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ID PMID Title PublicationDate abstract
29273217 Characterizing Autoimmune Disease-associated Diffuse Large B-cell Lymphoma in a SEER-Medic 2018 Feb BACKGROUND: Severe immune dysregulation such as seen in autoimmune (AI) disease is known to act as a significant risk factor for diffuse large B-cell lymphoma (DLBCL). However, little is known about the demographics or clinical outcomes of DLBCL that arises in the setting of AI disease. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for patients with a diagnosis from 1999 to 2009 linked to their Medicare claims data through 2011 to characterize the presentation, treatment, and survival patterns in DLBCL patients, including those with rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren syndrome, and other B-cell-mediated AI diseases. We examined the baseline clinical characteristics for patients with B-cell-mediated AI disease, plotted the overall survival and lymphoma-related survival (LRS) for these groups, and compared the median survival times. RESULTS: Patients with DLBCL and AI disease were more commonly female. However, patients with DLBCL and rheumatoid arthritis, SLE, Sjögren syndrome, or other B-cell AI diseases did not differ from other DLBCL patients in any other baseline presenting features and received similar first-line treatment. A trend toward decreased LRS was seen in patients with SLE and DLBCL compared with all other groups, but this difference was not statistically significant in this cohort. CONCLUSION: In the present retrospective claims-based cohort of older patients with DLBCL, concomitant AI disease was uncommon and was more likely to occur in female DLBCL patients, which likely reflects the greater incidence of AI disease in women. The possibility of lower LRS for SLE patients should be explored in future studies.
29104161 Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheuma 2018 Apr Relatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96). Incident nonalcoholic fatty liver disease was highest in patients with PsO prescribed an ST (2.23) and PsA with an ST (2.11). The risk of cirrhosis was highest among patients with PsO with an ST (2.62) and PsA without an ST (3.15). Additionally, the prevalence of liver disease and cirrhosis increased in a stepwise fashion with increasing body surface area affected by PsO (P for trend <0.001). More so than RA, PsO and PsA are associated with liver disease, particularly nonalcoholic fatty liver disease and cirrhosis, and this was true even among patients without ST exposure.
28626189 Successful Switch to Golimumab for Eosinophilia and Skin Symptoms Related to Multiple Biol 2017 Biologics used in the treatment of rheumatoid arthritis (RA) rarely cause eosinophilia. We herein report a patient with RA being treated with infliximab, adalimumab, and tocilizumab who developed eosinophilia with skin symptoms. Interestingly, the marked eosinophilia and skin symptoms did not reappear after the patient's medication was switched to golimumab. In this case, the presence of biologics-specific antibodies suggested that immunogenicity caused the eosinophilia. Therefore, switching to a biologic with a lower immunogenicity was effective. These findings may be helpful for clinicians treating patients with biologics-induced eosinophilia.
28391430 Why does total elbow arthroplasty fail today? A systematic review of recent literature. 2017 Jun BACKGROUND: Total elbow arthroplasty is a relatively uncommon type of arthroplasty, which has undergone several design changes in the past four decades. However, research on improvement requires knowledge of failure mechanisms that can be addressed. Therefore, we conducted a systematic review on modes of failure of total elbow arthroplasty. METHODS: We conducted searches on PubMed/Medline, Embase and Cochrane databases to identify studies describing modes of failure of primary total elbow arthroplasties. The results were coupled per type of total elbow arthroplasty and individual arthroplasty models. RESULTS: A total of 70 articles were included in this systematic review. 9308 individual total elbow arthroplasties were identified with 1253 revisions (13.5%). Aseptic loosening was the most prevalent reason for revision (38%), followed by deep infection (19%) and periprosthetic fractures (12%). CONCLUSION: Revision rates have been found similar to a systematic review published in 2003. The revision percentage of total elbow arthroplasty for rheumatoid arthritis is significantly higher than for trauma and post-traumatic osteoarthritis. Aseptic loosening was seen less in linked implants. Infections and periprosthetic fractures did not differ between linkage design groups. Aseptic loosening remains the most frequent cause for revision of primary total elbow arthroplasty. Therefore, more research on the occurrence, progression and risk factors of aseptic loosening should be performed and lead to higher implant survival.
28258768 Quality assessment of websites providing educational content for patients with rheumatoid 2017 Jun OBJECTIVE: We performed an environmental scan of currently available websites providing educational information about rheumatoid arthritis (RA) and evaluated the quality of these websites. METHODS: We searched three separate search engines, Google, Bing, and Ask.com, on August 27, 2015, using two search terms, "arthritis" and "rheumatoid." Only patient education websites were included. Two independent investigators evaluated the accuracy, completeness, technical elements, design and esthetics, readability, usability, and accessibility of the websites. The navigation experience was also evaluated by an adult training expert. RESULTS: We identified 46 websites. Nearly all websites (98%) provided accurate information. However, no website covered all essential RA topics. Common essential topics not covered included epidemiology, pathogenesis, treatment and disease monitoring, complications, self-management, risks and benefits of treatment, prognosis, treatment adherence, questions for patients to ask their doctors, and costs. For the technical elements, all websites disclosed their ownership, but the date that the content was last updated was mentioned in only 10 websites, ranging from 2007 to 2015. The mean reading level was grade 12.1 (standard deviation ±2.3). Most websites (78%) were easy to navigate but only 33% were friendly for people with visual and/or hearing impairments. The navigation experience was rated fair or poor in 41% of the websites. CONCLUSION: Current patient information on the Internet does not comprehensively address all educational needs of patients with RA, and is often outdated. The findings from our study highlight potential areas for improvement in online education materials for patients with RA.
28765250 Validating Rheumatoid Arthritis Remission Using the Patients' Perspective: Results from a 2017 Dec OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) working group on the patients' perspective on remission in rheumatoid arthritis (RA) has been working on this topic since 2010. At OMERACT 2016, progress and preliminary data on validity of measurement instruments for pain, fatigue, and independence in remission in RA were presented, and future directions were explored. METHODS: A special interest group was organized, in which the current data on the patients' perspective on remission were presented. The ongoing study that aimed to validate measurement instruments for pain, fatigue, and independence in a state of low disease activity or remission was presented, and preliminary data on construct validity and discriminative capacity were evaluated cross-sectionally. RESULTS: At OMERACT 2016, the progress of the working group and preliminary data from 142 of the anticipated 300 patients were presented. Selected instruments significantly correlated with the Disease Activity Score in 28 joints (construct validity) and all instruments except 1 discriminated between patients in and patients not in remission. The subsequent discussion mainly focused around 3 points: (1) the formulation of patient perceived remission, (2) the duration of remission, and (3) the measurement of the domain independence. An informal vote indicated a slight preference for working toward modifying the current remission criteria by adding patient-reported outcomes (PRO), or by substituting the patient's global assessment with 1 or more PRO. CONCLUSION: More evidence on measuring patients' perspective on remission in RA is needed before an informed decision can be made regarding development or modification of remission definitions.
27495116 Upregulated expression of CCR3 in rheumatoid arthritis and CCR3-dependent activation of fi 2017 Feb It is recognized that CC chemokine receptor 3 (CCR3) is associated with numerous inflammatory conditions and fibroblast-like synoviocyte (FLS) invasiveness correlates with articular damage in rheumatoid arthritis (RA). However, little is known of the expression and action of CCR3 on FLS in RA. In the present study, we investigated the expression of CCR3 on dispersed synovial tissue and peripheral blood cells in RA and influence of eotaxin-1 on FLS functions by using flow cytometry analysis, FLS challenge, and real-time PCR techniques. The results showed that approximately 7.0 % dispersed synovial cells are CCR3+ cells. Among those CCR3+ cells, 38.1, 23.8, and 20.6 % cells are CD90+CD14-CD3- (representing FLS), CD14+, and CD8+ cells, respectively, indicating that FLS is one of the major populations of CCR3+ cells in the synovial tissue of RA. In peripheral blood, CD14+ CCR3+ cells are elevated, but CD8+CCR3+ cells are reduced in RA. It was found that eotaxin-1 induced upregulated expression of CCR3 and matrix metalloproteinase (MMP)-9 messenger RNAs (mRNAs) in FLS. Since an antagonist of CCR3 suppressed the action of eotaxin-1, the event appeared CCR3 dependent. Moreover, we observed that interleukin (IL)-1β induced markedly enhanced eotaxin-1 release from FLS, but TNF-α reduced eotaxin-1 release at 12 and 24 h following incubation. In conclusion, enhanced expression of CCR3 on synovial cells and increased levels of eotaxin-1 in plasma and synovial fluid (SF) of RA indicate that CCR3-mediated mechanisms may play an important role in RA. Blockage of eotaxin-1 provoked CCR3 and MMP-9 expression in FLS by antagonist of CCR3, implicating that anti-CCR3 agents may have therapeutic use for RA.
28810805 Hindfoot Arthritis Progression and Arthrodesis Risk After Total Ankle Replacement. 2017 Nov BACKGROUND: The purpose of this study was to assess the radiographic progression of subtalar and talonavicular degenerative joint disease in a series of patients who had undergone TAA (total ankle arthroplasty) with minimum follow-up of 5 years. METHODS: TAA patient radiographs from a single institution were analyzed for peritalar arthritic changes by extrapolating the modified Kellgren Lawrence (KL) grades of the knee to the subtalar and talonavicular joints. Patients were included if they had a minimum of 5 years of follow-up. Patients who had undergone prior arthrodesis of the talonavicular or subtalar joints were excluded. A total of 140 patients with average follow-up of 6.5 years (range, 5.0-8.9 years) were included. RESULTS: Overall, 27% of patients advanced 1 KL grade at the subtalar joint and 31% of patients increased 1 KL grade at the talonavicular joint. Furthermore, 60% and 66% of patients showed no progression in the subtalar and talonavicular joints, respectively. Two patients progressed greater than 2 KL subtalar arthritis grades and only 2 patients with talonavicular arthritis progressed to the same extent. Sixteen patients went on to require a subtalar arthrodesis compared to 2 requiring a talonavicular fusion ( P < .05). CONCLUSION: This study suggests a moderate but nominal radiographic increase in adjacent subtalar and talonavicular arthritis over a minimum of 5 years after TAA. Future studies require a comparative control group of ankle fusion, but these data may suggest the motion preserved with an arthroplasty diminishes the stresses and compensatory motion incurred during tibiotalar arthrodesis. LEVEL OF EVIDENCE: Level IV, retrospective case series.
28472734 Comparative in silico analyses of Cannabis sativa, Prunella vulgaris and Withania somnifer 2017 Jun From last decade, there has been progressive improvement in computational drug designing. Several diseases are being cured from different plant extracts and products. Rheumatoid Arthritis (RA) is the most shared disease among auto-inflammatory diseases. Tumour necrosis factor (TNF)-α is associated with RA pathway and has adverse effects. Extensive literature review showed that plant species under study (Cannabis sativa, Prunella vulgaris and Withania somnifera) possess anti-inflammatory, anti-arthritic and anti-rheumatic properties. 13 anti-inflammatory compounds were characterised and filtered out from medicinal plant species and analysed for RA by targeting TNF-α through in silico analyses. By using ligand based pharmacophore generation approach and virtual screening against natural products libraries we retrieved twenty unique molecules that displayed utmost binding affinity, least binding energies and effective drug properties. The docking analyses revealed that Ala-22, Glu-23, Ser-65, Gln-67, Tyr-141, Leu-142, Asp-143, Phe-144 and Ala-145 were critical interacting residues for receptor-ligand interactions. It is proposed that the RA patients should use reported compounds for the prescription of RA by targeting TNF-α. This report is opening new dimensions for designing innovative therapeutic targets to cure RA.
29105466 [Effect of Warm Needle Moxibustion Intervention on Knee-joint Swelling and Expression of S 2017 Oct 25 OBJECTIVE: To observe the effect of warm needle moxibustion (WNM) on knee-joint swelling and expression of sirtuin 1 (SIRT 1, a class Ⅲ histone/protein deacetylase) and nuclear factor κB (NF-κB) in synovial tissue in rats with rheumatoid arthritis (RA). METHODS: Fifty SD rats were randomly divided into five groups:normal control, model, SIRT 1-inhibitor, WNM, and SIRT 1-inhibitor plus WNM (inhibitor+WNM), n=10 rats in each group. The RA model was established by subcutaneous injection of bovine type Ⅱ collagen at the sole, once daily for 21 days. The WNM was applied to bilateral "Zusanli" (ST 36), "Shenshu" (BL 23) and "Xuanzhong" (GB 39) for 15 min, once daily for 21 days, beginning on the 1(st) day of modeling. For rats of SIRT 1-inhibitor group and inhibitor+WNM group, nicotinamide solution (10 mmol·kg(-1)·d(-1)) was injected intraperitoneally on the 1(st), 7(th), 14(th) and 21(th) days of modeling. The swelling volume of the affected knee-joint was measured by water drainage method. The contents of IL-1 β, IL-6 and IL-8 in the serum were measured by radioimmunoassay. The expression of SIRT 1 and NF-κB p 65 proteins in the synovial tissue of knee-joint were detected by immunoblotting. RESULTS: After modeling, the knee-joint volume, serum IL-1 β, IL-6 and IL-8 contents, and the expression of NF-κB p 65 protein in synovial tissue of knee-joint were considerably increased relevant to the normal control group (P<0.01), while the expression of synovial SIRT 1 protein was significantly down-regulated (P<0.01). Following WNM intervention, the volume of the knee-joint, serum IL-1 β, IL-6 and IL-8 contents and synovial NF-κB p 65 expression were significantly decreased relevant to the model group (P<0.05), and the down-regulated expression of SIRT 1 protein was notably suppressed (P<0.05). No significant difference was found between the WNM and inhibitor+WNM groups in the knee-joint swelling degree (P<0.05). The contents of serum IL-1 β, IL-6 and IL-8, and the expression of synovial NF-κB p 65 protein of the WNM group were significantly lower than those in the inhibitor+WNM group (P<0.05), while the expression level of SIRT 1 protein was evidently higher than that in the inhibitor+WNM group (P<0.05), suggesting the effects of WNM in down-regulating serum inflammatory cytokines and NF-κB p 65 expression, and in up-regulating SIRT 1 expression after administration of SIRT 1 inhibitor. CONCLUSIONS: Warm needle moxibustion can relieve inflammatory reactions of RA rats, which may be associated to its effect in modulating SIRT 1/NF-κB p 65 signaling in the synovial tissue.
28229811 Patient phenotypes in fibromyalgia comorbid with systemic sclerosis or rheumatoid arthriti 2017 May OBJECTIVES: Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). METHODS: Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools. RESULTS: FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM. CONCLUSIONS: The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.
28698901 Circulating osteoprotegerin levels are elevated in rheumatoid arthritis: a systematic revi 2017 Oct This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA), as well as the potential influential factors. Research related to plasma/serum OPG levels in RA patients and healthy controls were gathered using PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I (2), and publication bias was evaluated using a funnel plot and Egger's linear regression test. After searching databases, 443 articles were obtained, and 11 studies with 710 RA patients and 561 controls were finally included. Meta-analysis revealed that, compared with the control group, the OPG level was significantly higher in the RA group (P < 0.001), with the SMD of 1.02 and 95%CI (0.20, 1.84). Subgroup analyses showed that race, disease duration, body mass index (BMI), and disease activity score based on the assessment of 28 joints (DAS28) were positively associated with OPG level in RA patients. Our meta-analysis revealed a significantly higher circulating OPG level in RA patients, and it was influenced by race, disease duration, BMI, and DAS28.
28620917 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guidel 2017 Aug OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.
28493323 Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patie 2017 Aug OBJECTIVE: To characterize the specific structural properties of the erosion-prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA). METHODS: In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral quantitative computed tomography (HR-pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution. RESULTS: Investigation by HR-pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P < 0.001), with 20-49-year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion-prone radial side of the joint. CONCLUSION: CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA.
28199814 Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. 2017 Feb 16 BACKGROUND: Baricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis. METHODS: We conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti-tumor necrosis factor α monoclonal antibody) every other week. End-point measures evaluated after adjustment for multiplicity included 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) (the primary end point), the Disease Activity Score for 28 joints (DAS28), the Health Assessment Questionnaire-Disability Index, and the Simplified Disease Activity Index at week 12, as well as radiographic progression of joint damage as measured by the van der Heijde modification of the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating greater structural joint damage) at week 24. RESULTS: More patients had an ACR20 response at week 12 with baricitinib than with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary objectives were met, including inhibition of radiographic progression of joint damage, according to the mTSS at week 24 with baricitinib versus placebo (mean change from baseline, 0.41 vs. 0.90; P<0.001) and an increased ACR20 response rate at week 12 with baricitinib versus adalimumab (70% vs. 61%, P=0.014). Adverse events, including infections, were more frequent through week 24 with baricitinib and adalimumab than with placebo. Cancers were reported in five patients (two who received baricitinib and three who received placebo). Baricitinib was associated with reductions in neutrophil counts and increases in levels of creatinine and low-density lipoprotein cholesterol. CONCLUSIONS: In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358 .).
29042358 Safety, immunogenicity and efficacy after switching from reference infliximab to biosimila 2018 Feb OBJECTIVES: Efficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2. METHODS: Patients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78. RESULTS: Efficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%-69.4% with INF/INF and 65.6%-68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively. CONCLUSIONS: The efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2. TRIAL REGISTRATION NUMBER: NCT01936181; EudraCT number: 2012-005733-37.
28054948 rs657075 (CSF2) Is Associated with the Disease Phenotype (BAS-G) of Ankylosing Spondylitis 2017 Jan 3 Ankylosing spondylitis (AS) is a systemic autoimmune disease mainly affecting the lumbar spine and sacroiliac joints, and exhibits peripheral inflammatory arthropathy. More than 25 loci have been identified as associated with AS. Because both AS and rheumatoid arthritis (RA) are autoimmune diseases that may share some common genetic factors, we therefore examined if the newly identified RA genetic polymorphisms were associated with AS in a Taiwanese population. In this study, we enrolled 475 AS patients and 11,301 healthy subjects from a Taiwanese biobank as controls. Although none of single-nucleotide polymorphisms (SNPs) were associated with the susceptibility to AS, the AS disease index Bath AS Global (BAS-G) clinical phenotype was observed as significantly correlated to the AA genotype of rs657075 (CSF2). The significance remains after gender/age/disease duration adjustment and after group categorization by human leukocyte antigen-B 27 (HLA-B27) genotype. We further investigated the possible functions of rs657075 through bioinformatics approaches. Results revealed that polymorphism of rs657075 is able to influence the expression of acyl-CoA synthetase long-chain family member 6 (ACSL6). In conclusion, our study indicated that rs657075 (CSF2) is strongly associated with the AS disease index Bath AS Global (BAS-G) clinical phenotype.
28882619 Variable domain glycosylation of ACPA-IgG: A missing link in the maturation of the ACPA re 2018 Jan Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations. These occurrences are indicative of an expansion of the citrulline-specific B cell response, though ACPA remain of low avidity even in established disease. This persistence of low avidity is puzzling, as the typical signs of maturation of the immune response seem to be uncoupled from the classical process of affinity maturation. In fact, it suggests that B cells expressing ACPA could bypass selection mechanisms that otherwise control the expansion of auto-reactive B cells. In the established, chronic phase, we recently found that ACPA-IgG are extensively glycosylated in the variable (Fab) domain. More than 90% of ACPA-IgG molecules carry Fab glycans that are highly sialylated. This molecular feature is striking and may provide a missing link in our understanding of the maturation of the ACPA immune response. This review, therefore, describes the current knowledge about ACPA Fab glycosylation in the pathogenesis of RA.
28259936 The tripartite motif-containing protein 3 on the proliferation and cytokine secretion of 2017 Apr Recent studies have revealed fibroblast-like synoviocytes (FLS) as a pivotal effector cell in the inflamed joint of rheumatoid arthritis (RA) patients. FLS exhibit high proliferation rates and constitutive expression of cytokines, contributing to the pathogenesis of RA. In this study, we found that the expression of tripartite motif-containing protein 3 (TRIM3), a candidate tumor suppressor gene, was lower in synovial tissue samples of RA patients than in that of healthy controls. We then investigated the role of TRIM3 on the proliferation and cytokine secretion of primary cultured FLS from RA patients. Enforced expression of TRIM3 in RA FLS led to significantly decreased cell proliferation as indicated by Cell Counting Kit-8 assay, reduced secretion of tumor necrosis factor-α (TNF)-α, interleukin (IL)-1β and IL-6 as indicated by enzyme-linked immunosorbent assays, and decreased p38 phosphorylation as assessed by western blot analysis. The proteins promoting cell cycles (cyclin D1 and PCNA) were downregulated and the protein negatively regulating cell cycle progression (p53 and p21) was upregulated after TRIM3 overexpression. Importantly, TRIM3 knockdown had reverse effects on cell proliferation, which was suppressed by the p38-specific inhibitor SB203580. In conclusion, the current results demonstrated the downregulation of TRIM3 expression in RA synovial tissues. Importantly, TRIM3 exerted an anti-proliferation role in RA FLS via p38 signaling pathway.
27312466 Efficacy and safety of methotrexate plus certolizumab pegol or placebo in active rheumatoi 2017 Aug OBJECTIVES: This study aimed to assess the relative efficacy and safety of certolizumab pegol (CZP) 200 and 400 mg + methotrexate (MTX) compared to placebo + MTX in patients with active rheumatoid arthritis (RA). METHODS: We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of CZP 200 and 400 mg + MTX and placebo + MTX (MTX group) in patients with active RA despite receiving MTX or a disease-modifying antirheumatic drug (DMARD). RESULTS: Six RCTs (30349 patients) met the inclusion criteria. The ACR20 response rate was significantly higher in the CZP 200 and 400 mg + MTX group than in the MTX group (OR 7.30, 95 % credible interval [CrI] 3.31-16.92 and OR 5.48, 95 % CrI 2.98-10.30, respectively). CZP 400 mg + MTX tended to be more efficacious than CZP 200 mg + MTX (OR 1.33, 95 % CrI 0.61-2.97). A surface under the cumulative ranking curve (SUCRA)-based ranking probability indicated that CZP 400 mg + MTX had the highest probability of achieving the ACR20 response rate, followed by CZP 200 mg + MTX and MTX (SUCRA = 0.9007, 0.7156, and 0.0002, respectively). The ACR20, 50, and 70 response rate distributions were comparable. However, the safety based on the number of adverse event (AE)-related withdrawals did not differ significantly among the three interventions. CONCLUSIONS: CZP, at dosages of 200 and 400 mg, in combination with MTX, was the efficacious intervention for active RA without causing a significant risk of AE-related withdrawals.