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ID PMID Title PublicationDate abstract
31364231 Protective effect of betulinic acid on Freund's complete adjuvant-induced arthritis in rat 2019 Sep The purpose of the experiment was to study the effects of betulinic acid (BA) on adjuvant-induced arthritis in rats. The rat model of rheumatoid arthritis (AA) was established by Freund's complete adjuvant. Arthritis index, joint pathology, toe swelling, hemorheology, related cytokines and ROCK/NF-κB signaling pathway were measured in rats. BA can significantly inhibit the arthritis index, improve joint pathology, reduce toe swelling, improve blood rheology, improve synovial cell apoptosis, and restore related cytokine negative regulation of ROCK/NF-κB signaling pathways. BA has an obvious therapeutic effect on joint inflammation of toes in AA model rats, which may be due to the regulation of ROCK/NF-κB signaling pathway.
30824919 Validity of a two-component imaging-derived disease activity score for improved assessment 2019 Mar 1 OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions. CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.
30934538 Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation. 2019 Mar 25 Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.
31645179 An update on investigations of autoimmune diseases affecting orofacial region. 2020 Autoimmune diseases are better diagnosed currently with advances in cellular immunology, molecular biology, and genetics. Clinical diagnosis of systemic and organ specific autoimmune diseases is a challenging task for the Oral physicians and the development of chairside investigation methods has not only saved the time but also cost factor. To understand patient's immune status, the clinical chair side diagnostic aids along with laboratory testing methods are necessary. Laboratory investigations have great importance in detecting, confirming and analyzing the severity, and predicting the prognosis of the autoimmune disease. This article aims to list out the diagnostic methods to diagnose autoimmune conditions and focuses on various diagnostic methods to effectively evaluate autoimmune disease of orofacial region.
31175417 Bilateral facial paralysis as a rare neurological manifestation of primary Sjögren's synd 2019 Sep Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder associated with a variety of systemic presentations. Varied neurological dysfunctions of newly diagnosed adult patients with pSS have been observed in recent years. We aimed to describe a rare case of acute bilateral facial paralysis diagnosed with pSS for the first time and review the previous studies including similar cases. A 69-year-old female, who had experienced ocular and oral dryness for more than 10 years, presented with bilateral facial palsy. Her laboratory test results showed positive anti-Ro (SSA) and anti-Ro-52 antibodies. Ophthalmic examination and test of saliva secretion verified xerophthalmia and xerostomia, respectively. Other possibilities of Lyme disease, Möbius syndrome, tumor, bilateral temporal bone fracture, Guillain-Barré syndrome, central nervous system lymphoma and HIV infection were ruled out. A diagnosis of pSS associated with bilateral facial paralysis was made. The literature review revealed one article describing a similar patient. Our case was the only one suffering from acute bilateral facial palsy without other nerve involvement. The presence of such patients reveals that pSS is an underlying cause of acute bilateral facial paralysis.
31181328 The protease systems and their pathogenic role in juvenile idiopathic arthritis. 2019 Aug Numerous proteases produced by synovial cells of arthritic joints, chondrocytes, macrophages and polymorphonuclear cells have been identified as responsible for the joint damage in rheumatoid arthritis. There are few scientific contributions aimed to identify similar mechanisms in the joints of patients with juvenile idiopathic arthritis. Recently, some mechanisms emerged, triggered by the TH17 and TH1/TH17 lymphocytes, which could shed new light on unexpected pathogenic pathways of joint damage in the JIA, mainly regarding the RANK-RANKL pathway. Other novelties are linked to the mechanisms of acidification of the synovial fluid, which create a microenvironment suitable for the extracellular activity of lysosomal enzymes. Some biological drugs currently used in the therapy of JIA can interfere with these mechanisms.
31858293 Quantifying disease activity in rheumatoid arthritis with the TSPO PET ligand (18)F-GE-180 2019 Dec 19 PURPOSE: While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using (18)F-fluorodeoxyglucose ((18)F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate (18)F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared (18)F-GE-180 uptake with that of (18)F-FDG and DCE-MRI measures of inflammation. METHODS: Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with (18)F-GE-180 and (18)F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUV(max)). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient K(trans) using Pearson correlation (r). RESULTS: PET/CT imaging with (18)F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). (18)F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09-0.31). (18)F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUV(max) vs. K(trans): r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). CONCLUSIONS: The correlations between DCE-MRI parameters and (18)F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer (18)F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.
30991730 How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patien 2019 Apr 15 Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.
30976751 Intensive management for moderate rheumatoid arthritis: a qualitative study of patients' a 2019 BACKGROUND: The TITRATE trial seeks to test whether intensive management is valuable in achieving disease remission in moderately active rheumatoid arthritis. Intensive management is a complex intervention consisting of: 1) 12 x monthly appointments, 2) tailored 'treatment support' based on motivational interviewing techniques, 3) optimised medication (including the opportunity for biologics), 4) provision of a Patient Handbook, and 5) shared treatment planning. This study aims to understand: a) patients' and practitioners' views on the feasibility and acceptability of intensive management, and b) patients' and practitioners' experience of receiving/providing intensive management. METHODS: A qualitative study, nested within a randomised controlled trial. Participants were patients (n = 15) in the intensive management arm of the trial and rheumatology practitioners (n = 16) providing the intensive management intervention, from 18/42 clinics across England. Data were collected via semi-structured interviews and analysed using thematic analysis and iterative categorization. RESULTS: Monthly appointments were largely acceptable to both groups who cited several treatment benefits (e.g. regular review of medication, practitioners built close relationships with patients). Practitioners were 'fairly confident' using the motivational interviewing techniques. Learning to pace was the most commonly reported self-management technique that patients and healthcare professionals worked on together, followed by gaining control over pain and fatigue. Practitioners liked having the option to offer biologics to patients with moderate RA. Most patients found the optimised medication (following monthly joint assessment) helpful and side-effects experienced were resolved. Variation existed in the extent to which patients engaged with the Patient Handbook and shared treatment planning, with those who did engage doing so in the early stages. CONCLUSIONS: Feedback from patient participants about the intensive management intervention was positive. They found increased medication helpful. Continuity of care with the same healthcare professional at regular intensive management sessions, and the treatment support provided, were highly rated. Feedback from practitioners indicated that intensive management training is feasible. Evidence from the interviews showed that some practitioners applied motivational interviewing techniques during standard care appointments and they would like the opportunity to address lifestyle issues with patients.
30678235 Patients with Rheumatoid Arthritis Were Associated with a Risk of Rotator Cuff Diseases. 2019 Jan 22 Rheumatoid arthritis (RA) commonly causes inflammation in the joints and periarticular structures. The association between RA and rotator cuff (RC) has been reported; however, epidemiological studies on RA and RC tendons are scant. Therefore, we investigated RC disease (RCD) risk and analyzed the effects of RA medication, steroids, and methotrexate, on the risk of RCD for patients with RA. We conducted a retrospective cohort study with a 6-year longitudinal follow-up in Taiwan. Patients who received RA diagnoses between 2004 and 2008 were enrolled in the study cohort. The non-RA control cohort comprised age- and sex-matched controls. Propensity score matching was used for other comorbidities and treatments. The hazard ratios (HRs) and adjusted HRs (aHRs) were estimated after confounders were adjusted for. Effects of steroid and methotrexate use on RCD risk were also analyzed. We enrolled 4521 RA patients (study cohort) and 22,605 matched controls. RCD incidence was 145 and 91 per 100,000 person-years in the RA and control cohorts, respectively. In the RA cohort, the crude HR for RCD was 1.62 (95% confidence interval (CI), 1.41⁻1.86, p < 0.001), and the aHR was 1.56 (95% CI, 1.36⁻1.79, p < 0.001). The methotrexate nonusers exhibited an aHR (vs. controls) of 1.61 (95% CI, 1.40⁻1.85, p < 0.001), but the methotrexate users did not have a significantly higher aHR than the controls. The steroid nonusers had an aHR (vs. controls) of 1.69 (95% CI, 1.46⁻1.96, p < 0.001), but the aHR of the steroid users was not significantly higher than the control aHR. Patients with RA had a higher risk for RCD compared with the non-RA control cohort. Steroids or methotrexate use significantly reduces the risk of RCD occurrence in patients with RA. Treatment for RCD symptoms and controlling inflammatory process are important to ensure high-quality care for patients with RA.
31848499 [Application of ultrasonography scoring system in the assessment of IgG4-related sialadeni 2019 Dec 18 OBJECTIVE: To assess the diagnostic value of salivary gland ultrasonography (SGUS) for IgG4-related sialadenitis. METHODS: Ultrasonography examination of major salivary glands was conducted for 48 IgG4-related sialadenitis patients and 50 Sjögren's syndrome patients, whose ages and disease duration were matched. The imaging features were graded using two different scoring systems (0-16 and 0-48, respectively) obtained from the grades of bilateral parotid and submandibular glands. The scores were used to further evaluate the features of salivary gland ultrasonography in IgG4-related sialadenitis and to compare them with Sjögren's syndrome patients. The association of SGUS scores of IgG4-related sialadenitis group with serological tests was analyzed. RESULTS: The mean age of IgG4-related sialadenitis group and Sjögren's syndrome group was 49.23 years and 50.44 years, respectively. The serum IgG4 level of the patients in the IgG4-related sialadenitis group was increased, with an average (9.60±6.43) g/L. And the serum IgE level was at a median of 251.5 (123.4-543.6) IU/mL. In the 0-16 system, the scores of submandibular glands of the patients in IgG4-related sialadenitis and Sjögren's syndrome were 6.0 (6.0-8.0) and 4.0 (2.0-8.0), and the scores of the total four glands were 10.0 (8.0-14.0) and 8.0 (4.0-12.0) respectively. In the 0-48 system, the scores of submandibular glands with IgG4-related sialadenitis and Sjögren's syndrome were 18.0 (14.5-20.0) and 11.0 (7.0-14.0), and the scores of the total four glands were 26.0 (18.5-34.0) and 21.5 (15.0-26.3) respectively. It suggested that in the 0-16 system and the 0-48 system, scores of submandibular glands and the total of four glands of IgG4-related sialadenitis were higher than those of Sjögren's syndrome. Meanwhile, the association analysis of 0-48 system showed a positive correlation of SGUS scores with serum IgG4, which also showed a positive correlation of SGUS scores with serum IgE in 0-16 system. CONCLUSION: Semi-quantitative ultrasonography scoring systems can evaluate and quantify the lesions of salivary glands, which can be helpful in the diagnosis and differential diagnosis of IgG4-related sialadenitis combined with the clinical manifestations, serological indicators and/or histopathological manifestations. Ultrasonography can also assess the activity of IgG4-related sialadenitis preliminarily.
32743504 Subcutaneous abatacept in rheumatoid arthritis: A real-life experience. 2019 Dec OBJECTIVES: To assess the effectiveness, safety, and drug survival of subcutaneous (SC) abatacept (ABA) in a cohort of rheumatoid arthritis (RA) patients in a real-world setting. METHODS: This was a retrospective cohort study from 2014 to 2018 in which patients with RA (1987 ACR criteria) were included. Patients were evaluated at a single rheumatology outpatient center in Bogotá, Colombia. The patients were classified according to their treatment background: biological-naïve (n = 65), switched from IV to SC ABA administration (125 mg-wk) (n = 32), and inadequate response to biological DMARD (n = 62). The primary endpoint was a change in DAS28-CRP and RAPID3 from baseline to 12 months. A linear mixed effect model was used to correlate repeated measures. Adverse events were assessed and recorded during each visit to the rheumatology center. Several Cox proportional hazard regression models were used to test if there were any differences in drug survival curves based on seropositivity for rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP). Statistical analysis was done using software R version 3.4.4. RESULTS: A total of 159 patients were included. Baseline characteristics of patients were as follows: female gender 84%, median age of 54 years (IQR 16), median disease duration 10 years (11), RF positive 96%, anti-CCP positive 89%, erosive disease 55%, median DAS28-CRP 5.0 (2), and median RAPID3 17 (10). Concomitant use of methotrexate and SC ABA monotherapy were reported at 52% and 30% respectively. Demographics and disease characteristics were similar for all groups, except for baseline DAS28-CRP, and RAPID3 in the group that switched route of administration. The interaction between time and group was significant (p = 0.0073) for RAPID3. Infections, constitutional symptoms, and headaches were the most frequent AEs. Retention rate corresponded to 60% at 48 months. The most frequent reason for drug suspension was loss of efficacy. Median time of treatment for SC ABA was 31 months (IQR 30). The only association that reached statistical significance was anti-CCP concentration [Q1-Q4] (p = 0.005). According to the Cox proportional hazard regression model, there were significant differences between survival curves for Q1 (HR 0.15; 0.03-0.64 95% CI; p = 0.0096), and Q2 (HR 0.28; 0.08-0.92 95% CI; p = 0.0363) compared to the seronegative group. CONCLUSIONS: The results showed an improvement in RA disease activity and physical function in patients under SC ABA treatment. Patients switching from IV to SC administration of ABA had lower activity and functional impairment at baseline. SC ABA demonstrated a good safety profile consistent with previously published data. Patients with baseline levels of anti-CCP antibody concentrations had better drug survival than seronegative patients.
31891116 Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are p 2019 BACKGROUND: To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. METHODS: A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Associations between serum levels of ROM, C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) at 4 and 12 weeks and the remission by DAS28-ESR and CDAI at 52 weeks were investigated. RESULTS: There were no significant differences in CRP and MMP-3 between DAS- or CDAI-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cut-off value that distinguished DAS-remission group from non-remission group was 305.5 U. Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (odds ratio: 6.067, 95% confidence interval: 1.305-28.203). CONCLUSION: Serum levels of ROM at 12 weeks during TCZ therapy may be predictive of DAS-remission at 52 weeks in patients with RA.
31867564 Use of a "critical difference" statistical criterion improves the predictive utility of th 2019 BACKGROUND: The Health Assessment Questionnaire-Disability Index (HAQ-DI) is used to assess functional status in rheumatoid arthritis (RA), but the change required for meaningful improvements remains unclear. A minimum clinically important difference (MCID) of 0.22 is frequently used in RA trials. The aim of this study was to determine a statistically defined critical difference for HAQ-DI (HAQ-DI-d(crit)) and evaluate its association with therapeutic outcomes. METHODS: We retrospectively analyzed data from adult German patients with RA enrolled in a multicenter observational trial in which they received adalimumab therapy at the decision of the treating clinician during routine clinical care. The HAQ-DI-d(crit), defined as the minimum change that can be reliably discriminated from random long-term variations in patients on stable therapy, was determined by evaluating intra-individual variation in patient scores. Other outcomes of interest included Disease Activity Score-28 joints and patient-reported pain and fatigue. RESULTS: The HAQ-DI-d(crit) was calculated as an improvement (decrease) from baseline of 0.68 in a discovery cohort (N = 1645) of RA patients on stable therapy and with moderate disease activity (mean DAS28 [standard deviation] of 4.4 [1.6]). In the full patient cohort (N = 2740), 22.1% of patients achieved a HAQ-DI-d(crit) improvement at month 6. Compared with patients with a small improvement in HAQ-DI (decrease of ≥0.22 to < 0.68) or no improvement (< 0.22), patients achieving a HAQ-DI-d(crit) at month 6 had better therapeutic outcomes at months 12 and 24, including stable functional improvements. Change in pain was the most important predictor of HAQ-DI improvement during the first 6 months of therapy. CONCLUSIONS: A HAQ-DI-d(crit) of 0.68 is a reliable measure of functional improvement. This measure may be useful in routine clinical care and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01076205. Registered on February 26, 2010 (retrospectively registered).
31354478 Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Trad Background: Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies. Methods: RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis. Results: Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients. Conclusion: Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.
30972151 Tumor Necrosis Factor Inhibitor Therapy and the Risk for Depression Among Working-Age Adul 2019 Feb BACKGROUND: Individuals with rheumatoid arthritis (RA) are at high risk for depression because of the overall burden of systemic inflammation. Although some evidence suggests that treatment with powerful anti-inflammatory drugs, such as tumor necrosis factor (TNF) inhibitors, may be effective in reducing the risk for depression in patients with RA, it is unclear whether such reduction in risk is dependent on the response to TNF inhibitor therapy. OBJECTIVE: To evaluate the association between the response to TNF inhibitor therapy and the risk for depression among working-age adults with RA. METHOD: This retrospective, observational cohort study design was based on data derived from commercial claims data in the QuintilesIMS Real World Data Adjudicated Claims database between October 1, 2009, and September 30, 2015. A total of 4222 working-age adults (18-62 years) with RA who started treatment with TNF inhibitor therapy and were continuously enrolled during the 3 observation periods (ie, 1-year baseline, 1-year treatment, and 1-year follow-up periods) were included in the study. Treatment response to a TNF inhibitor was measured using prescription drug claims based on a published validated algorithm. Multivariable logistic regression was used to examine the association between treatment response to TNF inhibitor therapy and the risk for depression, after controlling for baseline demographic characteristics, clinical characteristics, and RA-related medication use. An inverse probability of treatment weighting technique was used to control for observable differences in TNF inhibitor responders' characteristics versus TNF inhibitor nonresponders. RESULTS: Overall, 359 (8.5%) patients with RA had depression during the follow-up period and 1679 (39.8%) patients responded to TNF inhibitor treatment during the 1-year treatment period. A significantly lower percentage of TNF inhibitor responders (7.1%, N = 119) had depression than TNF inhibitor nonresponders (9.4%, N = 239). After controlling for other risk factors, responders to TNF inhibitors were 20% less likely to have depression during the follow-up period (adjusted odds ratio, 0.80; 95% confidence interval, 0.64-0.98) than nonresponders to TNF inhibitor therapy. CONCLUSION: The risk for depression was significantly reduced among patients with RA who responded to TNF inhibitor therapy compared with those who did not respond to such therapy. To determine whether the lower rate of depression observed with TNF inhibition is a direct effect of treatment with a TNF inhibitor, or whether it could be attributed to improvement in RA disease secondary to treatment, future studies need to also incorporate a control population of patients with RA who receive other antirheumatic regimens, such as disease-modifying antirheumatic drugs.
31508200 Recent advances in the search for a targeted immunomodulatory therapy for primary Sjögren 2019 Primary Sjögren's syndrome is a chronic autoimmune disease characterized by salivary and lacrimal gland dysfunction, leading to substantial morbidity and reduced quality of life. Many patients with primary Sjögren's syndrome also have extraglandular systemic complications, some of which can be organ- or life-threatening. Over the last decade, numerous targeted immunomodulatory therapies for primary Sjögren's syndrome have failed to show a benefit in clinical trials, and as yet no disease-modifying therapy has been approved for this disease. Herein, we provide an updated review of the clinical trial landscape for primary Sjögren's syndrome and the numerous efforts to move the field forward, including the development of new classification criteria and outcome measures, the results of recent clinical trials in this field, the challenges faced in the search for effective therapies, and the expanding pipeline of novel therapies under development.
31813070 Arthritis in Idiopathic Inflammatory Myopathies. 2019 Dec 7 PURPOSE OF REVIEW: Arthritis is a well-recognized symptom of idiopathic inflammatory myopathies (IIM). We provide a summary of available data regarding the epidemiology, clinical characteristics, and autoantibody associations of joint involvement in various forms of IIM. RECENT FINDINGS: Arthritis is reported in 18-55% of patients with IIM. It is particularly frequent (20-70%) in those with antisynthetase syndrome (ASS); highest prevalence is associated with anti-Jo-1 positivity. Most common manifestation is non-erosive polyarthritis. X-ray erosions may be found occasionally in ASS, particularly in patients with overlap with rheumatoid arthritis (RA). Arthritis is often present at the time of IIM diagnosis and it may even precede the onset of muscle weakness. Arthritis may in some cases be the main disease manifestation responsible for the disease burden in patients with IIM. Arthritis is a frequent symptom of IIM. Polyarthritis of small joints of the hands is the most frequent clinical manifestation. Arthritis may be the first or dominant symptom in IIM and therefore patients may be initially misdiagnosed as having RA. Particularly in seronegative RA patients with interstitial lung disease or Raynaud's phenomenon, the possibility of IIM should be considered.
31205465 Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Mo 2019 Dysregulated autophagy leads to autoimmune diseases including rheumatoid arthritis (RA). Arsenic trioxide (ATO) is a single agent used for the treatment of acute promyelocytic leukemia and is highly promising for other malignancies but is also attractive for RA, although its relationship with autophagy remains to be further clarified and its application optimized. For the first time, we report a defective functional module of autophagy comprising the Vitamin D receptor (VDR), PPAR-γ, microtubule-associated protein 1 light-chain 3 (LC3), and p62 which appears in RA synovial fibroblasts. ATO alleviated RA symptoms by boosting effective autophagic flux through significantly downregulating p62, the inflammation and catabolism protein. Importantly, low-dose ATO synergizes with Vitamin D in RA treatment.
31195707 GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patient 2019 Jun 5 BACKGROUND: GADD45 genes are stress sensors in response to cellular stress response, activated signal pathways leading to the stimulation of inflammatory cytokines. This study is to examine the associations of GADD45a and GADD45b genes with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. METHODS: 230 patients of RA, 140 patients of SLE, and 191 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan assay. RNA expression was quantitated with real-time polymerase chain reaction. RESULTS: The RNA expression of the GADD45b gene was significantly lower in RA patients than the control cases (p = 0.03). The odds ratio of GADD45a genotype -589 CC (rs581000) was significantly low (OR = 0.36, 95% CI, 0.15-0.87) in DR4-negative RA patients. The odds ratio of GADD45b genotype -712CT (rs3795024) in DR4-negative RA patients was 0.41 (95% CI, 0.18-0.95). In clinical manifestation, the odds ratio of GADD45b -712CT genotype with anti-RNP antibody was 4.14 (95% CI, 1.10-15.63) in SLE patients. GADD45a genotype -589GG+GC was associated with rheumatoid factor (RF) in SLE patients. CONCLUSIONS: Genotypes GADD45a -589CC and GADD45b -712CT were shown to be less susceptible to RA and related to the disease state in SLE patients.