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ID PMID Title PublicationDate abstract
27706751 Association between peptidyl arginine deiminase 4 (PADI4)-104C/T polymorphism and rheumato 2016 Sep 19 The correlation between the -104C/T polymorphism in the peptidyl arginine deiminase 4 (PADI4) gene and rheumatoid arthritis (RA) risk has been analyzed in several studies. However, the results are inconclusive and remain to be confirmed in several ethnic groups. The effect of the PADI4-104C/T polymorphism on RA risk in the Chinese population was evaluated in a meta-analysis. Studies with dates of publication up to July 2015 conforming to the inclusion criteria were retrieved from PubMed and Chinese databases. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Ten studies, including 2119 RA cases and 1962 controls, that conformed to the study criteria were included in this analysis. The overall analysis indicated a significant association between the PADI4-104C/T polymorphism and RA risk in the Chinese population (T vs C: OR = 1.45, 95%CI = 1.18-1.78; TT vs CC: OR = 1.49, 95%CI = 1.24-1.80; TT vs CC+CT: OR = 1.28, 95%CI = 1.08-1.51; TT+CT vs CC: OR = 1.75, 95%CI = 1.30-2.37). Analysis of data stratified by the geographic area and source of controls revealed that the PADI4-104C/T polymorphism was significantly associated with RA risk in a North Chinese population. In conclusion, the results of this meta-analysis indicated that the PADI4-104C/T variants could influence the risk of RA in the Chinese population; further studies in other ethnic groups are required to draw definite conclusions.
26941186 Serum cathepsin S and cystatin C: relationship to subclinical carotid atherosclerosis in r 2016 Mar OBJECTIVES: To assess whether serum cathepsin S and cystatin C, two novel markers of cardiovascular disease risk, are associated with subclinical carotid atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Serum cystatin C and cathepsin S levels, carotid intima-media thickness (cIMT) and carotid plaques were assessed in a cross-sectional study involving 178 RA patients. RESULTS: An association between disease activity scores with higher levels of cystatin C, but not with cathepsin S, was found. Cystatin C levels were also associated with cIMT in the patient subgroup included in the higher quartile of Cimt (OR 1.31, 95%CI [1.00-1.72], p=0.04) after adjusting for traditional cardiovascular risk factors, age and sex. An association between serum cystatin C levels and carotid plaques was also found in the univariate analysis (OR 1.37, 95%CI [1.06-1.76], p=0.02). However, this significant association was lost after adjusting for traditional cardiovascular risk factors and age. Cathepsin S was not associated with cIMT or carotid plaques. CONCLUSIONS: High cystatin C serum levels identify a subgroup of RA patients with a high risk of subclinical atherosclerotic disease.
26962036 Total glucosides of paeony for rheumatoid arthritis: a protocol for a systematic review. 2016 Mar 9 INTRODUCTION: Total glucosides of paeony (TGP) is a natural plant extract, which is widely used in China for treating rheumatoid arthritis (RA). Many relevant randomised controlled trials (RCTs) of TGP for RA are available, but they have not been systematically reviewed. This systematic review aims to examine the effectiveness and safety of TGP in patients with RA. METHODS AND ANALYSES: We will search for RCTs of TGP in the treatment of RA, performed up until February 2016, in PubMed, Embase, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database). Trial registers and reference lists of retrieved articles will also be searched to identify potential articles. RCTs comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs for patients with RA will be retrieved. The primary outcomes will be disease improvement and disease remission. The secondary outcomes will be surrogate outcomes, symptoms, adverse effects, and quality of life. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes, etc. The methodological quality of each included study will be evaluated using the Cochrane risk of bias tool, and the strength of evidence on prespecified outcomes will be assessed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Review Manager 5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous, both statistically and clinically. Possible publication bias will also be checked using funnel plots once the number of included studies is sufficient. ETHICS AND DISSEMINATION: Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research. TRIAL REGISTRATION NUMBER: CRD42015026345.
26483255 Prediction of disease relapses by multibiomarker disease activity and autoantibody status 2016 Sep OBJECTIVE: To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. METHODS: MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. RESULTS: Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). CONCLUSIONS: MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. TRIAL REGISTRATION NUMBER: EudraCT 2009-015740-42.
27214767 Comparing a tapering strategy to the standard dosing regimen of TNF inhibitors in rheumato 2016 Jul OBJECTIVES: The aim of this study is to compare clinical outcomes, incidence of flares and administered drug reduction between rheumatoid arthritis (RA) patients under TNF inhibitors (TNFi) tapering strategy and RA patients on standard regimen. METHODS: Two groups of RA patients on TNFi with DAS28<3.2 were compared: the tapering group (TG: 67 pts from Spain) and the control group with standard therapy regimen (CG: 77 pts from the Netherlands). DAS28 was measured at different time points: visit 0 (prior starting TNFi), visit 1 (prior to start tapering in TG and with DAS28<3.2 in TG and CG), visit 2 (6 months after visit 1), visit 3 (1 year after visit 1), visit 4 (the last visit available after visit 1) and visit-flare (visit with the worst flare between visit 1 and visit 4). RESULTS: Despite the reduction of administered drug at visit 4 in the TG (interval elongation of 32.8% in infliximab, 52.9% in adalimumab and 52.6% in etanercept), the DAS28 remained similar between groups at the end of the study (DAS28: 2.7±0.9 in TG vs. 2.5±1 in CG, p=0.1). No differences were seen in the number of patients with flares [26/67 (38.9%) in the TG vs. 30/77 (39%) in the CG, p=0.324] and only nineteen out of 136 patients (14%) had anti-drug antibodies at the end of the study. CONCLUSIONS: The tapering strategy of TNFi in RA patients result in a reduction of the drug administered, while the disease control is not worse than patients on the standard regimen.
25924443 [Immune mediated inflammatory pathogenesis and assessment of disease activity in rheumatoi 2015 Mar Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease with synovitis and pannus formation as its basic pathologic features. Immune mediated inflammation is the core event in the occurrence and development of RA, but the inflammatory mechanism in RA pathogenesis remains unclear and needs more research to be illustrated. T cells, B cells, proinflammatory cytokine network and chemokines were confirmed to be involved in the process. In addition, the cells related to the structure of bone and joint, such as synovial cells, osteoblasts and osteoclasts, also participate in the inflammation progression of RA acting as the effector cells of immune regulation. The severity of inflammation of RA is closely related to disease activity. There are many kinds of tools for the assessment of disease activity of RA, The rationale use and optimization of these assessment tools will be helpful to make the treatment decision and improve the prognosis of RA.
25520183 Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options. 2015 Mar OBJECTIVE: Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. Citrullinations are the conversion of arginine to citrulline by peptidylarginine deiminase (PAD) enzymes, which affect protein properties. The aim of this review is to summarize the advances in citrullination research and further explore the potential of citrullination as a diagnostic tool as well as inhibition of PAD enzymes as a target for treatment. METHOD: We reviewed current literature with emphasis on the role of citrullination in health and disease, the nature of enzymes responsible for citrullination, and the potential of applying citrullinations in diagnostics and pharmaceuticals. CONCLUSION: Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. In RA measurement of anti-citrullinated protein antibodies (ACPA) against citrullinated protein fragments are widely used as a prognostic biomarker. More recently, it has been indicated that levels of selected citrullinated proteins carries additional potential as biomarkers. This includes citrullinated vimentin which provide prognostic information in diseases as fibrosis and ankylosing spondylitis. In addition, recent studies suggest that inhibition of PAD is a target for treatment of diseases such as RA and cancer where proteins that are citrullinated are believed to influence the disease activity.
27796445 Biologic therapies and bone loss in rheumatoid arthritis. 2017 Feb INTRODUCTION: Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. METHODS: Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents." CONCLUSION: Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
27864689 Epstein-Barr virus infection and gene promoter hypermethylation in rheumatoid arthritis pa 2017 Feb We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)(+) DLBCL. Among them, tumor cells from EBV(+) MTX-BLPD patients and control EBV(+) DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2.3 and 1.7 vs. 4.3 and 4.4; P < 0.01 for each). In the MTX-BLPD group, EBV(+) patients showed lower median CIMP than EBV(-) patients (2.3 vs. 3.2); they also had significantly lower hypermethylation incidence in four apoptosis-related genes, especially death-associated protein kinase (14 vs. 55 %), higher incidence of massive tumor necrosis (86 vs. 27 %), and lower BCL2 protein expression (19 vs. 86 %) than did the control DLBCL group (P < 0.01 for all). In all clinical stages, EBV(+) MTX-BLPD patients had better prognoses than the EBV(-) MTX-BLPD (P = 0.011), non-MTX-BLPD (P = 0.002), and control DLBCL groups (P = 0.015). MTX-BLPD patients without hypermethylated RAS-associated domain family-1A (RASSF1A) or O (6) -methyl guanine-DNA methyltransferase (MGMT) had significantly better prognosis than those with hypermethylation of those genes (P = 0.033). We conclude that in RA patients with MTX-BLPD, EBV infection is associated with a lower incidence of CIMP, apoptosis-related gene hypermethylation, and BCL2 expression, which can induce tumor regression by MTX withdrawal and lead to better prognoses.
25736038 Tespa1 is associated with susceptibility but not severity of rheumatoid arthritis in the Z 2015 Apr Observational and experimental studies in animal models have shown that Tespa1 may be associated with B cell function and the onset of rheumatoid arthritis (RA). We hypothesized that Tespa1 may also play an important role in patients with RA. To test this hypothesis, we investigated the expression level, gene polymorphisms, and promoter methylation of the Tespa1 gene in 77 RA patients and 113 matched healthy controls. We found that the expression of Tespa1 is significantly lower in RA patients with both low and moderate-to-high disease activity. Moreover, patients with familial (first-degree siblings) but not sporadic RA have a statistically significant difference at the rs4758993 locus with healthy people. Furthermore, we found seven methylation sites on the Tespa1 promoter, but no evidence of the association between methylation at these sites and RA susceptibility. These data support a potential role for Tespa1 in the pathogenesis of RA.
27852695 Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthr 2017 May OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of common anti-inflammatory treatments on HDL function are not yet known. METHODS: We compared the function of HDL in 18 patients with RA and 18 matched healthy controls. Subsequently, patients were randomised to (methotrexate+infliximab (M+I) (5 mg/kg)) or methotrexate+placebo (M+P) infusions for 54 weeks. At week 54 and thereafter, all patients received infliximab therapy until completion of the trial (110 weeks), enabling assessment of the impact of 1 year of infliximab therapy in all patients. HDL functional properties were assessed at baseline, 54 weeks and 110 weeks by measuring the impact on endothelial nitric oxide (NO) bioavailability and superoxide production (SO), paraoxonase activity (PON-1) and cholesterol efflux. RESULTS: All HDL vascular assays were impaired in patients compared with controls. After 54 weeks, NO in response to HDL was significantly greater in patients who received M+I compared with those who received M+P. Endothelial SO in response to HDL was reduced in both groups, but PON-1 and cholesterol efflux remained unchanged. All vascular measures improved compared with baseline after ≥1 infliximab therapy in the analysis at 110 weeks. No significant trend was noted for cholesterol efflux. CONCLUSIONS: HDL function can be improved with anti-inflammatory treatment in patients with RA. The M+I combination was superior to the M+P alone, suggesting that the tumour necrosis factor-α pathway may have a role in HDL vascular properties.
25502945 Genetics of neuroendocrine factors in rheumatoid arthritis. 2015 Jun Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed.
26875801 Shoulder replacements: a review. 2016 Feb Shoulder replacement surgery is a common elective surgical procedure for those with progressive osteoarthritis and rheumatoid arthritis. This review explores the history of shoulder replacements, the different types of replacements and their advantages or disadvantages.
27797345 FDG PET Imaging of Extremities in Rheumatoid Arthritis. 2016 Sep BACKGROUND: The primary objective of this study was to evaluate the utility of fluorodeoxyglucose positive emission tomography imaging in assessing the degree of joint inflammation and response to therapy in patients with rheumatoid arthritis using standard PET parameters. METHODS: Five subjects with newly diagnosed RA were enrolled in this IRB-approved prospective study. After standard conventional workup that included clinical and laboratory evaluation and disease activity score (DAS3v) calculation, subjects underwent baseline FDG PET scans of their hands and feet prior to initiation of treatment and after six months of standard treatment. The uptake of FDG in involved joints was assessed qualitatively (visual evaluation) as well as semi quantitatively using standardized uptake value (SUV). Findings from the FDG PET scans were correlated with clinical and laboratory parameters including DAS and ESR. RESULTS: In all five patients, increased FDG uptake was noted in various joints affected by RA. The intensity of uptake varied from mild to intense (SUVmax values from 3.10 to 6.0). Overall, these correlated well with the clinical evaluation of involved joints. FDG PET imaging provided additional information by showing involvement in joints that were difficult to evaluate clinically (e.g. mid foot joints). The PET data also provided a distribution of joint involvement with varying degrees of severity in the same subject. On objective analysis using Spearman rank correlation coefficient for statistical analysis, no significant correlations were observed (p>0.05) between DAS, ESR, and the different PET parameters at baseline (before treatment) despite large calculated positive correlation coefficients. This was due to the small sample size (n=5). At post-treatment, the significant correlations were those between DAS and Maximum metabolic disease burden (MDB max) (RS=0.9, p=0.04) and between ESR and MDB max (RS=0.9, p=0.04). The positive correlations between total metabolic disease burden (Total MDB) and DAS (RS=0.7) and between Total MDB and ESR were also large (RS=0.7) but not significant. The non-significance was due to the small sample size. CONCLUSIONS: FDG PET imaging provides a unique noninvasive quantitative method in assessing disease status and response to therapy and can serve as a useful adjunct to clinical evaluation in management of patients with rheumatoid arthritis.
27258623 Should tumour necrosis factor antagonist safety information be applied from patients with 2017 Mar BACKGROUND: Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. OBJECTIVES: To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. METHODS: We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). RESULTS: There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. CONCLUSIONS: Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases.
26237970 [Influence of Moxibustion on TLR 4-MyD 88-NF-KB Signal Transduction Pathway of Synovial Ti 2015 Jun OBJECTIVE: To observe the effect of moxibustion intervention on the expression of toll-like receptor-4 (TLR 4), myeloid differentiation factor 88(MyD 88), and nuclear factor kappa B p 65 (NF-κB p 65) genes of knee-joint synovial cells in rheumatoid arthritis (RA) rats, so as to explore its molecular mechanism underlying improving RA. METHODS: Forty SD rats were randomly divided into normal control, RA model, moxibustion and medication groups (n = 10). The RA model was duplicated by raising the rats in a windy, cold and wet environment, followed by injecting Freund's complete adjuvant (0. 15 mL) into the rat's foot. Moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 min, once daily for 15 days. Rats of the medication group were treated by intragastric administration of tripterygium wilfordii (8. 75 mL/kg), once daily for 15 days. Pathological changes of the synovial tissues were detected by H. E. stain, the contents of serum TNF-α and IL-1 detected by radioimmunoassay, and the expression levels of TLR 4 mRNA, MyD 88 mRNA and TRAF-6 mRNA of synovial tissue were analyzed by real time-PCR, and the NF-κB p 65 immunoactivity was assayed by immunohistochemistry. RESULTS: In comparison with the normal control group, the synovial tissue of the knee-joint was impaired remarkably and infiltrated by numerous inflammatory cells, and the synovial surface got thickening because of hyperplasia in the model group. Following moxibustion and medication, these situations such as synovial infiltration of inflammatory, synovial cell proliferation were alleviated. The serum TNF-α and IL-1 contents and synovial TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 expression levels were remarkably higher in the model group than in the control group(P<0. 01). After moxibustion and medication, the contents of serum TNF-α and IL-1, the expression levels of TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 were significantly down-regulated(P<0. 01, P<0. 05). CONCLUSION: Moxibustion intervention can improve pathological changes of the knee-joint synovial membrane tissue in RA rats, which may be related with its effect in inhibiting abnormal activation of TLR 4-MyD 88-NF-κB pathway in synovial tissue.
27856656 Stopping tumour necrosis factor-targeted biological DMARDs in rheumatoid arthritis. 2016 Dec The combined use of MTX and biological DMARDs (bDMARDs) targeting TNF has revolutionized treatment of RA, and clinical remission becomes a realistic treatment goal. After sustained remission, discontinuation of bDMARDs without disease flare has been emerging as an important theme from the risk-benefit point of view and economic burden. According to several studies, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining low disease activity or remission by treatment with bDMARDs and MTX. For established RA, however, fewer patients sustained remission or low disease activity after the discontinuation of bDMARDs, compared with early RA. The results were controversial among studies, and the percentage of patients who could successfully discontinue bDMARDs ranged from 13 to 48% at 1 year after discontinuation. From the adalimumab discontinuation without functional and radiographic damage progression following sustained remission study and the induction of remission by infliximab in RA study, deep remission at discontinuation was a key factor for maintaining the treatment holiday of bDMARDs in established RA patients. However, such early intensive treatment would have the potential for reducing drug-induced adverse effects and reducing long-term medical costs, although the risks of worsening clinical, structural and functional outcomes should be considered, with careful monitoring.
26342228 Recent insights into the role of autophagy in the pathogenesis of rheumatoid arthritis. 2016 Mar Autophagy appears to play a dual role in eukaryotic cells. It manifests cytoprotective effects through the regulation of catabolic processes and the clearance of pathogens; however, a correlation between autophagy and the pathogenesis of autoimmune/autoinflammatory conditions has recently been described. Autophagy has emerged as a mediator in the pathogenesis of RA. Autophagy may regulate apoptosis resistance and hyperplasia in synovial fibroblasts, promote osteoclastogenesis and stimulate osteoclast-mediated bone resorption through the delivery of citrullinated peptides to MHC compartments, which results in the activation of the innate and adaptive immune response, thereby resulting in RA. Given the likely importance of autophagy in the pathogenesis of RA, here we reviewed the detailed mechanisms concerning the pathogenicity of autophagy and autophagy proteins in RA.
26846791 Seasonal variations in fatigue in persons with rheumatoid arthritis: a longitudinal study. 2016 Feb 4 BACKGROUND: Fatigue is a prominent symptom in persons with rheumatoid arthritis (RA). Although this symptom has been described to vary in duration and frequency little is known about fluctuations in fatigue over time and season. The aim of this study was to describe monthly and seasonal variations in fatigue, in persons with RA of working age. METHODS: Sixty-five participants diagnosed with RA and aged 20-65 years were recruited from a rheumatology clinic in Sweden. The participants provided self-assessments of their fatigue at seven time points during the four seasons using a 0-100 mm visual analogue scale (VAS) and the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Multiple regression analysis using mixed models was used to analyze changes in fatigue over time. RESULTS: The mean ± SD of fatigue rated on the VAS was 51 ± 13, indicating substantial fatigue. Analysis of monthly variation showed statistically significant variation in fatigue ratings concerning VAS fatigue score (p < 0.01) as well as the BRAF-MDQ total score and Living, Cognition (p < 0.001), and Physical (p < 0.05) sub-scores, but not the BRAF-MDQ Emotional sub-score. The greatest variations were seen from January to September, with higher fatigue ratings in January. The changes in VAS fatigue scores over time were considered to be of clinical importance. Analysis of seasonal variation revealed a statistically significant seasonal variation in fatigue levels, with higher fatigue values during the winter as measured by VAS fatigue score (p < 0.01) as well as BRAF-MDQ total score (p < 0.01) and Physical and Living sub-scores (both p < 0.01). The greatest variation was seen between winter and autumn for VAS fatigue and between winter and summer for BRAF-MDQ total score and Physical and Living sub-scores. There were no statistical differences in fatigue levels, monthly or seasonal, between sexes or age groups. CONCLUSIONS: The majority of rating scales used in this study showed fluctuations in fatigue, general and physical fatigue being significantly greater during the winter. As fatigue is a substantial symptom in many persons with RA, this information is important for rheumatology professionals when dealing with persons with RA in routine care.
27239931 [Pulmonary fibrosis as the first manifestation of scleroderma systematica overlap syndrome 2016 The paper describes a clinical case of a female patient with signs of visceral scleroderma systematica and rheumatoid arthritis (RA). Interstitial pulmonary fibrosis was the first manifestation of overlap syndrome. The articular and cutaneous of the syndrome were moderate and cast doubts upon whether the systemic rheumatic disease was present. Postmortem examination confirmed the presence of pulmonary fibrosis, scleroderma, and RA. The case is of interest from the point of view of the atypical onset of the disease.