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ID PMID Title PublicationDate abstract
32357246 Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease 2020 Nov 1 OBJECTIVES: SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) - signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. METHODS: Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren's (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. RESULTS: SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. CONCLUSION: Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.
33216465 Animal models of rheumatoid arthritis-associated interstitial lung disease. 2021 Mar BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. AIMS: To provide guidance for those who are investigating the pathogenesis of RA-ILD with animal models. MATERIALS AND METHODS: An analysis of papers from PubMed during 1978-2020. RESULTS: We outline the present status quo for animal models of RA-ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. DISCUSSION: There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA-ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA-ILD. CONCLUSION: These established animal models of the disease can significantly progress our understanding of the etiology of RA-ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio-markers, and can contribute to the development and implementation of novel treatment strategies.
32993980 Therapeutic effects of celecoxib polymeric systems in rat models of inflammation and adjuv 2020 Sep The incidence of rheumatoid arthritis (RA), an autoimmune inflammatory disease, is rapidly increasing in aging societies. In the current study, celecoxib (CXB) micelles were developed to improve the oral absorption and anti-inflammatory effects of CXB in cell studies and λ-carrageenan rat models, and to enhance the therapeutic effects of CXB on RA in complete Freund's adjuvant (CFA)-induced RA rat models. Moreover, CXB micelles and previously developed solid dispersion (SD6) formulations were evaluated. The physical properties of optimal CXB micelles (M3), such as crystallinity, thermal properties, and intramolecular interactions, were altered. Compared with the commercial product (Celebrex®), the M3 and SD6 formulations showed significantly improved anti-inflammatory effects in terms of nitric oxide reduction, 1.5-fold and 2.2-fold, respectively, at the cellular level. The relative bioavailability (BA) of the M3 and SD6 formulations was also significantly improved as oral bioavailability (167.2% and 219.8% respectively), compared with that of Celebrex®. In particular, M3 and SD6 significantly reduced inflammation and edema volume relative to Celebrex® in CFA-induced RA rat models. Moreover, both M3 and SD6 effectively suppressed CFA-induced pro-inflammatory cytokines (TNF-α and IL-1β) in rat splenic tissues. In conclusion, polymeric systems improved the solubility, relative BA (%) and anti-inflammatory effects of CXB. Thus, CXB polymeric systems show potential as therapeutic agents against inflammation and RA and may need to be tested at the clinical level.
32384515 Does concomitant methotrexate confer clinical benefits in patients treated with prior biol 2020 May Most studies of methotrexate (MTX) in combination with tumor necrosis factor (TNF) inhibitors have focused on treatment-naive patients with early disease. The goal of this study was to evaluate whether previous biologic therapy influenced the impact of concomitant MTX in patients initiating treatment with adalimumab.We retrospectively analyzed data from 2 large noninterventional studies of German patients with active rheumatoid arthritis (RA) who initiated adalimumab therapy during routine clinical practice. Patients were seen between April 2004 and February 2013 for study 1 and between April 2003 and March 2013 for study 2. Key outcomes were Disease Activity Score-28 joints (DAS28), patient global assessment of health (PGA), and pain. Subgroup analyses by prior biologic treatment were performed on patients treated with continuous adalimumab monotherapy or adalimumab plus MTX for 12 months and 2-sample t tests were used to evaluate differences. We also assessed outcomes in subgroups in which MTX had been added or removed at 6 months and compared outcomes with 1-sample t tests.Of 2654 patients, 1911 (72%) were biologic naive and 743 (28%) had received prior biologic therapy, usually with a TNF inhibitor. All subgroups showed improvements following initiation of adalimumab therapy. In patients with no previous biologic treatment, continuous adalimumab plus MTX was associated with greater improvements in DAS28, PGA, and pain at month 12 compared with continuous adalimumab monotherapy (P = .0006, .0031, and .0032, respectively). In patients with previous biologic treatment, concomitant MTX was associated with statistically significant benefits in pain only. Adding MTX at month 6 resulted in additional benefits in patients with no prior biologic therapy, but not those with previous biologics.We conclude that concomitant MTX resulted in additional improvements in DAS28 and PGA vs adalimumab monotherapy in patients with no previous biologic therapy, but changes were not statistically significant in patients treated with prior biologics. These findings may help inform the patient/provider treatment decision during routine clinical care.
32441061 Risk prediction model in rheumatoid arthritis-associated interstitial lung disease. 2020 Dec BACKGROUND AND OBJECTIVE: RA-ILD has a variable clinical course, and its prognosis is difficult to predict. Moreover, risk prediction models for prognosis remain undefined. METHODS: The prediction model was developed using retrospective data from 153 patients with RA-ILD and validated in an independent RA-ILD cohort (n = 149). Candidate variables for the prediction models were screened using a multivariate Cox proportional hazard model. C-statistics were calculated to assess and compare the predictive ability of each model. RESULTS: In the derivation cohort, the median follow-up period was 54 months, and 38.6% of the subjects exhibited a UIP pattern on HRCT imaging. In multivariate Cox analysis, old age (≥60 years, HR: 2.063), high fibrosis score (≥20% of the total lung extent, HR: 4.585), a UIP pattern (HR: 1.899) and emphysema (HR: 2.596) on HRCT were significantly poor prognostic factors and included in the final model. The prediction model demonstrated good performance in the prediction of 5-year mortality (C-index: 0.780, P < 0.001); furthermore, patients at risk were divided into three groups with 1-year mortality rates of 0%, 5.1% and 24.1%, respectively. Predicted and observed mortalities at 1, 2 and 3 years were similar in the derivation cohort, and the prediction model was also effective in predicting prognosis of the validation cohort (C-index: 0.638, P < 0.001). CONCLUSION: Our results suggest that a risk prediction model based on HRCT variables could be useful for patients with RA-ILD.
32690598 Elevated levels of anti-carbamylated protein antibody in patients with rheumatoid arthriti 2020 Aug To measure the serum levels of anticarbamylated protein (CarP) antibodies in patients with rheumatoid arthritis (RA) in China and to evaluate the association of anti-CarP antibodies with clinical parameters and disease activity. 260 Chinese patients with RA, 40 patients with osteoarthritis (OA), 88 patients with spondyloarthritis (SpA) and 77 healthy controls were included. The serum levels of anti-CarP antibodies were detected by ELISA. Blood tests to detect the anticyclic citrullinated peptide (CCP) antibody level, rheumatoid factor (RF) level, erythrocyte sedimentation rate, C reactive protein level and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) were performed by standard methods. Bone erosion was assessed by colour Doppler ultrasonography. A total of 18.8% of patients with RA and 9.4% of anti-CCP antibody and RF-double-negative patients were positive for anti-CarP antibody. The anti-CarP antibody level was significantly higher in patients with RA than in patients with OA or SpA and in healthy controls. Univariate and multivariate analyses showed that the level of anti-CarP antibody was positively correlated with DAS28-ESR; the higher a level of serum anti-CarP antibody, the higher the DAS28-ESR score. Anti-CarP-positive patients had higher disease activity scores than anti-CarP-negative patients. Moreover, anti-CarP-positive patients had a higher risk of developing bone erosion. The anti-CarP antibody was found to play an important role in the diagnosis of RA, especially in anti-CCP antibody and RF-double-negative patients. The anti-CarP antibody is a potential marker of disease activity and bone erosion in RA.
32061742 Andrographolide ameliorates oxidative stress, inflammation and histological outcome in com 2020 Mar 1 OBJECTIVES: As one of the main active ingredients of Chinese herbal medicine Andrographis paniculate, andrographolide is used in domestic clinical treatment for respiratory infections and inflammation. This study was designed to investigate the effects of andrographolide as an antioxidant on the level of oxidative stress, neutrophil accumulation and infiltration in joints and synovial tissue of arthritis rats induced by complete freund's adjuvant. METHODS: A rat model of rheumatoid arthritis was induced by subcutaneous injection of complete Freund's adjuvant in the footpad. The model was established 14 days after induction. The treatment was performed from 14th day to 35th day with different doses of andrographolide (25, 50, 100 mg/kg) and positive control methotrexate (3 mg/kg). The effects of andrographolide on oxidative stress, neutrophil accumulation and infiltration were measured by the paw swelling, arthritis score, the hot plate test, biochemical analysis, and histology. RESULTS: The medium and high-dose andrographolide (50, 100 mg/kg) group declined the levels of tumor necrosis factor-α, interleukin-6 and CXC chemokine ligand2, articular elastase and myeloperoxidase, and increased the levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione. The activity of malondialdehyde and nitrite/nitrate in andrographolide (50, 100 mg/kg) group was weakened than the model group. The degree of swelling and arthritis score of andrographolide group was lower than the model group. The results of hot plate test showed that high dose of andrographolide significantly improved the anti-injury ability of rats; Radiological and histological results showed that the joint osteoporosis, inflammatory cell infiltration, synovial hyperplasia and other phenomena in the andrographolide group were significantly improved. CONCLUSIONS: Andrographolide acts as a protective agent for the treatment of complete freund's adjuvant induced rheumatoid arthritis by inhibiting lipid peroxidation and nitrite/nitrate levels in a dose-dependent manner, enhancing antioxidant enzyme activity, reducing levels of chemokines and inflammatory factors, preventing neutrophil accumulation and infiltration.
32311948 Favorable retention rates and safety of conventional anti-rheumatic drugs in older patient 2020 Apr Physicians are challenged by the recognition and treatment of older patients with rheumatoid arthritis (RA). The aim of this case-control study was to evaluate the retention and safety of conventional disease-modifying anti-rheumatic drugs in older patients with RA.In this observational case-control study, we assessed older patients with RA (≥65 years) who were diagnosed in 3 different rheumatology centers from Turkey. Patients were divided as to those aged ≥65 years (elderly rheumatoid arthritis [ERA]) and those aged <65 years (young rheumatoid arthritis [YRA]) at the time of conventional DMARD treatment initiation. The Mann-Whitney U test was used for the comparison of 2 non-normally distributed groups. The Chi-square (χ) test was used for categorical variables. Survival analysis were performed using the Kaplan-Meier method.Four hundred eighteen patients with RA (296 females [71%]) were included from January 2010 to January 2018. The age of treatment onset of 190 (47%) patients was in the elderly period and they were included in the ERA group. In the analysis of drug retention rates, there was no significant difference between the ERA and YRA groups for each conventional DMARD (methotrexate 71.2% in ERA, 62.7% in YRA, P = .817; hydroxychloroquine 82.9% in ERA, 78.8% in YRA, P = .899; leflunomide 81.4% in ERA, 84.4% in YRA, P = .205; sulfasalazine 37.5% in ERA, 40.9% in YRA, P = .380). The adverse event data were also similar in both groups.The drug retention and adverse effect rates in older patients with RA using conventional DMARDS are similar to the rates in young patients with RA.
32076792 Acetabular cup migration after primary cementless total hip arthroplasty in rheumatoid art 2020 Jun PURPOSE: To compare the radiographic migration profiles of primary cementless total hip arthroplasty (THA) between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). METHODS: A total of 197 patients (215 hips) who underwent cementless THA for RA or OA between January 2001 and January 2013 and followed up for a minimum of 5.5 years were included. Ninety-four RA patients (109 hips) were compared with 103 OA patients (106 hips). Radiological evaluation was performed for acetabular cup loosening, and cup migration was measured using Einzel-Bild-Röntgen-Analyse (EBRA) software. Multiple variables were assessed to identify influencing factors for cup migration. RESULTS: Early cup migration was observed in 13 hips (11.9%) in the RA group and four hips (3.8%) in the OA group, showing a significant difference (p = 0.041). Acetabular cup loosening occurred in three cups (2.8%) in the RA group and in one cup (0.9%) in the OA group, showing no significant difference (p = 0.321). Total cup migration was higher in the RA group (2.62 mm) than in the OA group (1.44 mm, p = 0.005). Total cup migration was significantly higher in patients aged < 50 years than in those aged > 50 years (p = 0.005). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody influenced total cup migration. Patients with seropositive RA showed significantly higher total cup migration and early cup migration incidence than those with seronegative RA (p = 0.005, p = 0.038, respectively). CONCLUSIONS: Acetabular cups in primary cementless THAs of RA patients were less stable in terms of cup migration compared with that of OA patients.
33298503 Non-infective supraglottitis: two cases of unusual aetiology. 2020 Dec 9 Supraglottitis is an ear, nose and throat emergency where swelling of the laryngeal structures can threaten to fatally obstruct the airway. Most cases of supraglottitis are of infective origin but other rarer causes have been documented. We present two patients who presented with stridor and were found to have supraglottic oedema on fibreoptic nasolaryngoscopy. Both patients presented with odynophagia and progressive dyspnoea and were initially medically managed to stabilise their airway. This included intravenous steroids, nebulised epinephrine and intravenous antibiotics. After this initial treatment they both required investigation and optimisation of their underlying medical conditions (rheumatoid arthritis with possible systemic lupus erythematosus and nephrotic syndrome) as more definitive management.
33258004 Different types of physical activity are positively associated with indicators of mental h 2021 Feb Nationwide lockdowns during SARS-CoV-2 (COVID-19) can compromise mental health and psychological wellbeing and limit opportunities for physical activity (PA), particularly in clinical populations, such as people with rheumatoid arthritis (RA), who are considered at risk for COVID-19 complications. This study aimed to investigate associations between PA and sedentary time (ST) with indicators of mental health and wellbeing in RA during COVID-19 lockdown, and examine the moderation effects of self-isolating. 345 RA patients completed an online questionnaire measuring PA (NIH-AARP Diet and Health Study Questionnaire), ST (International Physical Activity Questionnaire-Short Form), pain (McGill Pain Questionnaire and Visual Analogue Scale), fatigue (Multidimensional Fatigue Inventory), depressive and anxious symptoms (Hospital Anxiety and Depression Scale), and vitality (Subjective Vitality Scale) during the United Kingdom COVID-19 lockdown. Associations between PA and ST with mental health and wellbeing were examined using hierarchical multiple linear regressions. Light PA (LPA) was significantly negatively associated with mental fatigue (β = - .11), depressive symptoms (β = - .14), and positively with vitality (β = .13). Walking was negatively related to physical fatigue (β = - .11) and depressive symptoms (β = - .12) and positively with vitality (β = .15). Exercise was negatively associated with physical (β = - .19) and general (β = - .12) fatigue and depressive symptoms (β = - .09). ST was positively associated with physical fatigue (β = .19). Moderation analyses showed that LPA was related to lower mental fatigue and better vitality in people not self-isolating, and walking with lower physical fatigue in people self-isolating. These findings show the importance of encouraging PA for people with RA during a lockdown period for mental health and wellbeing.
32867752 Repository corticotropin injection attenuates collagen-induced arthritic joint structural 2020 Aug 31 BACKGROUND: Melanocortin receptor (MCR) agonists have anti-inflammatory and immunomodulatory properties mediated by receptors expressed on cells relevant to arthritis. Repository corticotropin injection (RCI; Acthar® Gel), an MCR agonist preparation, is approved as adjunctive therapy for rheumatoid arthritis (RA), but its mechanism of action in RA is unclear. This study explored the efficacy of RCI as monotherapy or adjunctive therapy with etanercept (ETN) in an established animal model of collagen-induced arthritis (CIA). METHODS: After induction of CIA, rats (n = 10 per group) were randomized to receive subcutaneous RCI (40, 160, or 400 U/kg twice daily) alone or in combination with ETN (10 mg/kg 3 times daily), ETN alone, or vehicle (on days 13 through 19). Inflammation was assessed via changes in paw edema. Bone damage was determined by microfocal computed tomography histopathology, and immunohistochemistry. Statistical analyses were performed using a 2-way analysis of variance (ANOVA) followed by the Newman-Keuls, Dunn's, or Dunnett's multiple comparisons test or a 1-way ANOVA followed by the Dunnett's or Holm-Sidak multiple comparisons test. RESULTS: RCI administration resulted in dose-dependent decreases in ankle edema and histopathologic measures of inflammation, pannus formation, cartilage damage, bone resorption, and periosteal bone formation. RCI and ETN showed combined benefits on all parameters measured. Radiographic evidence of bone damage was significantly reduced in rats that received RCI alone or in combination with ETN. This reduction in bone density loss correlated with decreases in the number of CD68-positive macrophages and cathepsin K-positive osteoclasts within the lesions. CONCLUSIONS: As monotherapy or adjunctive therapy with ETN, RCI attenuated CIA-induced joint structural damage in rats. These data support the clinical efficacy of RCI as adjunctive therapy for patients with RA.
33188511 M-134, a novel HDAC6-selective inhibitor, markedly improved arthritic severity in a rodent 2021 Feb BACKGROUND: Although tofacitinib has shown highly significant efficacy for rheumatoid arthritis (RA), there are still a considerable number of patients that are non-responders owing to its limited effectiveness and various adverse effects. Thus, alternative options with better efficacy and lower toxicity are desired. Here, M-134, a recently developed HDAC6 inhibitor, was examined for its therapeutic potential when combined with tofacitinib in a rat model of RA. METHODS: The single or combined administration of M-134 and tofacitinib was examined in complete Freund's adjuvant-induced arthritis (AIA) or collagen-induced arthritis (CIA) rodent models. To evaluate the therapeutic and adverse effects, the following factors were observed: macroscopic or microscopic scoring of all four paws; the expression of ICAM-1, VCAM-1, and IP-10 in the joints and that of various cytokines and chemokines in the plasma; the weight of the thymus and the liver; and changes in hematological enzymes. RESULTS: Combination treatment showed strong synergistic effects as measured by the clinical score and histological changes, without adverse effects such as weight loss in the thymus and increased liver enzymes (ALT and AST). Additionally, it also reduced ICAM-1, VCAM-1, and IP-10 expression in the joints, and M-134 increased the efficacy of tofacitinib by regulating various cytokines, such as interleukin (IL)-1β, IL-17, and TNF-α, in the serum of AIA rats. Differences in the cytokine expression for each drug were found in the CIA model. CONCLUSIONS: M-134 and tofacitinib combination therapy is a potential option for the treatment of RA through the regulation of cytokines, chemokines, and adhesion molecules.
31578612 [Treatment of psoriatic arthritis : Are there differential indications?]. 2020 Feb Psoriatic arthritis (PsA) is a very heterogeneous immune-mediated disease that usually involves skin and joints but can also affect entheses and extra-articular structures during the disease course. Furthermore, it can also be linked with other associated diseases. Therefore, the individualized selection of an effective and patient-oriented treatment must be carried out taking the extent of various manifestations of the PsA itself and also of other influencing factors into consideration. Various recommendations for selection and control of the suitable treatment of PsA are available for clinical use. The recommendations of the European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are the two recommendations that are frequently used and internationally acknowledged. Both recommendations were updated in 2016. Specific German treatment recommendations are currently missing. In analogy to the treat-to-target strategy for rheumatoid arthritis, at least minimal disease activity (MDA) should be achieved in PsA patients with the use of specific therapeutic interventions if remission as the maximum therapeutic goal cannot be reached. New treatment options, which target different specific molecules, offer possibilities for a more differentiated personalized medicinal treatment for improvement of the care of PsA patients. This particularly applies to a focus on personalized strategies for optimal treatment of various manifestation forms and patterns.
31154414 Magnetic Resonance Imaging (MRI) Results Following Discontinuation of Methotrexate in Rheu 2020 Mar OBJECTIVE: To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX. METHODS: In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to discontinue MTX (TCZ monotherapy; mono) or continue TCZ + MTX until Week 52. In a subset of patients, 1.5-Tesla MRI was used to obtain images of bilateral hands and wrists at weeks 24 and 40. Outcomes included changes in MRI-assessed synovitis, osteitis, erosion, and cartilage loss from Week 24 to Week 40, and in the proportion of patients with progression of each score. RESULTS: Of 296 patients who achieved DAS28-ESR ≤ 3.2 at Week 24, 79 were enrolled in the pilot MRI substudy and randomized to TCZ mono (n = 38) or TCZ + MTX (n = 41). Treatment with either TCZ mono or TCZ + MTX suppressed erosion progression, synovitis, osteitis, and cartilage loss. The proportion of patients with no progression in each outcome measure was similar between groups (range, TCZ mono: 84.8-97.0%; TCZ + MTX: 92.3-100%). CONCLUSION: In a subset of patients who achieved low disease activity with TCZ + MTX, MRI changes were minimal in intraarticular inflammation and damage measures in patients who discontinued MTX versus those who continued TCZ + MTX.
32423942 Foot health and quality of life in patients with rheumatoid arthritis: a cross-sectional s 2020 May 17 OBJECTIVE: The aim of this study is to identify foot health factors related to the quality of life in patients with rheumatoid arthritis (RA). SETTING: In this cross-sectional study, a total of 293 subjects were analysed, 229 of whom were in the RA group and 64 in the control group. In the RA group, 173 patients were female, and 50 in the control group. PARTICIPANTS: Patients with foot pain and RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 rheumatoid arthritis classification criteria) and with foot pain but no RA were recruited (Granada, Spain). INTERVENTION: Two researchers independently interviewed the patients to obtain data for the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical data were obtained using the Short Form 12-Item questionnaire (quality of life) (primary outcome), Visual Analogue Scale for pain (VAS pain), the Manchester Foot Pain Disability Index (MFPDI) and the Foot Function Index (FFI). Anthropometric measurements were obtained using a foot measurement platform, the Foot Posture Index and the Manchester Scale of Hallux Valgus (secondary outcomes). RESULTS: Of the 293 subjects, 76.1% were female. Significant differences were observed between the RA and the control group (p<0.001) with regard to VAS pain (general, foot and hand), MFPDI and FFI. In terms of anthropometric measurements, significant differences were only recorded for midfoot and forefoot width (p=0.03). For the physical health component, multivariable linear regression with the parameters age, gender, VAS pain (general) and the presence of RA presented an R(2) value of 48.8%, while for the mental health component the corresponding value was 5.6%. CONCLUSION: Morphological and structural characteristics of the foot are not necessarily associated with pain, disability and loss of function. The presence of RA, a higher score on VAS pain (general), female gender and older age are all associated with the physical component of the quality of life of patients with RA.
32698454 Efficacy of Dietary Supplements in Inflammatory Bowel Disease and Related Autoimmune Disea 2020 Jul 20 The microbiome is an important contributor to a variety of fundamental aspects of human health, including host metabolism, infection, and the immune response. Gut dysbiosis has been identified as a contributor to the errant immune response in a variety of immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriatic disease (psoriasis and psoriatic arthritis). Given this, probiotics and prebiotics have been investigated as therapeutic options in these disease states. In our review, we highlight the current evidence on prebiotics and probiotics as well as other supplements (such as fish oils, vitamin D, and curcumin) as therapies for IBD. Recommendations, however, regarding the specific use of such supplements in IBD have been lacking, particularly from professional societies, often due to study limitations related to small sample sizes and design heterogeneity. Hence, we additionally examine the literature on the use of prebiotics, probiotics, and other supplements in related IMIDs, namely RA and psoriasis/psoriatic arthritis, as these diseases share many approved therapeutic options with IBD. Based on these combined findings, we offer additional evidence that may help guide clinicians in their treatment of patients with IBD (and other IMIDs) and provide recommendations on potential next steps in therapeutic research in this area.
32696744 [Decreased long-chain non-coding RNA MALAT1 expression and increased hsa-miR155-3p express 2020 Jun Objective To observe the expression of long-chain non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and hsa-miR155-3p in patients with rheumatoid arthritis (RA) and their relationship with Notch signaling pathway, and to explore the possible pathogenesis of RA. Methods Peripheral blood of RA patients (RA group) and healthy controls (NC group) were used to screen differentially expressed lncRNA and mRNA by high-throughput gene sequencing. Reverse-transcription PCR was used to detect the expression of lncRNA MALAT1, hsa-miR155-3p and Notch signaling pathway receptor ligands. Results The lncRNA sequencing analysis showed a total of 9158 differentially expressed lncRNAs. Gene ontology (GO) functional classification annotations revealed that the differentially expressed mRNA was mainly involved in immune inflammatory response, cellular transcriptional regulation and so on. Pathway analysis proved that differentially expressed mRNA was significantly related to the genes involved in rheumatoid arthritis, cellular senescence, and Notch signaling pathways. According to cis and trans prediction, Jagged1-2, Delta1-2 and Notch1-2 might be closely related to RA. MALAT1 in the RA group was lower than that in the NC group, and hsa-miR155-3p expression was significantly higher than that in the NC group. The expression of Notch pathway ligands Delta1, Delta2 Jagged1, Jagged2 and the receptors Notch1 and Notch2 in the RA group increased. Correlation analysis showed that hsa-miR155-3p was inversely proportional to MALAT1, hsa-miR155-3p was directly proportional to Notch pathway Delta1, Jagged1, and MALAT1 was inversely proportional to Jagged2. Conclusion In patients with rheumatoid arthritis, lncRNA MALAT1 is reduced and hsa-mir155-3p is raised, which jointly regulate the change of Notch signaling pathway.
31631321 Bayesian design of biosimilars clinical programs involving multiple therapeutic indication 2020 Jun In this paper, we propose a Bayesian design framework for a biosimilars clinical program that entails conducting concurrent trials in multiple therapeutic indications to establish equivalent efficacy for a proposed biologic compared to a reference biologic in each indication to support approval of the proposed biologic as a biosimilar. Our method facilitates information borrowing across indications through the use of a multivariate normal correlated parameter prior (CPP), which is constructed from easily interpretable hyperparameters that represent direct statements about the equivalence hypotheses to be tested. The CPP accommodates different endpoints and data types across indications (eg, binary and continuous) and can, therefore, be used in a wide context of models without having to modify the data (eg, rescaling) to provide reasonable information-borrowing properties. We illustrate how one can evaluate the design using Bayesian versions of the type I error rate and power with the objective of determining the sample size required for each indication such that the design has high power to demonstrate equivalent efficacy in each indication, reasonably high power to demonstrate equivalent efficacy simultaneously in all indications (ie, globally), and reasonable type I error control from a Bayesian perspective. We illustrate the method with several examples, including designing biosimilars trials for follicular lymphoma and rheumatoid arthritis using binary and continuous endpoints, respectively.
32824469 Misperception of the Cardiovascular Risk in Patients with Rheumatoid Arthritis. 2020 Aug 17 The risk of cardiovascular (CV) disease and mortality is increased by rheumatoid arthritis (RA). However, data on how RA patients perceive their own CV risk and their adherence to CV prevention factors are scarce. We conducted an observational study on 266 patients with RA to determine whether the perceived CV risk correlates to the objective CV risk, and if it influences their compliance with a Mediterranean diet and physical exercise. The objective CV risk was calculated according to the modified European League Against Rheumatism (EULAR) Systematic Coronary Risk Evaluation (SCORE). The perceived CV risk did not correlate to the objective CV risk. The correlation was even lower when carotid ultrasound was used. Notably, 64.62% of patients miscalculated their CV risk, with 43.08% underestimating it. Classic CV risk factors, carotid ultrasound markers and ESR and CRP showed significant correlation with the objective CV risk. However, only hypertension and RA disease features showed association with the perceived CV risk. Neither the objective CV risk nor the perceived CV risk were associated with the accomplishment of a Mediterranean diet or physical activity. In conclusion, RA patients tend to underestimate their actual CV risk, giving more importance to RA features than to classic CV risk factors. They are not concerned enough about the beneficial effects of physical activity or diet.