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ID PMID Title PublicationDate abstract
28039541 Patient-reported outcomes in Asia: evaluation of the properties of the Rheumatoid Arthriti 2017 May Patient-reported outcomes (PROs) such as the Europe-developed Rheumatoid Arthritis Impact of Disease (RAID) are important to assess patients' quality of life. Their interpretation may be culture-dependent. To evaluate the potential utility of RAID in multiethnic Asian rheumatoid arthritis (RA) patients. Cross-sectional study of English-speaking RA patients in a Singapore tertiary center. Validity of RAID (scored between 0 and 10 with higher score indicating worse status) was assessed by Spearman's correlation with patient global assessment (PGA), DAS28 and short form 12 (SF-12). Consistency was assessed by Cronbach's alpha and test-retest reliability by intra-class correlation coefficient (ICC) 7 days after (n = 20). Feasibility was assessed by % of missing data. Eighty-two patients were analyzed: median age 53 years (Q1:Q3 44.7; 60.7), disease duration 4.2 years (1.4; 8.8), 66 (81%) women and 54 (66%) Chinese. Although RA was moderately active (median DAS28, 3.2 (2.5; 4.3)), RAID score was very low (median, 1.9 (0.6; 3.7)) with 44 (53.7%) patients having RAID score between 0 and 2. RAID was strongly correlated with PGA (r = 0.75), and moderately with other outcomes (DAS28 r = 0.46, SF12 physical r = -0.45 and SF12 mental r = -0.52, p < 0.0001 for all). Consistency was high (Cronbach's alpha = 0.91). Test-retest reliability was excellent; ICC = 0.84 (95% confidence interval 0.74-0.90). Feasibility was good with only 2 patients with missing data. Despite considerable floor effects, the RAID appeared to be a valid and practical PRO to assess the impact of RA in Asia. Multiethnic Asian patients may underestimate the impact of their disease compared to European patients.
27647009 Acute effect of Capparis spinosa root extracts on rat articular pain. 2016 Dec 4 ETHNOPHARMACOLOGICAL RELEVANCE: Capparis spinosa L. originates from dry regions of Asia and Mediterranean basin. In traditional medicine of these areas, infusions from caper root are considered to be beneficial for the treatment of rheumatism, gout and against abdominal pains. AIM OF THE STUDY: To evaluate the pain relieving properties of a Syrian cultivar of Capparis spinosa roots in rat models of osteoarthritis and rheumatoid arthritis. MATERIALS AND METHODS: Decoction (DEC) and hydroalcoholic extract (EtH(2)O) were obtained from powdered roots; the latter was further separated in CH(2)Cl(2) and aqueous (H(2)O-Res) fractions. The extracts were characterized in terms of spermidine alkaloids by HPLC/DAD/MS and stachydrine by NMR. Different amount of free and glycosilated forms of capparispine and analogues (from 0.5% w/w for DEC up to 7.6% w/w for CH(2)Cl(2) fraction) were detected. Rat models of rheumatoid arthritis and osteoarthritis were induced by the intra-articular administration of Complete Freund's Adjuvant (CFA) or monosodium iodoacetate (MIA), respectively. RESULTS: Fourteenth days after CFA or MIA injection, the different preparations of Capparis spinosa (3, 30, 100 and 300mgkg(-1)) were acutely administered p.o.. Powdered roots (300mgkg(-1)), DEC (100mgkg(-1)), and EtH(2)O (300mgkg(-1)) significantly reduced hypersensitivity to mechanical noxious stimuli as well as spontaneous pain evaluated as hind limb bearing alterations in both models. The CH(2)Cl(2) and the H(2)O-Res (30mgkg(-1)) were the most potent in reverting pain threshold alterations despite the different content of free alkaloids. CONCLUSIONS: Capparis spinosa extracts relieved pain related to rheumatoid arthritis and osteoarthritis after single administration. A synergistic effect due to a specific "phytochemical mixture" is suggested.
27367831 The correlations of socioeconomic status, disease activity, quality of life, and depressio 2017 Jan This study aimed (i) to investigate the relationships among socioeconomic status, disease activity, quality of life, and the psychological status in Chinese rheumatoid arthritis (RA) patients; (ii) to explore the possible risk factors of anxiety and depression. A total of 160 RA patients underwent standardized laboratory examinations and completed several questionnaires. Independent samples t-tests, χ(2) analyses, and logistic regression modeling were used to analyze the data. We found 30.6% RA patients were anxiety, and 27.5% had depression, which were significantly higher than the control group (7.8 and 11.7%, respectively). And there were significant correlations among education, pain, disease activity, medication adherence, functional capacity, quality of life, and anxiety/depression. Meanwhile, logistic regression analysis revealed that poor quality of life and low education level were significantly associated with anxiety/depression in RA patients. In conclusion, there were significant relationships among education, quality of life, and anxiety/depression in Chinese RA patients.
27564580 Can mean platelet volume and red blood cell distribution width show disease activity in rh 2016 Sep AIM: To evaluate the relationship between mean platelet volume (MPV) and red cell distribution width (RDW), and disease activity in rheumatoid arthritis (RA). PATIENTS & METHODS: Hundred RA and 100 controls were included. RESULTS: MPV and RDW were higher in RA (p < 0.0001). The cut-off levels of RDW and MPV were 14.8 and 10.4. Patients with RDW >14.8 had higher Disease Activity Score 28 (DAS28; p = 0.002) and pain score (p = 0.0007). RDW was positively correlated with DAS28 and pain. But, DAS28 and pain were not different between patients with MPV >10.4 and <10.4. CONCLUSION: MPV and RDW were significantly higher in RA. RDW and MPV were similar to erythrocyte sedimentation rate and C-reactive protein to indicate inflammatory activity. RDW was correlated with pain and DAS28, but MPV was not associated with them.
26360583 Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatme 2015 OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs)) for rheumatoid arthritis (RA). METHODS: We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR). RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naïve" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66) and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87), test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (β = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03). Analyses conducted using DAS28-remission as the outcome supported the above-mentioned findings. CONCLUSION: Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naïve and trials including patients with shorter disease durations.
25732812 Novel therapeutic targets in rheumatoid arthritis. 2015 Apr Rheumatoid arthritis (RA) is an autoimmune disease that leads to inflammation and destruction of synovial joints. Despite the broad spectrum of antirheumatic drugs, this heterogeneous disease is still not well controlled in up to 30% of patients. Here, we discuss two pathways that are regarded as interesting novel therapeutic targets in the field of rheumatology: the Janus kinase (JAK) pathway and the T helper-17 (Th17) pathway [including interleukin (IL)-17, IL-21, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. We also review the therapy potential of biologicals and small-molecule inhibitors blocking these pathways. Advances in combination therapy in addition to progress in biomarker screening will help us to further achieve effective and personalized healthcare for patients with RA.
29624032 [VAGAL NERVE STIMULATION IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS – RESULT 2016 OBJECTIVE: Electrical stimulation of the vagus has proven effective in various inflammatory conditions in animal models. The aim of this study is to show the effect of vagal nerve neurostimulation on clinical and laboratory parameters in two patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate. PATIENTS AND METHODS: The research was conducted as part of an international pilot study. Patients were implanted with the Cyberonics system for electrical stimulation of the vagus. After an initial in-clinic stimulation, the patients performed the stimulations at home for 42 days, when the device was inactivated. On day 56 the stimulations were reinitiated. The following parameters were evaluated: tender and swollen joint count, physician’s (PGA) and patient’s (PtGA) global score, intensity of pain, disease activity (DAS28), functional ability (HAQ), serum CRP level, and EULAR response. RESULTS: In the period from the screening visit to the day 42 visit, both patients experienced an improvement of DAS28 (7.00 and 6.22 vs. 4.03 and 2.13), PGA (70 and 53 vs. 27 and 16), PtGA (48 and 43 vs. 15 and 14), tender joint count (26 and 28 vs. 4 and 0), swollen joint count (24 and 14 vs. 8 and 2), intensity of pain (72 and 87 vs 21 and 7), HAQ score (2.25 and 2.25 vs. 1.5 and 1.375), and CRP levels (23.8 and 5.58 vs. 13 and 4.61). After the device deactivation, DAS28 and VAS pain worsened in both patients. CONCLUSION: Vagal neural stimulation in the treatment of patients with active RA and an inadequate response to methotrexate is effective in reducing clinical symptoms and parameters of inflammation. Our results are in accordance with the results obtained in other centers. Research on a larger number of subjects is necessary for a better evaluation of the effect of this new approach to the treatment of patients with rheumatoid arthritis.
26374955 Prevalence of chronic kidney disease and administration of RA-related drugs in patients wi 2016 OBJECTIVES: To estimate the prevalence of chronic kidney disease in patients with rheumatoid arthritis (RA) and the administration of disease-modifying anti-rheumatic-drugs (DMARDs), using data from the National Database of Rheumatic Disease by iR-net in Japan (NinJa) 2012 study. METHODS: From a total of 11,940 RA patients, 7135 who underwent an estimated glomerular filtration rate (eGFR) test were studied. Renal dysfunction staging was assessed using Japanese eGFR equations and classified according to the Kidney Disease Improving Global Outcomes 2012 clinical practice guideline. RESULTS: The prevalence of GFR stages was as follows: stage G1, 25.4%; stage G2, 55.9%; stage G3, 17.5%; stage G4, 0.8%; and stage G5, 0.2%. Overall, 92.7% of patients received at least one DMARD. Sulfasalazine, tacrolimus, and biologics (except inflixmab) were administered in all GFR stages. Methotrexate was not prescribed in patients with stage G5, but methotrexate 3.5 mg/week (mean) was prescribed in four patients (6.8%) with stage G4. Non-steroidal anti-inflammatory drugs and glucocorticoids were prescribed in 40.5% and 43.7% of patients, respectively. CONCLUSION: The prevalence of kidney disease in this large sample of RA patients was higher than that in the general population, and the results suggest that RA patients with renal dysfunction require careful drug selection.
27490206 Cardiovascular risk assessment in patients with rheumatoid arthritis: The relevance of cli 2016 Nov Cardiovascular disease (CV) is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). This is the result of an accelerated atherosclerotic process. Adequate CV risk stratification has special relevance in RA to identify patients at risk of CV disease. However, current CV risk screening and management strategies underestimate the actual CV risk in RA. Consequently, the search for additional tools that may help to identify those patients at high CV risk has become a key objective in the last years. In this regard, non-invasive surrogates, such as carotid ultrasonography, have been found to be excellent predictors of future CV events. In addition, several studies have revealed the relevance of a genetic component in the development of CV disease in RA patients. Besides an association with HLA-DRB1* shared epitope alleles other gene polymorphisms located inside and outside the HLA seem to influence the risk of cardiovascular disease in RA. Moreover, serum levels of some metabolic syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of endothelial cell activation and inflammation such as Osteoprotegerin and Asymmetric dimethylarginine have recently been found useful for the prediction of CV disease in these patients. An update of the current knowledge on these potential markers, especially focused on new genetic and serological biomarkers is shown in this review.
26686848 Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian 2016 Jan Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.
26226010 The role of genetic variants in CRP in radiographic severity in African Americans with ear 2015 Oct This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.
27050469 Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to Infliximab 2016 Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05), representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40). This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023). On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and indicate that they are notably drug-specific.
26163688 The impact of multimorbidity status on treatment response in rheumatoid arthritis patients 2015 Nov OBJECTIVE: When treating RA patients, remission (REM) or at least low disease activity (LDA) is the ultimate therapeutic goal. The aim of this study was to assess the impact of multimorbidity on achieving REM or LDA. METHODS: In a prospective RA cohort, we identified patients initiating any DMARD with follow-up data 1 year after. Treatment effects were measured using the clinical disease activity index (CDAI) and the modified health assessment questionnaire (MHAQ); multimorbidity status was assessed using a counted multimorbidity index (cMMI). The proportion of patients reaching REM or LDA 1 year after DMARD commencement with respect to the cMMI was evaluated. In regression models, we calculated the odds ratio of achieving REM or LDA, and predicted CDAI and MHAQ 1 year after DMARD commencement for various levels of cMMI, adjusting for age, sex, disease duration, serostatus, disease activity at DMARD commencement, number of previous DMARDs, and type of DMARD, steroid and NSAID use. RESULTS: A total of 815 patients started DMARDs; 414 were on the same DMARD after 1 year. The proportion of these patients achieving REM or LDA after 1 year was significantly lower in the patients with higher cMMI, following a linear trend (P < 0.01). After accounting for covariates, the odds ratio for REM associated with each additional morbidity in the cMMI was 0.72 (95% CI 0.55, 0.97) and 0.81 (95% CI 0.70, 0.94) for LDA. One year after DMARD initiation, CDAI (+0.16 per additional morbidity) and MHAQ scores (+0.15 per additional morbidity) were significantly worse (both P < 0.05). CONCLUSION: Increased multimorbidity negatively affects the therapeutic goal of REM and LDA.
26033326 Efficacy of inhibition of IL-1 in patients with rheumatoid arthritis and type 2 diabetes m 2015 Jun 2 INTRODUCTION: Rheumatoid arthritis is an autoimmune arthritis in which two inflammatory cytokines, tumor necrosis factor-α and interleukin-1β, play a critical role in the induction and progression of the disease. Several reports and data from registries have discussed the association between chronic inflammatory diseases and disorders in intermediary metabolism, pointing out that prevalence of peripheral insulin resistance and type 2 diabetes mellitus is increased among patients with rheumatoid arthritis. In addition, several studies have shown that type 2 diabetes mellitus may be considered an interleukin-1β inflammatory-mediated process, and both preclinical and clinical observations have reported the usefulness of interleukin-1 antagonism therapy in this disease. CASE PRESENTATION: We describe the case of a 58-year-old Caucasian woman and a 74-year-old Caucasian man with rheumatoid arthritis associated with type 2 diabetes mellitus. In these patients, the inhibition of interleukin-1β not only induced remission for rheumatoid arthritis, but successfully controlled their metabolic status. CONCLUSIONS: We report the positive effects of the inhibition of interleukin-1 in two patients with rheumatoid arthritis associated with type 2 diabetes mellitus, with both reaching the therapeutic targets of their diseases by using a single biological agent and tapering or discontinuing their antidiabetic therapies. These findings suggest that targeting interleukin-1 might be considered a good therapeutic option for the treatment of rheumatoid arthritis associated with type 2 diabetes mellitus.
27558398 Can baseline serum microRNAs predict response to TNF-alpha inhibitors in rheumatoid arthri 2016 Aug 24 BACKGROUND: In rheumatoid arthritis, prediction of response to TNF-alpha inhibitor (TNFi) treatment would be of clinical value. This study aims to discover miRNAs that predict response and aims to replicate results of two previous studies addressing this topic. METHODS: From the observational BiOCURA cohort, 40 adalimumab- (ADA) and 40 etanercept- (ETN) treated patients were selected to enter the discovery cohort and baseline serum profiling on 758 miRNAs was performed. The added value of univariately selected miRNAs (p < 0.05) over clinical parameters in prediction of response was determined by means of the area under the receiver operating characteristic curve (AUC-ROC). Validation was performed by TaqMan single qPCR assays in 40 new patients. RESULTS: Expression of miR-99a and miR-143 predicted response to ADA, and miR-23a and miR-197 predicted response to ETN. The addition of miRNAs increased the AUC-ROC of a model containing only clinical parameters for ADA (0.75 to 0.97) and ETN (0.68 to 0.78). In validation, none of the selected miRNAs significantly predicted response. miR-23a was the only overlapping miRNA compared to the two previous studies, however inversely related with response in one of these studies. The reasons for the inability to replicate previously proposed miRNAs predicting response to TNFi and replicate those from the discovery cohort were investigated and discussed. CONCLUSIONS: To date, no miRNA consistently predicting response to TNFi therapy in RA has been identified. Future studies on this topic should meet a minimum of standards in design that are addressed in this study, in order to increase the reproducibility.
25879438 Do patient-reported outcome measures cover personal factors important to people with rheum 2015 Feb 25 BACKGROUND: Personal factors (PFs) are internal factors that determine functioning and the individuals' experience of disability. Their coverage by patient-reported outcome measures (PROMs) has not been examined in rheumatoid arthritis (RA) so far. The aims of this study were to identify PFs important in the life stories of people with RA and to determine their coverage by PROMs used in RA. METHODS: The qualitative data of people with RA was explored to identify PFs. Additionally a systematic literature search was conducted to find PROMs used in RA. PROMs items were linked to the components, domains and categories of the International Classification of Functioning, Disability and Health (ICF) to determine the coverage of important PFs by PROMs. RESULTS: Twelve PFs were found to be important in the life stories of people with RA. The PFs coping and reflecting about one's life in an optimistic way were covered most frequently, each by 14 of the 42 explored PROMs, while job satisfaction was not covered at all. The London Coping with Rheumatoid Arthritis Questionnaire, General Self-Efficacy Scale, Arthritis Self-Efficacy Scale, Rheumatoid Arthritis Self-Efficacy Questionnaire and Revised Ways of Coping Inventory covered most PFs. Nineteen PROMs did not cover any of the PFs. CONCLUSION: Several PFs were identified as important in the life stories of people with RA, but only 55% of the PROMS covered some of these PFs. When evaluating PFs important to people with RA, health professionals should be alert on which PROMs can be used to assess which PFs.
26834212 Clinical Characteristics and Cytokine Profiles of Organizing Pneumonia in Patients with Rh 2016 Apr OBJECTIVE: It has been reported that organizing pneumonia (OP) develops when patients with rheumatoid arthritis (RA) are treated with biologic disease-modifying antirheumatic drugs (bDMARD). However, the clinical characteristics and pathophysiology of OP in RA remain unknown in patients treated with bDMARD. We investigated the clinical characteristics and cytokine profiles of patients with RA-OP treated with bDMARD or conventional synthetic DMARD (csDMARD). METHODS: Twenty-four patients with RA who had developed OP were enrolled. These patients included 12 treated with bDMARD (bDMARD-OP subset) and 12 treated with csDMARD (csDMARD-OP subset). We compared the clinical characteristics and cytokine profiles between the patients with OP (OP subset, n = 24) and non-OP patients (non-OP subset, n = 29). RESULTS: There was no significant difference in clinical characteristics between the OP subset and the non-OP subset. Four patients developed OP within 2 months of bDMARD administration. In the other 8 patients, OP developed more than 1 year after the initiation of bDMARD. OP improved with corticosteroid treatment in all bDMARD-OP patients. After OP improved, bDMARD were readministered in 6 patients, and no OP recurrence was observed in any of these patients. Our multivariate analysis revealed that serum levels of interferon-α (IFN-α), interleukin (IL)-1β, IL-6, IL-8, and interferon-γ-inducible protein 10 were significantly associated with the development of OP, although these cytokines tended to be lower in the bDMARD-OP subset than in the csDMARD-OP subset. CONCLUSION: OP is unlikely to be fatal in patients treated with bDMARD or csDMARD. IFN-α and proinflammatory cytokines are associated with the pathophysiology of OP in RA.
25073879 Analysis of integrated radiographic data from two long-term, open-label extension studies 2015 Feb OBJECTIVE: A longitudinal integration approach evaluated all radiographic scores assessed over 10 years, rather than only completer data, from 2 studies of adalimumab (ADA) for rheumatoid arthritis (RA). METHODS: The DE019 (methotrexate [MTX]-inadequate responders, longstanding RA) and PREMIER (MTX-naive, early RA) studies, respectively, had 1- or 2-year double-blind periods followed by 9- or 8-year open-label extensions (OLEs). Patients received ADA ± MTX in both OLEs. Radiographic progression was assessed using change from baseline in modified total Sharp score (ΔmTSS). A mixed-effects model was used post hoc to evaluate repeated measurements of different data campaigns and to estimate ΔmTSS through up to 10 years of treatment based on original randomization groups (placebo [PBO] + MTX or standard dose ADA + MTX). RESULTS: Data from patients with baseline and ≥1 postbaseline radiograph were included (n = 327 for DE019; n = 452 for PREMIER). Integrated and 10-year completer ΔmTSS progression curves differed slightly. In DE019, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 6.6 units (integrated model) and 6.2 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 0.9 units by integrated analysis and 0.7 units in completers. In PREMIER, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 11.2 units (integrated analysis) and 11.0 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 5.1 units (integrated analysis) and 4.0 units (completers). A higher radiographic progression rate was observed in patients who received delayed versus immediate ADA + MTX treatment. CONCLUSIONS: Longitudinal integrated analysis provided robust estimates of radiographic progression that only slightly differed from completers-only scores and confirmed the effects.
27908300 Serum complement C3 strongly correlates with whole-body insulin sensitivity in rheumatoid 2017 Jan OBJECTIVES: Rheumatoid arthritis (RA) is characterised by an excess of cardiovascular diseases (CVD) risk, attributable to a synergy between under-diagnosed traditional risk factors (i.e. insulin resistance) and inflammatory disease activity. The aim of the present study was to evaluate the correlation between inflammatory measures and insulin sensitivity in RA patients. METHODS: Forty non-diabetic RA patients (19 males) were recruited. All patients underwent anthropometric measurements, laboratory evaluation and oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI) was calculated with the equation proposed by Matsuda et al., from dynamic values of glucose and insulin obtained during OGTT. RESULTS: In the univariate analysis, lnISI correlated inversely with age, BMI, waist circumference, sBP, ESR, lnCRP and complement C3, but not with disease duration, dBP or complement C4. In non-obese patients (BMI <30 kg/m2, n=28), only age, BMI, lnCRP and C3 maintained their correlation with lnISI. In a stepwise multiple regression using lnISI as the dependent variable and BMI, age, lnCRP and complement C3 as predictors, only BMI and C3 entered the equation and accounted for 38.2% of the variance in lnISI. In non-obese patients, only C3 entered the regression equation, accounting for 32.2% of the variance in lnISI. Using a ROC curve, we identified the best cut-off for complement C3 of 1.22 g/L that yielded a sensitivity of 67% and a specificity of 79% for classification of insulin resistant patients. CONCLUSIONS: In RA patients, complement C3 correlates strongly with insulin sensitivity, in both obese and non-obese individuals.
25766525 Mitomycin C induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via a m 2015 BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. METHODS: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. RESULTS: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. CONCLUSION: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway.