary outcome, adherence, was measured using proportion of days covered (PDC). Proportional odds logistic regression was used to test association between PDC and age, gender, race, insurance type, and out-of-pocket costs. RESULTS: We included 675 patients: 77% were female, 90% were White, 29% were naive to treatment at initial dispensing, 60% held commercial insurance, and the median age was 56 years. Median (interquartile range [IQR]) patient out-of-pocket cost per fill was $1.50 ($0-$5). Median (IQR) PDC was 0.95 (0.84-1.00); 80% of patients achieved PDC of 0.80 or higher. Higher adherence was more likely in patients who were male (odds ratio [OR], 1.58; 95% CI, 1.15-2.18; P = .005], naive to specialty medication treatment (OR, 3.04; 95% CI, 2.21-4.18; P < .001), and older in age (per 10 years: OR, 1.17; 95% CI, 1.04-1.32; P = .008), and adherence had a significant nonlinear association with average cost per fill (P = .006); associations with race and insurance type were not significant. CONCLUSIONS: At an integrated HSSP, patients with RA paid low out-of-pocket costs for bDMARD therapy and achieved high treatment adherence. Data suggest that integrated HSSPs assist patients in removing financial barriers to treatment.