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ID PMID Title PublicationDate abstract
33666154 Failure of first anti-TNF agent in Takayasu's arteritis: to switch or to swap? 2021 Mar OBJECTIVES: Biologic drugs (bDMARD), especially TNF-α-inhibitors (TNFi), are used in refractory Takayasu's arteritis (TAK) patients. Up to 23% of patients are switched to a different bDMARD because of inefficacy. No data are available on which strategy is more efficient after TNFi failure. The aim of our study is to evaluate whether a switch or swap strategy should be preferred in TAK patients failing TNFis. METHODS: TAK patients treated with a second bDMARD after the failure of the first TNFi were identified from 3 referral centres. Patients were classified as switch if treated with a different TNFi, and swap if treated with a non-TNFi bDMARD. Baseline features were evaluated. Efficacy and safety of the second bDMARD at 6 and 12 months were assessed and a comparison between switch and swap patients was made. RESULTS: Twenty-four TAK patients were identified. Eleven patients (46%) were switched and 13 patients (54%) were swapped (12 to tocilizumab, 1 to ustekinumab). Baseline features of patients in the 2 groups were comparable. At 12 months, the second bDMARD was suspended in 4 switch (36%) and in 5 swap (42%) patients. Second biologic drug survival and relapse-free survival were equivalent between the two groups at 6 and 12 months. A vascular worsening was observed in 4 switch (40%) and 2 swap (25%) patients. Severe infections, myocardial infarction, ischemic stroke or cancer were recorded in no patient. CONCLUSIONS: Our retrospective study suggests that in first-line TNFi failure TAK patients both switch and swap strategies can be considered suitable approaches.
34397495 Sulfasalazine-Induced Toxic Epidermal Necrolysis: A Challenging Case During the COVID-19 P 2021 Jul COVID-19 is a major health issue, and patients with underlying conditions are more susceptible to catastrophic outcomes. Toxic epidermal necrolysis (TEN) is a severe systemic disease caused by an immune system hypersensitive reaction. We present a case of TEN induced following sulfasalazine administration that later on complicated with COVID-19, deep vein thrombosis, pulmonary emboli, and eventually death.
34049860 Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severi 2021 Sep OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.
34218934 [Diagnostic issues of Whipple's disease during chronic inflammatory rheumatism: About thre 2021 Nov INTRODUCTION: Whipple's disease (WD) can mimic chronic inflammatory rheumatism leading to incorrect prescription of tumor necrosis factor inhibitors (TNFI). Several complicated cases of WD have been reported during TNFI treatment which is strongly suspected to modify the host-pathogen relationship. Tropheryma whipplei asymptomatic carriage is high in the general population, making the diagnosis of WD more difficult face to unexplained arthritis. OBSERVATIONS: We report three observations that illustrate situations for which the detection of T. whipplei might be valuable to investigate the differential diagnosis of inflammatory rheumatism. CONCLUSION: The decision to check for T. whipplei infection should rely on individual clinical assessment. It should be considered in the absence of clinical response or in case of worsening of an inflammatory rheumatism under TNFI treatment, especially in front of atypical features. A systematic screening for T. whipplei before anti-TNF treatment seems unjustified since asymptomatic carriers are frequent.
33982900 Relationship Between Rheumatoid Arthritis and Pulmonary Function Measures on Spirometry in 2021 Nov OBJECTIVE: To investigate the independent relationship of rheumatoid arthritis (RA) to the type and severity of pulmonary patterns on spirometry compared to the pulmonary patterns in general population controls. METHODS: In this cross-sectional study, we investigated the association of RA with pulmonary function measures on spirometry among subjects in the UK Biobank who underwent spirometry for research purposes. RA cases were identified based on self-report and current disease-modifying antirheumatic drug/glucocorticoid use. Controls were subjects without RA from the general population. Outcome measures included continuous forced expiratory volume in 1 second percent predicted (FEV(1) %) and forced vital capacity percent predicted (FVC%), type of spirometric pattern (restrictive or obstructive), and severity of the restrictive or obstructive pattern. We used multivariable regression to estimate the effects in RA cases compared to the effects in controls, adjusting for age, sex, body mass index, and smoking status/pack-years. RESULTS: Among 350,776 analyzed subjects who underwent spirometry (mean age 56.3 years; 55.8% female; 45.5% ever smokers), we identified 2,008 cases of treated RA. In multivariable analyses, RA was associated with lower FEV(1) % (β = -2.93 [95% confidence interval (95% CI) -3.63, -2.24]), FVC% (β = -2.08 [95% CI -2.72, -1.45]), and FEV(1) /FVC (β = -0.008 [95% CI -0.010, -0.005]) compared to controls. RA was additionally associated with restrictive patterns (odds ratio [OR] 1.36 [95% CI 1.21, 1.52]) and obstructive patterns (OR 1.21 [95% CI 1.07, 1.37]) independent of confounders, and was most strongly associated with severe restrictive and obstructive patterns. CONCLUSION: RA is associated with increased odds of restrictive and obstructive patterns, and this relationship is not explained by confounders, including smoking status. In addition to restrictive lung disease, clinicians should also be aware that airway obstruction may be a pulmonary manifestation of RA.
33831424 Therapeutic prospects of MicroRNAs carried by mesenchymal stem cells-derived extracellular 2021 Jul 15 Autoimmune diseases (ADs) are a class of chronic disease conditions with impaired tolerance to autoantigens. Currently, there is no effective treatment for ADs, and the existing medications have limitations due to non-specific targets and side effects. Accumulating evidence has shown that mesenchymal stem cells (MSCs) play a role in ADs treatment. These beneficial effects mainly rely on cell-to-cell communication through the secretion of extracellular vesicles (EVs) and soluble factors. MSC-derived EVs (MSC-EVs) could modulate adjacent and distinct cells by transferring various DNA, mRNA, non-coding RNAs, proteins, and lipids from parent cells to recipient cells. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate multiple target genes at the post-transcriptional level and are involved in chronic inflammatory and immune processes. Compared to fluid, MSC-EVs delivery can protect miRNAs from the degradation of ribonucleases, ensuring that miRNAs are able to perform their respective crucial roles in AD recipient cells. In this review, we discussed the therapeutic prospects and challenges of miRNAs secreted by MSC-EVs (MSC-EV-miRNAs) by reviewing the experimentally verified therapeutic outcomes of MSC-EV-miRNAs for several ADs, including rheumatoid arthritis (RA), autoimmune hepatitis (AIH), asthma, colitis, systemic sclerosis (SSc) and graft-versus-host disease (GVHD).
33792986 A novel CD209 polymorphism is associated with rheumatoid arthritis patients in Taiwan. 2021 May Single nucleotide polymorphisms (SNPs) in the promoter region of CD209 (cluster of differentiation 209) may influence expression levels, and higher expression of CD209 on immune cells correlate with severity of cartilage destruction in patients with rheumatoid arthritis (RA). Due to the lack of a comprehensive study, this study aimed to investigate the CD209 promoter variants and haplotypes in a Taiwanese population and the association with RA development. Deoxyribonucleic acid (DNA) of peripheral blood mononuclear cells from 126 RA patients and 124 healthy controls was purified, and the CD209 gene promoter was amplified by polymerase chain reaction and analyzed by Sanger sequencing. Results showed that a novel variant -96C>A polymorphism in CD209 promoter was identified in the Taiwanese population, and the frequency was significantly higher in RA patients than in controls (11.51% vs. 2.42%, P < .0001). The odds ratio (OR) for the development of RA was 5.88 (95% CI 2.35-14.74, P < .0001). Other known variants were also evaluated; for instance, -1180 T/T (rs7359874) was increased in RA patients, and the OR for the development of RA was 3.26, 95% CI 0.85-12.52, P = .07). Besides, the haplotype frequencies were calculated; -1180A-939C-871 T-336 T-139 T-96A and -1180 T-939 T-871C-336 T-139C-96A were increased in RA patients (P = .004 and 0.05, respectively). In summary, CD209-96A variant could be an important factor for the development of RA in the Taiwanese population.
32653654 Comparison of paediatric and adult classification criteria in juvenile idiopathic arthriti 2021 Jan OBJECTIVES: To determine the characteristics of juvenile idiopathic arthritis (JIA) patients seen during the transition period in order to compare paediatric classification criteria with those for adults. METHODS: Patients with JIA according to the ILAR classification and who had a consultation at transition between 2010 and 2017 were included in a retrospective bi-centre (Lyon, Lausanne) study. JIA classification criteria were compared to ACR/EULAR 2010 criteria for rheumatoid arthritis (RA), Yamaguchi criteria for adult-onset Still's disease (AOSD), ASAS criteria for spondyloarthritis and CASPAR criteria for psoriatic arthritis. RESULTS: One hundred and thirty patients were included: 13.9% with systemic JIA, 22.3% with polyarticular JIA, 22.3% with oligoarticular JIA, 34.6% with enthesitis-related arthritis (ERA) and 6.9% with psoriatic arthritis; 13.1% had suffered from uveitis; 14.5% of patients had erosions or carpitis, mainly those with psoriatic arthritis, polyarticular or systemic JIA; 37.5% of patients with ERA displayed radiological sacroiliitis. When comparing paediatric JIA criteria with adult classifications, we found that: 66.6% of patients with systemic JIA fulfilled the criteria for AOSD, 87.5% of rheumatoid factor-positive polyarticular JIA and 9.5% of rheumatoid factor-negative polyarticular JIA met the criteria for RA, and 34.5% of oligoarticular JIA fulfilled the criteria for spondyloarthritis. Finally, 77.7% of patients with ERA met the criteria for spondyloarthritis, and 100% of patients with psoriatic arthritis JIA met the criteria for psoriatic arthritis. CONCLUSION: Oligoarticular JIA and rheumatoid factor-negative polyarticular JIA seem to be paediatric entities, whereas the other types of JIA tended to meet the respective adult classification criteria.
34836794 Mangiferin exert protective effects on joints of adjuvant-induced arthritis rats by regula 2021 Dec BACKGROUND: Mangiferin (MF) is a bioactive ingredient predominantly isolated from the mango tree, that has been reported to have antioxidant, anti-inflammatory, and immunomodulatory effects. This study was aimed to investigate the protective effect of MF on the joints of arthritic rats and explore the underlying mechanisms of this function. METHODS: Adjuvant-induced arthritis (AA) rat model was established and clinical severity of AA was evaluated by arthritis index, paw edema, plasma, and synovium homogenate parameters. The severity of joint destruction was assessed by radiological and histopathological. Immunohistochemical analysis was employed to detect the protein expression of MMP-3, MMP-13 in synovium and cartilage tissues. The vitro effects of MF on proliferation, migration, apoptosis, and production of inflammatory mediators in RA- FLSs were determined by the CCK8 assay, transwell assay, flow cytometry, and real-time PCR, respectively. RESULTS: The results demonstrated that MF treatment significantly alleviated arthritis index, paw swelling and decreased the secretion of inflammatory cytokines in plasma and synovium. Meanwhile, MF inhibited synovial inflammation, pannus formation, and bone erosion in AA rats. It also ameliorated the oxidative stress state of arthritic rats via modulating the level of MDA, SOD, CAT, GSH, NO. In addition, MF effectively attenuated the destructive behavior of RA-FLSs by inhibiting proliferation, migration, and secretion of inflammatory mediators, and promoting apoptosis. The further mechanistic analysis demonstrated that MF might exert an antiarthritic effect via inhibiting the pathway of MAPKs (ERK2 and p38) and NF-κ B. CONCLUSION: Taken together, our results demonstrated that MF would be a promising anti-arthritic agent candidate for further research.
33180998 Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activ 2021 Feb KEY POINTS: Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved.  This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA.  Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain.  The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT: Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAP(exercise)  = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAP(PEI)  = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNA(exercise)  = 17 ± 14 vs. 7 ± 9 bursts min(-1) , P = 0.04; ΔMSNA(PEI)  = 14 ± 10 vs. 6 ± 4 bursts min(-1) , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.
34042327 Identification of Novel, Immunogenic HLA-DR-Presented Prevotella copri Peptides in Patient 2021 Dec OBJECTIVE: We previously identified HLA-DR-presented epitopes from a 27-kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA-DR-presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis. METHODS: Using tandem mass spectrometry, we searched for HLA-DR-presented Pc peptides in PBMCs from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, and the general population. These results were assessed for correlation with clinical findings. RESULTS: Including Pc-p27, we identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses, and 47 of 89 patients (53%) had IgG or IgA responses to ≥1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc-p27. Additionally, 74% of RA patients with IgA antibodies to ≥1 Pc protein had anti-citrullinated protein antibodies (ACPAs) compared with 49% of patients who lacked IgA Pc antibody responses (P = 0.05), and IgA Pc antibody levels correlated with ACPA values. CONCLUSION: The majority of the RA patients had Pc immune responses. The correlation of IgA Pc antibody responses, particularly to Pc-p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.
33360228 Systemic sclerosis overlap and non-overlap syndromes share clinical characteristics but di 2021 Feb OBJECTIVES: To screen for concomitant autoimmune disease in patients with systemic sclerosis (overlap SSc) and to describe their clinical characteristics and prognosis. METHODS: This was a two-center retrospective observational study. Patients diagnosed with SSc according to the 2013 ACR-EULAR scleroderma classification criteria were screened for concomitant rheumatoid arthritis (RA), Sjögren syndrome (SgS) and systemic lupus erythematosus (SLE). Patient characteristics were retrieved from the medical records and were compared to those of a non-overlap SSc cohort. RESULTS: Among the 534 SSc patients studied, thirty-four (6.4%) were identified as having overlap SSc. There were 21 (3.9%) patients with RA, 14 (2.6%) with SgS and 4 (0.7%) with SLE (5 patients had 2 AISD) . The disease phenotype of overlap SSc was similar to that of non-overlap SSc in terms of cutaneous phenotype, prevalence of pulmonary arterial hypertension, interstitial lung disease, digital ulcers and mortality. Using a multivariate Cox model, age (HR = 1.04, 95% CI [1.02-1.07]), the modified Rodnan skin score (HR = 1.08 per point, 95% CI [1.05-1.11]), and the presence of concomitant SgS (HR = 3.79, 95% CI [1.38-10.40]) were significantly associated with mortality. Overlap SSc were more likely to receive corticosteroids (85.3% vs. 45%, p < 0.001), immunosuppressive drugs (82.4% vs. 49.2%, p < 0.001) and biologics (52.9% vs. 3.8%, p < ZZ0.001). CONCLUSIONS: While overlap and non-overlap SSc shared common characteristics, patients with SgS/SSc had a higher risk of mortality, and those with RA/SSc received more corticosteroids, methotrexate and biologics. Screening for an associated AISD should be promoted since their co-occurrence with SSc may affect prognosis and treatments.
33703989 Effect of adalimumab interventions on general infection among adults: a systematic review 2021 Oct BACKGROUND: This study assessed the safety of adalimumab in different dosages and durations of treatment. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore the infection risk in people who received adalimumab. We searched the Cochrane Library, PubMed, and EMBASE from inception to December 8, 2020. Summary estimates were obtained  using meta-analysis with a random-effects model. RESULTS: Twenty-one RCTs, considered to be of high quality, were analyzed. We found that there was a risk of infection (RR: 1.10, 95% CI: 1.02-1.18). In the stratified analysis, we found an increase in infection among those that received normal dosage (RR: 1.13, 95% CI: 1.04-1.23), and in patients with psoriasis (RR: 1.13, 95% CI: 1.00-1.35) and rheumatoid arthritis (RR: 1.23, 95% CI: 1.06-1.41), but not in those that received high doses and other criteria. In the meta-regressions, intervention duration was not related to changes in incidence risk. CONCLUSIONS: Trials that have a longer treatment duration and higher doses are needed to clarify whether patients that received adalimumab had an elevated risk of general infection.
33679801 Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rhe 2021 Biologic drugs, especially anti-TNF, are considered as the gold standard therapy in rheumatoid arthritis. However, non-uniform efficacy, incidence of infections, and high costs are major concerns. Novel tissue-specific agents may overcome the current limitations of systemic administration, providing improved potency, and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, via the synovial-specific single-chain variable fragment (scFv)-A7 antibody, and TNFα neutralization, via the scFv-anti-TNFα of adalimumab, with the binding/blocking capacity comparable to adalimumab -immunoglobulin G (IgG). Tissue-targeting capacity of the BsAb was confirmed on the human arthritic synovium in vitro and in a synovium xenograft Severe combined immune deficient (SCID) mouse model. Peak graft accumulation occurred at 48 h after injection with sustained levels over adalimumab-IgG for 7 days and increased therapeutic effect, efficiently decreasing tissue cellularity, and markers of inflammation with higher potency compared to the standard treatment. This study provides the first description of a BsAb capable of drug delivery, specifically to the disease tissue, and a strong evidence of improved therapeutic effect on the human arthritic synovium, with applications to other existing biologics.
33940272 Staged Repositioning in Endoscopic Endonasal Odontoidectomy Maximizes Decompression While 2021 Jul BACKGROUND: Preservation of the anterior arch of C1 in endoscopic endonasal odontoidectomy has been proposed as an alternative to complete C1 arch resections, potentially affording less destabilization of the craniocervical junction. Nonetheless, this approach may limit the decompression achieved. In this case, intraoperative repositioning allowed maximal decompression while preserving the anterior arch of C1. METHODS: A 79-year-old woman presented with suboccipital pain caused by an expansile and compressive mass centered on the dens. Notably, the mass occluded both vertebral arteries resulting in small cerebellar strokes. An endoscopic endonasal approach for diagnosis and decompression was performed followed by posterior fixation. RESULTS: Given the significant compression, the patient was initially positioned in slight cervical extension. After rhinopharyngeal flap harvest, the top half of the anterior arch of C1 was resected, maintaining its structural integrity. The odontoidectomy was completed flush to the superior border of the reduced C1 arch. After an intraoperative computed tomography (CT) scan, performed in a neutral position, the patient was then repositioned with cervical flexion. This maneuver presented the residual odontoid above the C1 arch, but, given the partial removal of the dens, it did not result in any change in neuromonitoring. Further odontoid resection was then completed and follow-up CT scan revealed maximal dens removal, extending below the C1 anterior arch in neutral position. CONCLUSIONS: In cases of odontoid/atlantoaxial pathology causing significant neural compression, staged intraoperative repositioning can safely maximize the odontoidectomy, while affording preservation of the structural integrity of the anterior arch of C1.
32676896 Renal pathological analysis using galactose-deficient IgA1-specific monoclonal antibody is 2021 Feb In several cases with IgA nephropathy (IgAN), differential diagnosis is difficult due to the complication with other systemic diseases which can induce secondary IgAN. Recently, we demonstrated that immunostaining with galactose-deficient IgA1-specific monoclonal antibody (KM55 mAb) specifically showed positive in primary IgAN cases. Here, we report four cases which we could make definitive diagnosis by immunohistological analysis using KM55 mAb. The underlying systemic diseases are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), hepatitis C (HCV) and Crohn's disease (CD). Renal pathological findings in the four cases revealed mesangial proliferative glomerulonephritis with IgA and C3 deposits. Immunostaining with KM55 mAb was positive for three cases complicated with RA, SLE and CD, respectively. Thus, these three cases were diagnosed as primary IgAN and treated with tonsillectomy and steroid pulse therapy. These three cases finally achieved clinical remission. On the other hand, the case with HCV showed negative for KM55. Finally, we diagnosed as HCV-related nephropathy and successfully treated by antiviral agents. These cases suggested KM55 mAb is a strong tool to differentiate primary IgAN from secondary IgAN.
34567284 The Diagnostic Value of Synovial Fluid Lymphocytes in Gout Patients. 2021 OBJECTIVE: This study is aimed at investigating the diagnostic value of synovial fluid cell counts in gout patients. METHODS: A total of 185 gout, 64 rheumatoid arthritis (RA), 26 axial spondyloarthritis (axSpA), and 24 osteoarthritis (OA) patients were included in the study. According to serum uric acid (sUA) levels on attack, gout patients were divided into normal sUA gout patients and high sUA gout patients. The laboratory data were recorded. ROC curves were generated to evaluate the diagnostic value of the variables for gout patients and normal sUA gout patients compared with RA, axSpA, and OA patients. RESULTS: The synovial fluid white blood cell (WBC), peripheral blood mononuclear cell (PBMC), monocyte, polymorphonuclear (PMN), and neutrophil counts in gout patients were higher than those in OA patients (P < 0.05). The synovial fluid PBMC and lymphocyte counts in gout patients were lower than those in RA and axSpA patients (P < 0.05). ROC curve results showed that the AUC values of lymphocytes and sUA for gout patients were 0.728 and 0.881, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for gout was 1.362, with a Youden index of 0.439, a sensitivity of 83.3%, and a specificity of 60.6%. The AUC values of lymphocytes, sUA, and CRP for normal sUA gout patients were 0.694, 0.643, and 0.700, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for normal sUA gout patients was 1.362, with a Youden index of 0.422, a sensitivity of 81.6%, and a specificity of 60.6%. CONCLUSIONS: The synovial fluid cell counts of gout patients were different from those of RA, axSpA, and OA patients. Synovial fluid lymphocytes had a higher diagnostic value for gout.
33626115 The presence of effusions between the volar plate of the proximal interphalangeal joint an 2021 May 20 AIM: In clinical practice, an anechoic signal was often exhibited between the volar plate (VP) of the proximal interphalan-geal joint (PIPJ) (PIPJVP) and the flexor digitorum tendon (FDT) on ultrasound, which suggests the presence of effusions (PIPJVP-FDT effusions). The purpose of this study was to investigate the prevalence of PIPJVP-FDT effusions and to explore the possible mechanism preliminarily. MATERIAL AND METHODS: A single-center, cross sectional study in hand osteoarthritis (HOA) patients, rheumatoid arthritis (RA) patients and healthy controls was conducted. Ultrasound examination was per-formed by the same real-time scanner with 18-MHz linear array transducer. Bilateral interphalangeal joints (IPJs) of the thumb, 2ed, 3rd, 4th and 5th PIPJs were examined. The PIPJVP-FDT effusions was defined as an anechoic signal between the PIPJVP and FDT in two perpendicular ultrasound planes. RESULTS: In total, 200 patients with HOA, 78 patients with RA and 101 healthy controls were eligible for the study. 37.6% of healthy controls and 35.0% of HOA patients showed PIPJVP-FDT effusions, while only 11.5% of RA patients had PIPJVP-FDT effusions (p<0.001). The 2ed, 3rdand 4th PIPJs showed more PIPJVP-FDT effusions, while the IPJs of the thumbs and 5th PIPJs showed less PIPJVP-FDT effusions (p<0.05). Furthermore, the prevalence of PIPJVP-FDT effusions in different age groups were similar in HOA patients and healthy controls. CONCLUSION: To the best of our knowledge, this paper is the first to demonstrate that the presence of PIPJVP-FDT effusions is a very common phenomenon in HOA patients and healthy individuals, and may be unrelated to inflammation, degeneration and age.
33494792 A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, 2021 Jan 25 OBJECTIVE: Curcumin (CUR), vitamin D(3) (D3), and omega-3-fatty acids (O3FA) individually modulate inflammation and pain in arthritis. Although these supplements are widely used, their combinatorial effects have not been defined. In this study, we examined the effects of a D3 and O3FA (VO)-enriched diet in conjunction with a highly bioavailable form of CUR (Cureit/Acumin™) in a collagen-induced arthritis (CIA) murine model. METHODS: Male DBA/1J mice were acclimatized to VO-enriched diet and challenged with bovine collagen II (CII). Bioavailable CUR was administered daily by oral gavage from the onset of CII challenge. Disease severity was determined by monitoring joint thickness and standardized clinical score. Cellular infiltration and cartilage degradation in the joints were assessed by histology, serum cytokines profiled by Meso Scale Discovery multiplex assay, and joint matrix metalloproteinases examined by western blots. RESULTS: CUR by itself significantly decreased disease severity by ~ 60%. Administration of CUR in CIA mice taking a VO-enriched diet decreased disease severity by > 80% and maximally delayed disease onset and progression. Some of the disease-modifying effects was mediated by CUR alone, e.g., suppression of serum anti-collagen antibodies and decrease of cellular infiltration and MMP abundance in the joints of CIA mice. Although CUR alone suppressed inflammatory cytokines in serum of CIA mice, the combination of CUR and VO diet significantly enhanced the suppression (> 2-fold compared to CUR) of TNF, IFN-γ, and MCP-1, all known to be associated with RA pathogenesis. CONCLUSION: This study provides proof-of-concept that the combination of bioavailable CUR, vitamin D(3), and O3FA substantially delays the development and severity of CIA. These findings provide a rationale for systematically evaluating these widely available supplements in individuals at risk for developing future RA.
33651341 Treatment with SDZ-ADL, an Adalimumab Biosimilar, in Patients with Rheumatoid Arthritis, P 2021 Mar BACKGROUND: SDZ-ADL (GP2017; Sandoz GmbH, Austria) is an EMA-/FDA-approved adalimumab biosimilar. The effect of SDZ-ADL on quality of life (QoL) and patient-reported outcomes (PROs) was assessed as part of two phase III studies, one in patients with moderate-to-severe chronic plaque psoriasis (PsO; ADACCESS) and the other in patients with rheumatoid arthritis (RA; ADMYRA). Additionally, ADACCESS included patients with psoriatic arthritis (PsA). METHODS: ADACCESS included 465 patients with PsO, whereas ADMYRA included 353 patients with RA. Both studies evaluated and confirmed equivalent efficacy, similar safety, and immunogenicity of SDZ-ADL with reference adalimumab (ref-ADL). A third of patients underwent multiple (four) treatment switches between study treatments starting at Week 17 (ADACCESS); all patients switched from ref-ADL to SDZ-ADL at Week 24 (ADMYRA). Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in ADACCESS, Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) score in ADMYRA, and Health Assessment Questionnaire-Disability Index (HAQ-DI) in both studies. RESULTS: In both studies, baseline scores for all PRO assessments were comparable between the two treatment groups. In ADACCESS, mean DLQI decreased from baseline in both groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at Week 17 (SDZ-ADL, - 64.5 [80.3]; ref-ADL, - 70.6 [41.7]), which were sustained after the switch at Week 51 ('continued SDZ-ADL,' - 79.7 [36.2]; 'continued ref-ADL,' - 80.8 [44.6]; 'switched to SDZ-ADL,' - 70.7 [32.2]; 'switched to ref-ADL,' - 69.3 [49.6]). In ADACCESS, the proportion of patients with an EQ-5D-5L score of 1 (no problems) increased from baseline for all five dimensions in all treatment groups and was comparable between treatment groups at Week 51. In ADACCESS, in patients with PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline in both treatment groups, and scores were comparable between groups at Week 17 (SDZ-ADL, 0.5 [0.6]; ref-ADL, 0.5 [0.6]) and after switching at Week 51 ('continued SDZ-ADL,' 0.4 [0.5]; 'continued ref-ADL,' 0.4 [0.6]; 'switched to SDZ-ADL,' 0.5 [0.8]; 'switched to ref-ADL,' 0.7 [0.6]). In ADMYRA, proportion of patients achieving HAQ-DI in the normal range (≤ 0.5) was comparable between treatment groups at Week 24 (SDZ-ADL, 37.8%; ref-ADL, 36.3%) and after switching at Week 48 ('SDZ-ADL,' 41.6%; 'ref-ADL/switched to SDZ-ADL,' 40.0%). In ADMYRA, mean FACIT-Fatigue scores increased from baseline in both treatment groups. At Week 24, mean (SD) percent change from baseline in the FACIT-Fatigue scores was 75.4 (135.5) in SDZ-ADL and 73.0 (96.3) in ref-ADL groups; the scores were sustained after switching at Week 48. CONCLUSION: Treatment with SDZ-ADL and ref-ADL resulted in comparable improvements in PROs as well as QoL scores across the three diseases, PsO, PsA, and RA. Switching between SDZ-ADL and ref-ADL had no negative impact on PROs across the reported period. CLINICAL TRIALS. GOV IDENTIFIER: NCT02744755, NCT02016105.