Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28939234 Persistence of biologic disease-modifying antirheumatic drugs in patients with rheumatoid 2018 Feb OBJECTIVES: This study examined and compared the persistence of adalimumab, etanercept, infliximab, or abatacept as first- and subsequent-line treatment for rheumatoid arthritis in the South Korean clinical practice. METHODS: We conducted a retrospective cohort study with patients receiving adalimumab, etanercept, infliximab, or abatacept between July 1, 2009 and December 31, 2012, using the nationwide Korean National Health Insurance database. Patients who were receiving a newly initiated biologic treatment and those who switched from other biologic treatment were identified and classified into first- and subsequent-use cohorts, respectively. Treatment patterns during the 1-year after treatment initiation were measured as persistence, and discontinuation including restarting, switching, and stopping. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for discontinuation of biologic treatments. RESULTS: We identified 4114 patients for the first-use cohort and 992 patients for the subsequent-use cohort. Treatment persistence with adalimumab, etanercept, and infliximab was observed in 52.5%, 56.1%, and 52.6% of the patients, respectively, in the first-use cohort, without significant differences in duration of persistence among the treatments according to the Cox proportional hazard model. In the subsequent-use cohort, treatment persistence with adalimumab, etanercept, infliximab, and abatacept was observed in 45.7%, 58.5%, 43.0%, and 60.4% of the patients, respectively. The Cox proportional hazard model found that the patients who were receiving etanercept (HR = 0.68, 95% CI: 0.52-0.88) and abatacept (HR = 0.53; 95% CI: 0.37-0.74) were significantly less likely to discontinue the treatment than those who were receiving infliximab. CONCLUSIONS: Adalimumab, etanercept, and infliximab had similar levels of persistence during the 1-year after treatment initiation, when used as first-line treatment. However, when used as a subsequent-line treatment, etanercept and abatacept had higher persistence than infliximab or adalimumab. Persistence could be a consideration when selecting the subsequent-line biologic treatment for patients with rheumatoid arthritis in South Korea.
28551175 Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administere 2019 Jan OBJECTIVE: To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. MATERIAL AND METHODS: Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. RESULTS: Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). CONCLUSIONS: In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy.
27586879 Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extensi 2017 Mar OBJECTIVES: This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX). METHODS: Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence. RESULTS: Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group. CONCLUSIONS: CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients who switched to CT-P13 after 54 weeks of IFX treatment. The study also demonstrated a stable clinical efficacy of CT-P13 in RA patients.
28552437 Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthr 2019 Jan OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. METHODS: Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. RESULTS: 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. CONCLUSIONS: In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population.
28087832 Comparison of cardiovascular risk algorithms in patients with vs without rheumatoid arthri 2017 May 1 OBJECTIVES: The aims were to compare the performance of cardiovascular risk calculators, Framingham Risk Score (FRS) and QRISK2, in RA and matched non-RA patients and to evaluate whether their performance could be enhanced by the addition of CRP. METHODS: We conducted a retrospective analysis, using a clinical practice data set linked to Hospital Episode Statistics (HES) data from the UK. Patients presenting with at least one RA diagnosis code and no prior cardiovascular events were matched to non-RA patients using disease risk scores. The overall performance of the FRS and QRISK2 was compared between cohorts, and assessed with and without CRP in the RA cohort using C-Index, Akaike Information Criterion (AIC) and the net reclassification index (NRI). RESULTS: Four thousand seven hundred and eighty RA patients met the inclusion criteria and were followed for a mean of 3.8 years. The C-Index for the FRS in the non-RA and RA cohort was 0.783 and 0.754 (P < 0.001) and that of the QRISK2 was 0.770 and 0.744 (P < 0.001), respectively. Log[CRP] was positively associated with cardiovascular events, but improvements in the FRS and QRISK2 C-Indices as a result of inclusion of CRP were small, from 0.764 to 0.767 (P = 0.026) for FRS and from 0.764 to 0.765 (P = 0.250) for QRISK2. The NRI was 3.2% (95% CI: -2.8, 5.7%) for FRS and -2.0% (95% CI: -5.8, 4.5%) for QRISK2. CONCLUSION: The C-Index for the FRS and QRISK2 was significantly better in the non-RA compared with RA patients. The addition of CRP in both equations was not associated with a significant improvement in reclassification based on NRI.
27470086 Use of a risk characterisation approach to contextualise the safety profile of new rheumat 2017 Mar Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To characterise the relative safety profile of tofacitinib to biologic disease-modifying antirheumatic drugs (bDMARDs), the accrued patient-years (pt-yrs) of exposure needed in an RA clinical trial programme to detect a potential increase in risk of specific adverse events (AEs) was determined. This case study/framework was constructed on the pt-yrs' accrual within pooled phase (P)1, P2 and P3, as well as long-term extension, studies of tofacitinib in RA (March 2015 data-cut) and published AE incidence rates for bDMARDs. Sample size calculations were based on a Poisson distribution to estimate pt-yrs' exposure required for 90 % probability that the lower bound of the 95 % confidence interval for tofacitinib/bDMARD would be >1, assuming that tofacitinib rates were 1.2×/1.5×/2.0× greater than comparator rates. AE rates for bDMARDs were derived from sources intended to optimise similarity with the tofacitinib database in terms of baseline characteristics, study duration and follow-up. Based on the tofacitinib exposure accrued (19,406 pt-yrs), data were sufficient (90 % probability) to detect potential differences over external bDMARD comparator rates in serious infections (≥1.2×), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, major adverse cardiovascular events (MACE) and lymphoma (each ≥1.5×), as well as opportunistic infections and gastrointestinal perforations (≥2×), should they exist. This risk characterisation approach can support the comparative safety of new RA medications. To date, tofacitinib safety appears similar to approved published data from bDMARDs with respect to serious infections, malignancies (excluding NMSC), NMSC, MACE, lymphoma, opportunistic infections and gastrointestinal perforations.
28426141 Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8(+) T Cytotoxic 2017 Jul Melanocortin signalling in leucocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signalling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptors (MC1-5R) gene expressions in pathogenetic leucocyte subsets in rheumatoid arthritis (RA) to treatment with TNF-α inhibitor adalimumab. Seven patients with active RA donated blood at start and at 3-month treatment. CD4(+) T helper (h) lymphocytes (ly), CD8(+) T cytotoxic (c) ly, CD19(+) B ly and CD14(+) monocytes were isolated, using immunomagnetic beads, total RNA extracted and reverse transcription quantitative polymerase chain reaction (RT-qPCR) performed. Fold changes in MC1-5R, Th1-, inflammatory- and regulatory cytokine gene expressions were assessed for correlation. Six patients responded to adalimumab treatment, while one patient was non-responder. In all lymphocyte subtypes, MC1-5R gene expressions decreased in responders and increased in the non-responder. In responders, decrease in MC2R, MC3R and MC4R gene expressions in CD8(+) Tc and CD19(+) B ly was significant. Fold change in MC1-5R and IFNγ gene expressions correlated significantly in CD8(+) Tc ly, while fold change in MC1R, MC3R and MC5R and IL-1β gene expressions correlated significantly in CD4(+) Th ly. Our results show regulation of MC2R, MC3R and MC4R gene expressions in CD8(+) Tc ly and CD19(+) B ly. The correlations between fold change in different MCRs and disease driving cytokine gene expressions in CD8(+) Tc ly and CD4(+) Th ly point at a central immune modulating function of the melanocortin system in RA.
28598781 Health care utilisation before and after intensive care unit admission in rheumatoid arthr 2017 Nov OBJECTIVES: We evaluated the incidence of intensive care unit (ICU) admission in a rheumatoid arthritis (RA) population according to health care utilisation and use of immune therapies in the year preceding admission. Also, we compared health care utilisation after ICU admission in persons with and without RA. METHODS: We identified all persons with RA in Manitoba, Canada using population-based administrative data, and controls matched by age, sex, and region of residence. ICU admissions were identified using special care unit codes included in hospital discharge abstracts. We estimated the annual incidence rate of ICU admission in the RA population according to health care utilisation using generalised linear models, adjusting for age, sex, comorbidity, region and socioeconomic status. We compared health care utilisation post-ICU admission in persons with and without RA. RESULTS: From 2000/01 through 2009/10, the average annual incidence of ICU admission was 1.26% in the RA population. Corticosteroid use was associated with an increased incidence of ICU admission (IRR 1.07; 95%CI: 1.05, 1.09). Use of disease-modifying anti-rheumatic drugs and biologics was not associated with an increased incidence of ICU admission. In the year following ICU admission, 45.3% of the RA population was re-hospitalised, and 8.9% were readmitted to the ICU. CONCLUSIONS: Persons with RA who are admitted to the ICU have higher rates of health care utilisation in the year before ICU admission than those who are not admitted. Corticosteroid use is associated with an increased risk of ICU admission even after accounting for other health care utilisation.
28510734 Predictors of and outcomes following orthopaedic joint surgery in patients with early rheu 2017 Sep 1 OBJECTIVES: To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. METHODS: Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. RESULTS: Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]. CONCLUSION: HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.
28053250 The painful total ankle arthroplasty: a diagnostic and treatment algorithm. 2017 Jan The last decade has seen a considerable increase in the use of in total ankle arthroplasty (TAA) to treat patients with end-stage arthritis of the knee. However, the longevity of the implants is still far from that of total knee and hip arthroplasties. The aim of this review is to outline a diagnostic and treatment algorithm for the painful TAA to be used when considering revision surgery. Cite this article: Bone Joint J 2017;99-B:5-11.
28866634 Quality of reporting of harms in randomised controlled trials of pharmacological intervent 2017 Oct BACKGROUND: The quality of reporting of harms data in randomised controlled trials (RCTs) has been reported to be suboptimal. Rheumatoid arthritis (RA) has seen a massive growth in novel pharmacotherapies in the last decade. OBJECTIVE: The aim of this study was to assess the quality of reporting of harms-related data in RCTs evaluating pharmacological interventions for RA according to the CONSORT (Consolidated Standards of Reporting Trials) statement on harms reporting extension. STUDY SELECTION: RCTs published between January 2011 and August 2016 in the five highest impact factor journals in general medicine and two in rheumatology subject categories as per 2015 Journal Citation Reports were included. Reports of secondary, supplementary or exploratory analyses of RCTs and non-inferiority trials were excluded. Two reviewers independently extracted data using a structured, pilot-tested, 18-item questionnaire developed based on CONSORT harms extension recommendations. FINDINGS: 68 RCTs were included in the review. Out of a maximum harms reporting score of 18, the mean (SD) score was 8.51 (3.5) (range=0-15). More than half (56.5%) of the RCTs reported ≤50% of items and only three (4.3%) RCTs reported more than 70% (score ≥14) of the items. Multilinear regression analyses found that region of trial origin (p=0.01), sample size (p=0.001) and whether the study was a long-term extension of a trial or not (p=0.04) were independent predictors associated with higher total harms reporting score. CONCLUSIONS: The adherence to CONSORT harms extension was poor in recently published RCTs of pharmacological interventions for RA. There is a need to improve quality of harms reporting in RCTs to allow transparent and balanced assessment of the benefit-risk ratio in clinical decision making.
28134079 Development and validation of rheumatoid arthritis magnetic resonance imaging inflammation 2017 Jul OBJECTIVES: To determine thresholds for rheumatoid arthritis (RA) magnetic resonance imaging scores (RAMRIS) associated with a low risk of structural damage progression. METHODS: MRI of the dominant hand was performed and RAMRIS scores determined at weeks 0, 24, and 52. X-rays were performed and van der Heijde-Sharp scores (vdHS) determined. In a development cohort (n=297) the changes in MRI erosion score and vdHS score were determined over the 24-week to 52-week interval and progression was defined as change >0.5. We identified 24-week thresholds for synovitis and osteitis that provided >90% sensitivity for imaging progression over the 24 to 52-week interval. The performance of these cut-offs was tested in a validation cohort (n=217). RESULTS: In the development cohort, synovitis or osteitis scores ≤3 by 24 weeks were associated with a low probability of progression on MRI and x-ray. The coefficient for osteitis was stronger than that of synovitis in models predicting x-ray and MRI progression. Therefore, a total inflammation score was weighted on osteitis (x2). An inflammation score ≤9 was more frequently attained than DAS28 remission (64 vs. 38) and was associated with low probability of progression regardless of attainment of clinical remission. In the validation cohort, there was a low odds of MRI progression among those with low synovitis [OR 0.27 (0.086,0.82) p=0.02], osteitis [OR 0.20 (0.085, 0.49) p<0.001] and inflammation scores [OR 0.12 (0.033, 0.41) p=0.001]. CONCLUSIONS: Attainment of low MRI single-hand synovitis and osteitis is not uncommon and predicts a lack of structural progression in RA, independent of clinical remission.
28858091 Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoi 2017 Sep BACKGROUND: Several studies investigated the relationship between programmed cell death 1 (PDCD1) gene polymorphisms and rheumatoid arthritis (RA) risk, but the results were controversial. To explore whether PDCD1 gene polymorphisms have an effect on RA risk, we conducted this meta-analysis to investigate the relationships between PDCD1 polymorphisms (rs36084323 [PD-1.1 G/A], rs11568821 [PD-1.3 G/A] and rs2227981 [PD-1.5 C/T]) and RA risk under 4 genetic models. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBLM) were systematically searched for all eligible case-control studies. The last search was updated on September 10, 2016. Studies were accessed using Newcastle-Ottawa Scale case control study (NOS), and the combined effect size was calculated using STATA software, version 12.0. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association. Heterogeneity analysis and subgroup analysis were also performed. Sensitivity analysis and publication bias were also performed if necessary. RESULTS: This meta-analysis included 6 studies. The result demonstrated null association between rs36084323 (PD-1.1 G/A) polymorphism and RA susceptibility in all 4 genetic models. With regard to rs11568821 (PD-1.3 G/A), statistically significant association with RA risk was observed under allele model in Caucasians (allele model A vs G, OR = 1.19, 95% CI = 1.03-1.41). There was no significant association between rs2227981 (PD-1.5 C/T) polymorphism and RA risk. CONCLUSION: The present study suggests that mutant A allele in rs11568821 (PD-1.3 G/A) might increase the susceptibility to RA in Caucasians.
29246532 An e-health interactive self-assessment website (Sanoia(®)) in rheumatoid arthritis. A 12 2018 Dec INTRODUCTION: Sanoia is an online interactive electronic e-health platform developed to allow patient self-assessment and self-monitoring. The objective was to assess in rheumatoid arthritis (RA) patients, the efficacy on patient-physician interactions, of giving access to Sanoia. METHODS: In this French, multi-center, 12-months randomized controlled trial (CarNET: NCT02200068), patients with RA and internet access were randomized to: access without incentives to the Sanoia platform after minimal training, or usual care. The primary outcome was the change from baseline in patient-physician interactions, by the patient-reported Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) questionnaire. The number of accesses to Sanoia was recorded and satisfaction with the platform was assessed through a 0-10 numeric rating scale. Analyses were in intention to treat (ITT), on SAS. RESULTS: Of 320 RA patients (159 Sanoia versus 161 usual care), mean (standard deviation) age was 57.0 (12.7) years, mean (SD) disease duration was 14.6 (11.1) years, 216 (67.5%) were taking a biologic and 253 (79.1%) were female. Mean (SD) PEPPI scores at baseline and 12 months were 38.6 (8.2) and 39.2 (8.0) (delta=+0.60 [5.52]) versus 39.7 (7.3) and 38.8 (8.0) (delta=-0.91 [6.08]) in the Sanoia and control group, respectively (P=0.01). Although mean satisfaction with the platform was very high (1.46 [1.52]), 41 patients (25.7%) never accessed Sanoia. CONCLUSION: Giving RA patients access to the interactive Sanoia e-health platform led to a small improvement in patient-perceived patient-physician interactions. A disjunction between patient satisfaction and access to the platform was noted. E-Health platforms are promising in RA.
28550389 Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from 2017 Jul Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.
29477035 Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis 2018 Apr BACKGROUND: Previously, we have demonstrated that kynurenic acid (KYNA), an endogenous metabolite of tryptophan formed along kynurenine pathway, is present in synovial fluid of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In this study, the goal was to investigate the presence of quinaldic acid (QUDA), a putative metabolite of KYNA, in synovial fluid of RA and OA patients. METHODS: The effect of QUDA on proliferation and motility of synovial fibroblasts and its interaction with KYNA were determined in vitro. The study was conducted on synovial fluid obtained from 38 patients with RA and 15 patients with OA. QUDA was identified and quantified using the gas chromatography-mass spectrometry (GC-MS) method. In vitro experiments were conducted on rabbit synoviocyte cell line HIG-82. RESULTS: Presence of QUDA was detected in all 53 samples of synovial fluid. The concentration of QUDA in synovial fluid obtained from patients with RA was 28.6 ± 14.9 pmol/ml, which was lower in comparison with OA 42.3 ± 10.0 pmol/ml. QUDA content positively correlated with the number of tender joints and negatively with the total cell counts determined in synovial fluid of RA patients. It did not correlate with KYNA content. QUDA reduced both proliferation and motility of synoviocytes in a dose-dependent manner. The enhancement of antiproliferative action of QUDA by KYNA was evidenced. CONCLUSIONS: Data show a local deficit of QUDA in RA patients and suggest its potential role as an endogenous substance controlling synoviocyte viability.
27925155 Enhanced liver fibrosis test in patients with psoriasis, psoriatic arthritis and rheumatoi 2017 Jun BACKGROUND: The enhanced liver fibrosis (ELF) test has been introduced to screen, diagnose and/or monitor liver conditions in large groups of patients with liver diseases. It has not been used in inflammatory skin or joint diseases. OBJECTIVES: To evaluate the distribution of the ELF test, apply existing cut-offs for hepatic patients and healthy controls, and compare it with the procollagen-3 N-terminal peptide (P3NP) test in patients with psoriasis (PSO), psoriatic arthritis (PsA) and rheumatoid arthritis (RA), and controls. METHODS: In total, 531 patients were included. Demographic, lifestyle and disease-specific data were collected. ELF and P3NP tests were performed. RESULTS: Prevalence of an increased ELF score (> 11) and P3NP was highest in patients with RA (7·7% and 6·1%, respectively) followed by patients with PSO (1·7% and 5·2%, respectively) and PsA (0·7% and 1·3%, respectively). Mean ± SD ELF scores for PSO, PsA and RA were, respectively, 9·09 ± 0·86, 8·96 ± 0·76 and 9·55 ± 1·04. All subgroups with moderate-to-severe disease severity had higher (> 9·8) ELF scores (PSO 27·0% vs. 18·3%; PsA 19·2% vs. 12%; RA 45·8% vs. 30·5%) and P3NP values. Distribution of the ELF score was smaller than the P3NP value [mean ± SD: 9·15 ± 0·92 (range 6·53-13·05) vs. 8·37 ± 4·30 (range 0·53-63·88)]. CONCLUSIONS: ELF score and P3NP are elevated in PSO, PsA and RA. ELF may be superior to P3NP alone, but further research should be done to validate the ELF test in determining susceptibility for developing liver fibrosis in PSO, PsA and RA.
27859022 Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shar 2017 Apr Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses is important. In the present study, we analysed the immunoglobulin (Ig)G subclasses regarding reactivity against cyclic citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status and IgA and pan-IgG anti-CCP antibodies. All patients, regardless of pan-IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity. Sixty-nine per cent were positive in any IgG anti-CCP subclass, and of these 67% tested positive regarding IgG1, 35% IgG2, 32% IgG3, and 59% IgG4 anti-CCP. Among ever-smokers the percentages of IgG2 anti-CCP (P = 0·01) and IgA anti-CCP (P = 0·002)-positive cases were significantly higher compared to never-smokers. A positive IgG anti-CCP subclass -negative cases. Combining SE and smoking data revealed that IgG1 and IgG4 anti-CCP were the IgG anti-CCP isotypes associated with expression of SE, although the lower number of patients positive for IgG2 or IgG3 anti-CCP could, however, have influenced the results. High levels of IgG2 anti-CCP were shown to correlate with expression of the 'non-SE' allele human leucocyte antigen (HLA)-DRB1*15. In conclusion, in this study we describe different risk factor characteristics across the IgG anti-CCP subclasses, where IgG2 appears similar to IgA anti-CCP regarding the predominant association with smoking, while IgG1 and IgG4 related more distinctly to the carriage of SE genes.
28681148 Effects of denosumab treatment on bone mineral density and joint destruction in patients w 2018 Jul We aimed to investigate the efficacy of denosumab for rheumatoid arthritis (RA). This study enrolled 70 RA patients who received denosumab 60 mg subcutaneous injection at baseline and at 6 months. Bone mineral densities (BMD) of the lumbar spine, total hip, femoral neck, and hand were measured by dual energy X-ray absorptiometry. Changes in total modified Sharp score (mTSS), erosion (EN) score, and joint space narrowing score at baseline from 12 months before and at 12 months from baseline. The mean values of BMD of the lumbar spine, total hip, femoral neck, and hand significantly increased by 7.3, 4.7, 3.9, and 5.4%, respectively, at 12 months. At 12 months from baseline, there were significant decreases in the values of mTSS (1.13 vs. 0.59; p = 0.002) and EN score (0.40 vs. 0.07; p < 0.001), compared with the values at baseline from 12 months before. The existing combined modality therapy with denosumab might be effective for osteoporosis and joint destruction in patients with RA.
28256939 Increased Levels of STAT1 Protein in Blood CD4 T Cells from Systemic Lupus Erythematosus P 2017 Jun In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4(+)FOXP3(+) regulatory T cells (Tregs) were described. In the present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity. The highest STAT1 MFI was found in CD45RA(-)FOXP3(hi)-activated Treg (aTreg) subset, which demonstrated the highest STAT1 phosphorylation responses among SLE CD4 T cells and significant decrease in proliferation marker Ki-67 expression after IFN-alpha stimulation. Percentage of Ki-67(+) aTregs was significantly decreased in SLE patients and was negatively correlated with CD4 T cell STAT1 MFI. A subgroup of SLE patients characterized by lower aTreg counts experienced more severe relapsing disease course during 1,000 days of follow-up. Mean CD4 T cell STAT1 MFI in follow-up samples from SLE patients was negatively correlated with mean of follow-up aTreg counts. Our findings indicate that augmented STAT1 signaling may be involved in perturbed aTreg homeostasis, which could represent a possible marker of SLE disease severity.