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ID PMID Title PublicationDate abstract
30928902 Running promotes chronicity of arthritis by local modulation of complement activators and 2019 Jun OBJECTIVES: The mechanisms driving onset of joint inflammation in arthritides such as rheumatoid arthritis and spondyloarthritis and the conversion to disease chronicity are poorly understood. We hypothesised mechanostrain could play an instrumental role herein by engaging local and/or systemic pathways, thereby attenuating disease course and outcome. METHODS: The development of collagen antibody-induced arthritis (CAIA) in C57BL/6 mice was evaluated both clinically and histologically under different loading regimens: control, voluntary running or hindpaw unloading. Bone surface porosity was quantified by high-resolution µ-CT. Gene expression analyses were conducted by microarrays and qPCR on microdissected entheses, murine and human synovial tissues (both normal and inflamed). Serum cytokines and chemokines were measured by ELISA. The influence of complement activation and T regulatory (Treg) cell function on the induction and resolution phase of disease was studied by respectively pharmacological modulation and conditional Treg depletion. RESULTS: Voluntary running strongly impacts the course of arthritis by impairing the resolution phase of CAIA, leading to more persistent inflammation and bone surface porosity. Mechanical strain induced local complement activation, increased danger-associated molecular pattern expression, activating Fcγ receptors as well as changes in fibroblast phenotype. Interestingly, complement C5a receptor blockade inhibited the enhanced joint pathology caused by voluntary running. Moreover, Treg depletion led to a loss of disease resolution in CAIA mice, which was not observed under voluntary running conditions. CONCLUSIONS: Running promotes onset and chronicity of arthritis by local upregulation of complement activators and hampering regulatory T cell feedback loops.
31101752 Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheum 2020 Mar Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation and progressive destruction of joint tissue. It is also characterized by aberrant blood phenotypes including anemia and suppressed lymphopoiesis that contribute to morbidity in RA patients. However, the impact of RA on hematopoietic stem cells (HSC) has not been fully elucidated. Using a collagen-induced mouse model of human RA, we identified systemic inflammation and myeloid overproduction associated with activation of a myeloid differentiation gene program in HSC. Surprisingly, despite ongoing inflammation, HSC from arthritic mice remain in a quiescent state associated with activation of a proliferation arrest gene program. Strikingly, we found that inflammatory cytokine blockade using the interleukin-1 receptor antagonist anakinra led to an attenuation of inflammatory arthritis and myeloid expansion in the bone marrow of arthritic mice. In addition, anakinra reduced expression of inflammation-driven myeloid lineage and proliferation arrest gene programs in HSC of arthritic mice. Altogether, our findings show that inflammatory cytokine blockade can contribute to normalization of hematopoiesis in the context of chronic autoimmune arthritis.
31894057 TNF gene promoter region polymorphisms and association with young-onset rheumatoid arthrit 2019 Sep Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that shares a major global economic burden due to disabilities and mortality risk. It affects all age groups with a female predominance. Tumor Necrosis Factor (TNF) a proinflammatory cytokine is one of the key players in etiology of autoimmune diseases such as RA. TNF gene promoter polymorphisms predict disease susceptibility, severity and therapeutic response. Therefore, the current case-control study was designed to evaluate the possible association of TNF gene promoter polymorphisms (-238 and -308) with susceptibility to young-onset RA. The study involves 102 individuals (50 young-onset RA patients, 52 healthy individuals). Genomic DNA was extracted using a standard phenol-chloroform method followed by PCR-RFLP for the screening of TNF gene promoter polymorphisms (-238 and -308). The study resulted in the association of TNF -238G/A polymorphism with susceptibility to young-onset RA in the homozygous form GG (Odds Ratio = 3.23, p-value= <0.05), though no significant difference was observed for -308G/A polymorphism among young-onset RA patients and controls. Thus concludes; TNF -238/G/A contributes to the risk of susceptibility to young-onset RA, conversely, TNF -308 G/A protects against the disease. Consequently, the study has demonstrated a possible relationship of studied TNF polymorphism with young-onset RA.
30210119 Fatal Chronic Active Epstein-Barr Virus Infection in a Rheumatoid Arthritis Patient Treate 2019 Feb 15 Chronic active Epstein-Barr virus (CAEBV) T-cell type infection, systemic form, is characterized by persistent infectious mononucleosis-like symptoms, high Epstein-Barr virus (EBV) DNA levels in the peripheral blood, organ damage, and a poor prognosis. The association between CAEBV and rheumatoid arthritis (RA) is unclear. We report a case of fatal CAEBV T-cell type infection in an RA patient undergoing treatment with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein (abatacept, ABT). CAEBV can rapidly worsen in RA patients receiving ABT. Thus, we should try to establish an early diagnosis in patients with CAEBV infection.
30796319 Vitamin D Receptor Polymorphism and DHCR7 Contribute to the Abnormal Interplay Between Vit 2019 Feb 22 Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade. Vitamin D was decreased in RA (p < 0.001), correlated to HDL-cholesterol (r = 0.217, p < 0.001) and total-/HDL-cholesterol ratio (r = -0.227, p = 0.004). These correlations were restricted to the VDR-rs2228570 status. Vitamin D deficiency was associated with lower HDL-cholesterol (p = 0.028), higher tender (p = 0.005) and swollen (p = 0.002) joint counts, higher DAS28 (p = 0.018) and HAQ (p = 0.024) in AG/AA-patients but not in their GG-counterparts. The associations among DHCR7, vitamin D and lipid profile followed a seasonal pattern, decreased DHCR7 (p = 0.008) and vitamin D (p < 0.001) and increased total-cholesterol (p = 0.025) being found in winter/spring. Increasing vitamin D upon TNFα-blockade paralleled RA clinical improvement (r = -0.610, p = 0.027) and DHCR7 elevation (r = 0.766, p = 0.002). In conclusion, vitamin D-related polymorphisms and DHCR7 are pivotal to understand the complex, seasonal associations between vitamin D and lipid profile in RA.
30590784 Gender stratified adjustment of the DAS28-CRP improves inter-score agreement with the DAS2 2019 May 1 OBJECTIVES: To evaluate determinants of discordance between DAS28-ESR and DAS28-CRP and resulting impact on disease activity stratification in RA. METHODS: Paired DAS28-ESR and DAS28-CRP readings (n = 31 074) were obtained from the British Society for Rheumatology Biologics Register for RA. Factors influencing discordance between DAS28-ESR and DAS28-CRP were evaluated alongside the resulting effect on disease activity stratification. The impact of gender adjustment to the DAS28-CRP was evaluated. RESULTS: DAS28-CRP scores were ∼0.3 lower than DAS28-ESR overall, with greatest differences for women (-0.35) and patients over 50 years old (-0.34). Mean male DAS28-CRP scores were 0.15 less than corresponding DAS28-ESR scores. Discordance between DAS28-ESR and DAS28-CRP significantly impacted disease activity stratification at low disease activity and remission thresholds (32.0% and 66.6% concordance, respectively). Adjusting DAS28-CRP scores by gender significantly (P < 0.001) improved agreement with the DAS28-ESR. CONCLUSION: Discordance between DAS28-ESR and DAS28-CRP is greatest for women and patients over 50 years of age, and influences disease activity stratification. The proposed gender-adjusted DAS28-CRP improves inter-score agreement with DAS28-ESR, supporting more reliable disease activity stratification in treat-to-target approaches for RA.
31321076 Implementation and role of modern musculoskeletal imaging in rheumatological practice in m 2019 OBJECTIVES: To document the current training, implementation and role of modern musculoskeletal imaging techniques: ultrasound, magnetic resonance imaging, computed tomography and positron emission tomography, among rheumatologists in the member countries of the EULAR. METHODS: English-language questionnaires for each imaging modality developed by a EULAR task force were sent out to national and international scientific societies as well as imaging experts in the given modalities involved in research and/or training. The surveys were distributed via an online survey tool (SurveyMonkey). Simple descriptive and summary statistics were calculated from the responses. RESULTS: More than 90% of ultrasound (US) experts reported the availability of a US unit in their department. Suspicion of rheumatoid arthritis and spondyloarthritides were the main clinical indications for performing US for diagnostic purposes. Suspicion of sacroiliitis and degenerative spine disease were the most common indications to perform magnetic resonance imaging (MRI) or computed tomography (CT) for diagnostic purposes, while positron emission tomography was mainly performed to diagnose large vessel vasculitis and to investigate fever of unknown origin. The reported percentage of rheumatologists performing US was highly variable, ranging from more than 80% in 6% of countries to less than 10% in 15% of countries. The majority of experts (77%) reported that their national rheumatology societies organise musculoskeletal US courses, while courses in MRI or CT organised by the national rheumatology societies were less commonly reported (29% and 8%, respectively). CONCLUSIONS: Rheumatologists in Europe utilise modern imaging techniques; however, access to the techniques and training offered is varied.
31602898 [Progress of effect and mechanisms of Tripterygium wilfordii on immune system]. 2019 Aug Traditional Chinese medicine Tripterygium wilfordii Hook.f( TWHF) is a natural botanical drug in China. It has complex chemical compositions and has been used for a long history. TWHF was used as an insecticide to protect crops at early stage,and it was later found to have significant effects in the treatment of rheumatoid arthritis,attaining great concerns. With further researches,it was found that TWHF can treat various diseases in the medical field due to a variety of pharmacological activities such as anti-cancer,neuroprotection,anti-inflammatory and immune-suppressing,particularly. Multiple extracts of TWHF have unique immunosuppressive function,playing an immune role through multi-target and multi-channel,with significant effect in the treatment of autoimmune diseases. As an immune-suppressing drug,TWHF is worthy of in-depth research due to its broad application prospects. While achieving good clinical efficacy,reports about its toxic effects to multiple systems of the body are also increasing,greatly hindering its clinical application. In order to fully understand the immune-suppressing function of TWHF and reduce or avoid the occurrence of toxic and side effects,we summarized recent progress of TWHF on the immune organs,cells and factors in recent years,as well as the pharmacology and toxic effects,hoping to provide a scientific and reasonable reference for its wider use in clinical treatment.
31203222 Correlates of Successful Rheumatoid Arthritis Flare Management: Clinician-driven Treatment 2020 Mar OBJECTIVE: Describe strategies used to manage rheumatoid arthritis (RA) flares that contribute to a successful postflare outcome. METHODS: Data were collected from the BRASS registry, including clinical and patient-reported outcomes, and a survey with a Likert scale assessing postflare symptoms (better, unchanged, or worse). A logistic regression analysis adjusting for age, sex, flare number in the past 6 months, flare pain severity, home management, clinical consultation, and medication change was performed to evaluate factors influencing flare outcome. RESULTS: Of 503 participants, 185 reported at least 1 flare that had resolved in the past 6 months, with median (interquartile range) 28-joint count Disease Activity Score based on C-reactive protein 3 score 2.1 (1.7-2.8). Compared with RA symptoms before the flare, 22 (12%) patients felt worse, 125 (68%) were unchanged, and 38 (20%) felt better. To manage flares, 72% of patients used home-based remedies, 23% sought clinical consultation, and 56% made medication change. Of 103 patients who changed medication, 70% did so without seeking clinical advice. Making a medication change (OR 3.48, 95% CI 1.68-7.21) and having lower flare pain (OR 0.83, 95% CI 0.71-0.97) were associated with better flare outcome. CONCLUSION: Flares occur frequently even in patients with low disease activity. Independent of home-based or clinically guided care, making a medication change and having less severe pain during a flare were associated with better flare outcomes. Of interest, the decision to change medications was frequently made without clinical advice. Future studies might address how best to intervene when patients experience flares and whether patient-initiated medication changes have adverse outcomes.
30809736 Prevalence of frailty and its associated factors in patients with rheumatoid arthritis: a 2019 Jul OBJECTIVES: The aims of the present research were to assess the prevalence of frailty and its potential associated factors in a cohort of adult patients with rheumatoid arthritis (RA). METHODS: Consecutive RA patients and healthy controls were assessed according to the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI), and classified as frail, pre-frail, or non-frail. Chi-square, analysis of variance (ANOVA), and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest. RESULTS: Two hundred and ten consecutive RA patients (65.7% female, mean age 60.4 years) and 100 healthy controls (63% female, mean age 59.1 years) were included. According to SHARE-FI criteria, 35 RA patients (16.6%) were categorized as frail, 68 (32.4%) as pre-frail, and 107 (51%) as non-frail, while 8 control subjects were categorized as frail, (8%), 17 as pre-frail (17%), and 75 as non-frail (75%) (chi-squared 12.8; P = 0.0016). The results from logistic regression analysis revealed that age (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.07-1.17; P < 0.0001), comorbidities (OR = 1.51, 95% CI = 1.01-2.27; P = 0.0446), and high disease activity (OR = 1.10, 95% CI = 1.04-1.16; P = 0.0006) were independently associated with frailty in RA. CONCLUSIONS: Frailty or pre-frailty are common in RA. The SHARE-FI may be a useful tool for the screening of frailty in RA and may summarize the results of a comprehensive RA assessment providing a marker of deficits accumulation.
31593087 Combination of COX-2 inhibitor and metformin attenuates rate of admission in patients with 2019 Oct Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease associated with increased prevalence of type 2 diabetes mellitus (T2DM). Here, we investigated the effect of the combination of cyclooxygenase (COX)-2 inhibitors and metformin on the rate of admission in patients with RA and T2DM and compared it with that of only COX-2 inhibitors.In total, 1268 subjects with RA and T2DM under COX-2 inhibitor and metformin therapy were selected from the National Health Insurance Research Database of Taiwan, along with 2536 patients as 1:2 sex-, age-, and index year-matched controls without metformin therapy. Cox proportional hazard analysis was used to compare the rate of admission during the 10 years of follow-up.At the end of the follow-up, 72 enrolled subjects (1.89%) had admission, including 9 from the combination group (0.71%) and 63 from the COX-2 inhibitor group (2.48%). The combination group was associated with a lower rate of admission at the end of follow-up (P < .001). Cox proportional hazard regression analysis revealed the lower rate of admission for subjects under combination therapy (adjusted hazard ratio of 0.275; 95% confidence interval = 0.136-0.557, P < .001).Patients with RA and T2DM receiving the combination of COX-2 inhibitors and metformin were associated with lower admission rate than those on COX-2 inhibitors alone, and this effect may be attributed to the decrease in the levels of proinflammatory factors.
31309512 Assessment of Proteus mirabilis Antigen Immunological Complexes by Atomic Force Microscopy 2019 Atomic force microscopy (AFM) is being increasingly used to directly measure protein interactions in nearly physiological environments. Here, protocols for atomic force microscopy (AFM) for visualization of antigen-antibody complexes are presented. The technique is used to demonstrate complexes formed by rheumatoid arthritis patient antibodies with lipopolysaccharide (LPS) isolated from P. mirabilis (O3) strain S1959 and a synthetic antigen (LPS epitope of 6 N-alpha-(D-galacturonoyl)-L-lysine residues).
29908014 Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rh 2019 May OBJECTIVE: Randomized controlled trials (RCTs) exist along a spectrum, from explanatory, designed to evaluate interventions under ideal conditions, to pragmatic, designed to reflect usual care. This study assessed the pragmatism of RCTs of advanced therapeutics in rheumatoid arthritis (RA). METHODS: A systematic review was conducted to identify RA RCTs comparing biologic or targeted synthetic therapy in combination with methotrexate, to placebo or any other disease-modifying antirheumatic drugs (DMARDs). Trials were rated using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool in 9 domains, each rated from 1 (very explanatory) to 5 (very pragmatic). Latent class and regression analyses examined the heterogeneity in PRECIS-2 scores and the relationship to trial characteristics. RESULTS: In total, 96 trials were included. Eligibility, follow-up, and flexibility of delivery of the intervention were rated as explanatory, with mean ± SD PRECIS-2 scores of 2.0 ± 0.7, 2.0 ± 1.1, and 2.1 ± 0.7, respectively, reflecting strict inclusion criteria, intensive follow-up, and rigid protocols. Studies were rated as pragmatic in setting (3.6 ± 1.5) because many were international, multicenter trials, and in primary analysis (4.1 ± 1.3), because most used intent-to-treat analyses. In latent class analyses, 2 groups were identified; the majority (74%) were rated as explanatory for most domains assessed. These trials had larger sample sizes, were more likely to be industry-funded, and enrolled patients with higher Disease Activity Score in 28 joints and Health Assessment Questionnaire disability index scores, but were less likely to be at high risk of bias. CONCLUSION: RCTs of biologic DMARD treatment in combination with methotrexate for RA were rated as predominantly explanatory, which may affect the generalizability of trial results to clinical practice.
31881419 Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pa 2020 Mar BACKGROUND: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint. METHODS: We performed meta-analysis of gene expression microarray data from synovium, whole blood cells (WBC), peripheral blood mononuclear cells (PBMC), and CD4+ T cells from patients with RA and healthy controls in order to identify overlapping pathways, upstream regulators and potential biomarkers. We also analyzed single cell RNA-sequencing (scRNA-seq) data from peripheral blood and whole joints from a mouse model of antigen-induced arthritis. RESULTS: Analyses of two profiling data sets from synovium from RA patients and healthy controls all showed significant activation of pathways with known pathogenic relevance, such as the Th1 pathway, the role of NFAT in regulation of the immune response, dendritic cell maturation, iCOS-iCOSL signaling in T helper cells, Fcγ receptor-mediated phagocytosis, interferon signaling, Cdc42 signaling, and cytotoxic T lymphocyte-mediated apoptosis. The most activated upstream regulators included TNF, an important drug target, as well as IFN-gamma and CD40LG, all of which are known to play important pathogenic roles in RA. The differentially expressed genes from synovium included several potential biomarkers, such as CCL5, CCL13, CCL18, CX3CL1, CXCL6, CXCL9, CXCL10, CXCL13, IL15, IL32, IL1RN, SPP1, and TNFSF11. By contrast, microarray studies of WBC, PBMC and CD4+ T cells showed variable pathways and limited pathway overlap with synovium. Similarly, scRNA-seq data from a mouse model of arthritis did not support that inflammatory responses in peripheral blood reflect those in the arthritic joints. These data showed pathway overlap between mouse joint cells and synovium from patients with RA, but not with cells in peripheral blood. CONCLUSIONS: Our findings indicate a dichotomy between gene expression changes, pathways, upstream regulators and biomarkers in synovium and cell types in peripheral blood, which complicates identification of biomarkers in blood.
30565876 Association between cumulative methotrexate dose, non-invasive scoring system and hepatic 2019 Feb BACKGROUND: Methotrexate (MTX) is recommended by recent American College of Rheumatology and European League against Rheumatism guidelines as a first-line drug for rheumatoid arthritis (RA). Liver fibrosis, which occurs as a long-term side effect is of major concern. Monitoring aminotransferase and albumin is suggested in the guidelines, unfortunately this method is unreliable for detecting liver fibrosis. We try to find the association between clinical parameters, cumulative MTX dosage, liver fibrosis scoring systems and the presence of liver fibrosis assessed by transient elastography (TE; Fibroscan®). METHOD: Rheumatoid arthritis patients prescribed MTX were evaluated for liver fibrosis with TE. Two subgroups of patients were compared: non-fibrosis and fibrosis (TE > 7 kPa). Univariate and multivariate logistic regression analysis was performed to identify factors associated with liver fibrosis. RESULTS: One hundred and eight patients were recruited. Twenty-nine patients (26.8%) were classified by transient elastography as liver fibrosis cases. The multivariate analysis demonstrated statistical significance only in the association of body mass index (odds ratio [OR] = 1.22; 95% CI 1.05-1.41; P = 0.01); fatty liver (OR = 2.32; 95% CI 1.58-9.19; P = 0.02); alanine transaminase (OR = 1.04; 95% CI 1.02-1.09; P = 0.04) and cumulative MTX dosage (OR = 1.03; 95% CI 1.01-1.04; P = 0.001). CONCLUSIONS: Liver fibrosis measured with Fibroscan was associated with cumulative MTX. RA patients with metabolic syndrome including high body mass index and fatty liver, had a higher risk of MTX-induced hepatic fibrosis. RA patients with high cumulative MTX dose, especially patients with concurrent metabolic syndrome, should be cautiously monitored for liver fibrosis.
31647174 Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid 2019 Dec OBJECTIVE: Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add-on TAC therapy in RA patients with inadequate response to ABT. METHODS: Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add-on TAC therapy and were followed for longer than 24 weeks were included in this study. RESULTS: Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add-on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints - erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan-Meier analysis. Only one patient discontinued add-on TAC therapy due to an adverse event (itching sensation). CONCLUSION: This is the first report describing the efficacy and safety profile of add-on TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add-on TAC therapy is a worthwhile complementary treatment option in daily clinical practice.
30647190 MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Dise 2019 Aug OBJECTIVE: Magnetic resonance imaging (MRI) was used in a phase IIb study of baricitinib in patients with RA to support dose selection for the phase III program. METHODS: Three hundred one patients with active RA who were taking stable methotrexate were randomized 2:1:1:1:1 to placebo or once-daily baricitinib (1, 2, 4, or 8 mg) for up to 24 weeks. One hundred fifty-four patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and at weeks 12 and 24. Two expert radiologists, blinded to treatment and visit order, scored images for synovitis, osteitis, bone erosion, and cartilage loss. Combined inflammation (osteitis + 3× synovitis score) and total joint damage (erosion + 2.5× cartilage loss score) scores were calculated. Treatment groups were compared using ANCOVA adjusting for baseline scores. RESULTS: Mean changes from baseline to Week 12 for synovitis were -0.10, -1.50, and -1.60 for patients treated with placebo, baricitinib 4 mg, and baricitinib 8 mg, respectively (p = 0.003 vs placebo for baricitinib 4 and 8 mg). Mean changes for osteitis were 0.00, -3.20, and -2.10 (p = 0.001 vs placebo for baricitinib 4 mg and p = 0.037 for 8 mg), respectively. Mean changes for bone erosion were 0.90, 0.10, and 0.40 (p = 0.089 for 4 mg and p = 0.275 for 8 mg), respectively, in these treatment groups. CONCLUSION: MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4 and 8 mg. This corroborates previously demonstrated clinical efficacy of baricitinib and increases confidence that baricitinib 4 mg could reduce the radiographic progression in phase III studies. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01185353].
31885755 Effect of Moxibustion on HIF-1α and VEGF Levels in Patients with Rheumatoid Arthritis. 2019 BACKGROUND: Moxibustion has a therapeutic effect of reducing swelling and relieving pain in patients with rheumatoid arthritis (RA) but its mechanism is uncertain. OBJECTIVE: To evaluate the effect of moxibustion on serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with RA and to explore the possible mechanism of moxibustion. METHODS: This study involved 46 RA patients who had fulfilled the inclusion criteria and were randomly assigned to a treatment group and a control group in an equal ratio. The control group was treated with methotrexate or leflunomide, while the treatment group received methotrexate or leflunomide and moxibustion at ST 36 (Zusanli), BL 23 (Shenshu), and Ashi points. Patients' clinical symptoms, RA-associated serum markers, and serum levels of TNF-α, IL-1β, HIF-1α, and VEGF were compared in the two groups before and after intervention. Statistical analysis was performed using SPSS 21.0 statistical software. RESULTS: 37 of 46 RA patients eventually completed the whole treatment course. Compared with the control group, the treatment group significantly improved the clinical symptoms (P < 0.05) but with no significant differences in RA-associated serum markers (P > 0.05). There were significant differences in TNF-α and IL-1β among the groups after 8 weeks of treatment (P < 0.05). HIF-1α and VEGF were decreased in the treatment group after therapy (P < 0.05). VEGF was reduced in the control group (P < 0.05), while HIF-1α was not significantly improved (P > 0.05). The reductions of HIF-1α and VEGF in the treatment group were superior to the control group (P < 0.05). CONCLUSIONS: Moxibustion enhanced the anti-inflammatory and analgesic effects of conventional medicine and can enhance the effect of conventional medicine, downregulating HIF-1α/VEGF contents to inhibit angiogenesis.
30624170 Persistence of biological agents over an eight-year period in rheumatoid arthritis and spo 2019 Jan 1 OBJECTIVE: To calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in  patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. METHOD: Retrospective observational study that included patients affected by  rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started  treatment with biological agents between January 2009 and December 2012 and followed until December 2016. RESULTS: 132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median  retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06  months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did  not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab,  infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second  line: tocilizumab was the most persistent drug (median 22.1 months) in  rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. CONCLUSIONS: Tocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment.
32062477 The role of Chinese herbal medicine in the management of adverse drug reactions of lefluno 2020 Mar BACKGROUND: The high discontinuation rate in RA patients who use LEF might be attributed to their intolerance rather than irresponsibility. The concomitant administration of Leflunomide (LEF) with Chinese herbal medicine (CHM) provides a potential solution to preventing the adverse drug reactions (ADRs) induced by LEF during the treatment of rheumatoid arthritis (RA). PURPOSE: To investigate whether co-administration of LEF with CHM could bring in both increased therapeutic outcomes and reduced ADRs due to the framework of treatment at the level of entire body. STUDY DESIGN: The mechanism of LEF in RA treatment and the ADRs it induced was introduced based on recent papers. Reported clinical examples of CHM concurrent use with LEF was revealed to provide more evidence. The management of the ADRs caused by LEF was suggested by current researches on the concomitant therapy of CHM with LEF. RESULTS: The active ingredients, compounds and medicinal herbs all demonstrated properties in relieving toxicities and reducing ADRs when used with LEF and reported in several clinical cases. The wide application of concurrent use of CHM with LEF is however hindered by the complex pathogenesis of RA which requires further scientific grounds for diagnosis and treatment. CONCLUSION: This review introduced that the adoption of CHM is emerging as a novel strategy for the management of ADRs caused by LEF.