Browse

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

ID PMID Title PublicationDate abstract
26568849 Sexual Self-Concept and General Health in Rheumatoid Arthritis Patients. 2015 Oct BACKGROUND: There are several studies regarding sexual dysfunction in chronic diseases such as diabetes and renal failure; however, no significant study has been done on Iranian rheumatoid arthritis (RA) patients. OBJECTIVES: In this study, we aimed to identify and compare sexual dysfunction between RA patients and the normal population. PATIENTS AND METHODS: In this case-control study, two groups of females (87 RA patients and 89 controls) were randomly selected from the rheumatology clinic of Baqiyatallah Hospital, Tehran, Iran. General health questionnaire (GHQ-28) and multidimensional sexual self-concept questionnaire (MSSCQ) were used to evaluate RA patients. We used SPSS for statistical analysis mainly by the t-test and chi-square test. P values less than 0.05 were considered significant. RESULTS: In the GHQ-28 evaluation, RA patients had lower social function; however somatization rated higher in normal patients (P < 0.05). Sexual health was lower in the RA population (P < 0.05). No significant difference was found in sexual desire. Except sexual pain, other sexual health parameters were lower in RA patients. The scores were as follow: sensation 13.6 ± 4.4 vs. 12.2 ± 4.5, P = 0.024; lubrication 6.9 ± 2.1 vs. 6.2 ± 2.1, P = 0.017; orgasm 10.4 ± 2.8 vs. 9.5 ± 3.2, P = 0.37; pain 10.1 ± 2.2 vs. 10.8 ± 1.9, P = 0.013; enjoyment 23.8 ± 5.8 vs. 21.3 ± 7.5, P = 0.009 and partner related 8.5 ± 1.7 vs. 7.6 ± 2.4, P = 0.005. Furthermore, the concern of losing their sexual partner was higher in the normal population. CONCLUSIONS: Our study demonstrated that almost all GHQ and MSSCQ parameters were lower in RA patients, which indicates lower quality sexual life in RA patients. We recommend further consideration for the treatment and care of these patients.
26529931 [Anti-RANKL antibody]. 2015 Oct RANKL (receptor activator of nuclear factor-κB ligand) critically regulates the differentiation, activation, and survival of the osteoclast, and the hyperactivation of the RANKL-RANK signaling pathway leads to osteoporosis. Denosumab is a complete human monoclonal antibody against human RANKL, and suppresses bone resorption by inhibiting the interaction between RANKL and RANK. Accumulating evidence has demonstrated the clinical usefulness of denosumab on postmenopausal osteoporosis. Although the effectiveness of denosumab on disease activity of rheumatoid arthritis has not been clarified yet, previous studies reported that denosumab significantly increased the bone density of lumbar spine and proximal femur of rheumatoid arthritis patients.
27818127 Novel n-3 PUFA monoacylglycerides of pharmacological and medicinal interest: Anti-inflamma 2016 Dec 5 Newly-synthesized, eicosapentaenoic acid monoacylglyceride (MAG-EPA), docosahexaenoic acid monoacylglyceride (MAG-DHA) and docosapentaenoic acid monoacylglyceride (MAG-DPA) have been demonstrated to display beneficial effects in several disorders including chronic airway inflammatory diseases, pulmonary hypertension, rheumatoid arthritis, and lung and colorectal adenocarcinoma. Recent evidence reveals that omega-3 polyunsaturated fatty acid (n-3 PUFA) precursors provide a window to explore the pathobiology of inflammatory disease as well as structural templates for the design of novel pro-resolving precursors that are well absorbed by the gastrointestinal (GI) tract and metabolized into bioactive metabolites. These metabolites are found in blood circulation and tissues thereby mediating numerous immuno-modulatory effects through the activation of specific receptors. Bioactive metabolites regulate cell membrane functions, lipid signaling and gene expressions encoding for enzymes responsible for lipid storage and fatty acid metabolism. This review highlights recent experimental findings regarding n-3 PUFA monoacylglyceride research, as well as the pharmacological and medicinal relevance of these stereospecific derivatives in the resolution of chronic inflammatory diseases.
26800663 [Translational research in pediatric rheumatology. Current research approaches to the inna 2016 Apr Translational research aims at closely linking basic research and clinical observations so that important mechanistic insights identified in one field should trigger progress in the other. Particularly in the field of pediatric rheumatology this approach has significantly improved the understanding and therapy of several diseases in recent years. One focus of our research in this respect is on the structure, release mechanisms and function of damage associated molecular patterns (DAMP), particularly S100 proteins. Due to their huge potential as inflammation biomarkers for more specific diagnostics these proteins are of particular clinical interest. Overactivated cells of the innate immune system play a crucial role in the development of rheumatic diseases. Innate mechanisms, such as the generation of neutrophil extracellular traps (NETosis) were linked to the pathogenesis of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, it became increasingly more evident that various excessive sterile inflammatory mechanisms and reactions significantly contribute to an activation of adaptive immune responses and thus to the development of autoimmunity. Studying such potentially DAMP-dependent pathways at the interface between innate and adaptive immunity can provide a better understanding of autoinflammatory conditions in pediatric rheumatology and to identify novel targets for optimization of therapy.
27867381 A Critical Reappraisal of Neutrophil Extracellular Traps and NETosis Mimics Based on Diffe 2016 NETosis, an antimicrobial form of neutrophil cell death, is considered a primary source of citrullinated autoantigens in rheumatoid arthritis (RA) and immunogenic DNA in systemic lupus erythematosus (SLE). Activation of the citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is believed to be essential for neutrophil extracellular trap (NET) formation and NETosis. PAD4 is therefore viewed as a promising therapeutic target to inhibit the formation of NETs in both diseases. In this review, we examine the evidence for PAD4 activation during NETosis and provide experimental data to suggest that protein citrullination is not a universal feature of NETs. We delineate two distinct biological processes, leukotoxic hypercitrullination (LTH) and defective mitophagy, which have been erroneously classified as "NETosis." While these NETosis mimics share morphological similarities with NETosis (i.e., extracellular DNA release), they are biologically distinct. As such, these processes can be readily classified by their stimuli, activation of distinct biochemical pathways, the presence of hypercitrullination, and antimicrobial effector function. NETosis is an antimicrobial form of cell death that is NADPH oxidase-dependent and not associated with hypercitrullination. In contrast, LTH is NADPH oxidase-independent and not bactericidal. Rather, LTH represents a bacterial strategy to achieve immune evasion. It is triggered by pore-forming pathways and equivalent signals that cumulate in calcium-dependent hyperactivation of PADs, protein hypercitrullination, and neutrophil death. The generation of citrullinated autoantigens in RA is likely driven by LTH, but not NETosis. Mitochondrial DNA (mtDNA) expulsion, the result of a constitutive defect in mitophagy, represents a second NETosis mimic. In the presence of interferon-α and immune complexes, this process can generate highly interferogenic oxidized mtDNA, which has previously been mistaken for NETosis in SLE. Distinguishing NETosis from LTH and defective mitophagy is paramount to understanding the role of neutrophil damage in immunity and the pathogenesis of human diseases. This provides a framework to design specific inhibitors of these distinct biological processes in human disease.
27774822 Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2. 2017 Feb Janus kinases (JAKs) are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) that are critical in cytokine signalling and are strongly linked to both cancer and inflammatory diseases. There are currently two launched JAK inhibitors for the treatment of human conditions: tofacitinib for Rheumatoid arthritis (RA) and ruxolitinib for myeloproliferative neoplasms including intermediate or high risk myelofibrosis and polycythemia vera. Areas covered: This review covers patents claiming activity against one or more JAK family members in the period 2013-2015 inclusive, and covers 95 patents from 42 applicants, split over two parts. The authors have ordered recent patents according to the primary applicant's name, with part 2 covering J through Z. Expert opinion: Inhibition of JAK-family kinases is an area of growing interest, catalysed by the maturity of data on marketed inhibitors ruxolitinib and tofacitinib in late stage clinical trials. Many applicants are pursuing traditional fast-follower strategies around these inhibitors, with a range of chemical strategies adopted. The challenge will be to show sufficient differentiation to the originator compounds, since dose limiting toxicities with such agents appear to be on target and mechanism-related and also considering that such agents may be available as generic compounds by the time follower agents reach market.
27183937 Burden of rheumatological disorders in a tertiary care hospital. 2016 May OBJECTIVE: T To evaluate the frequency of different rheumatological disorders in patients visiting a tertiary care centre. METHODS: The retrospective analysis was conducted at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre, Karachi, and comprised prospectively collected data of patients with different musculoskeletal disorders from February 2004 to February 2014. Detailed history, examination and laboratory investigations were recorded in a pre-designed structured proforma. The frequency, demographic characteristics and associated co-morbidities were studied. SPSS 17 was used for statistical analysis. RESULTS: Of the 603 patients whose data was analysed, 460(76.3%) were women and 143(23.7%) were men. Overall mean age of the patients was 35.2±12 years. Rheumatoid arthritis was diagnosed in 458(76%) patients, systemic lupus erythematosus in 42(7%) ankylosing spondylitis in 32(5.3%), mixed connective tissue disease in 22(3.6%) and scleroderma in 12(2%) patients. CONCLUSIONS: Rheumatological disorders constitute a major disease burden in a relatively young population of patients. RA was the most common disorder seen in our clinic, as seen elsewhere also, followed by SLE, AS, MCTD, etc.
28553545 Rheumatic autoimmune diseases in women and midlife health. 2015 Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (scleroderma) preferentially affect women, and are characterized by systemic inflammation leading to target organ dysfunction. The public health burden of autoimmune diseases, which collectively represent a leading cause of morbidity and mortality among women throughout adulthood, is substantial. While some features of these diseases have been observed to improve over the menopausal transition, such as disease flare rate in SLE and skin softening and thinning in scleroderma, others, such as swollen and tender joints and radiographically confirmed damage in RA may worsen. The general trends, however, are not consistent or conclusive for all disease-related manifestations. Of great importance is the recognition that comorbid diseases, including osteoporosis and accelerated cardiovascular disease, contribute excess morbidity and mortality that becomes increasingly apparent as women with autoimmune diseases undergo the menopausal transition.
27747534 Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data f 2015 Dec INTRODUCTION: The goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis. METHODS: The percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated. RESULTS: Among 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6-33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3-14.8). CONCLUSION: In this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry. FUNDING: Corrona, LLC.
27335660 Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in 2016 OBJECTIVE: To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. DESIGN: Prospective, open-label, long-term mechanism of action study. SETTING: University clinic. METHODS: MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6-36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. RESULTS: Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=-0.63, p=0.007). CONCLUSIONS: MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion.
26958364 Association of a multibiomarker disease activity score at multiple time-points with radiog 2016 OBJECTIVES: In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up. METHODS: A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2. RESULTS: Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30-44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy. CONCLUSIONS: Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP. TRIAL REGISTRATION NUMBER: NCT00764725.
28348775 Progressive multifocal leukoencephalopathy and black fungus in a patient with rheumatoid a 2016 Aug INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating brain infection caused by JC polyomavirus (JCV), primarily seen in patients with severely compromised cellular immunity. Clinical presentation varies depending on the affected white matter. PML prognosis is variable and effective treatments are lacking. CASE PRESENTATION: A 75-year-old Chinese woman with type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis, treated with low-dose methotrexate and prednisolone for 2.5 years, developed a Pleurostomophora richardsiae infection of her left arm. After 6 months of treating this rare black fungus infection with voriconazole, surgery and immunosuppression discontinuation, she presented with progressive afebrile encephalopathy with right-sided hemiparesis. There were no signs of inflammation or metabolic abnormalities. Brain magnetic resonance imaging revealed diffuse frontal white matter lesions and a cerebrospinal fluid PCR confirmed PML due to JC virus. Severe lymphopenia was never present, and at PML diagnosis, CD4 and CD8 T-cell counts were 454 mm(-3) and 277 mm(-3). CD8 T-cells were able to respond to JCV VP1 peptide stimulation with TNFα secretion. Peripheral B-cell count was only 8 mm(-3). Mirtazapine and Maraviroc were started, but unfortunately, she rapidly deteriorated and died 5 weeks after PML diagnosis. CONCLUSION: Although peripheral lymphocyte counts were never low and CD4 T-cell count was close to normal, the persistent black fungus infection was a hallmark of severely compromised cellular immunity. The unexpected extremely low absolute B-cell count might suggest a protective role for B-cells. The paradoxical, clinical PML onset months after immunosuppressive discontinuation suggests that it was only discovered in the context of an immune reconstitution inflammatory syndrome.
27882112 Diagnostic value of high-frequency ultrasound and magnetic resonance imaging in early rheu 2016 Nov Early diagnosis and management improve the outcome of patients with rheumatoid arthritis (RA). The present study explored the application of high-frequency ultrasound (US) and magnetic resonance imaging (MRI) in the detection of early RA. Thirty-nine patients (20 males and 19 females) diagnosed with early RA were enrolled in the study. A total of 1,248 positions, including 858 hand joints and 390 tendons, were examined by high-frequency US and MRI to evaluate the presence of bone erosion, bone marrow edema (BME), synovial proliferation, joint effusion, tendinitis and tendon sheath edema. The imaging results of the above abnormalities, detected by US, were compared with those identified using MRI. No statistically significant overall changes were observed between high-frequency US and MRI in detecting bone erosion [44 (5.1%) vs. 35 (4.1%), respectively; P>0.05], tendinitis [18 (4.6%) vs. 14 (1.5%), respectively; P>0.05] and tendon sheath edema [37 (9.5%) vs. 30 (7.7%), respectively; P>0.05]. Significant differences were observed between high-frequency US and MRI with regards to the detection of synovial proliferation [132 (15.4%) vs. 66 (7.7%), respectively; P<0.05] and joint effusion [89 (10.4%) vs. 52 (6.1%), respectively; P<0.05]. In addition, significant differences were identified between the detection of BME using MRI compared with high-frequency US (5.5 vs. 0%, respectively; P<0.05). MRI and high-frequency US of the dominant hand and wrist joints were comparably sensitive to bone erosion, tendinitis and tendon sheath edema. However, MRI was more sensitive in detecting bone marrow edema in early RA, while US was more sensitive in the evaluation of joint effusion and synovial proliferation. In conclusion, US and MRI are promising for the detection and diagnosis of inflammatory activity in patients with RA.
27747535 Influence of Continuing Medical Education on Rheumatologists' Performance on National Qual 2015 Dec INTRODUCTION: In recent years researchers have reported deficits in the quality of care provided to patients with rheumatoid arthritis (RA), including low rates of performance on quality measures. We sought to determine the influence of a quality improvement (QI) continuing education program on rheumatologists' performance on national quality measures for RA, along with other measures aligned with National Quality Strategy priorities. Performance was assessed through baseline and post-education chart audits. METHODS: Twenty community-based rheumatologists across the United States were recruited to participate in the QI education program and chart audits. Charts were retrospectively audited before (n = 160 charts) and after (n = 160 charts) the rheumatologists participated in a series of accredited QI-focused educational activities that included private audit feedback, small-group webinars, and online- and mobile-accessible print and video activities. The charts were audited for patient demographics and the rheumatologists' documented performance on the 6 quality measures for RA included in the Physician Quality Reporting System (PQRS). In addition, charts were abstracted for documentation of patient counseling about medication benefits/risks and adherence, lifestyle modifications, and quality of life; assessment of RA medication side effects; and assessment of RA medication adherence. RESULTS: Mean rates of documented performance on 4 of the 6 PQRS measures for RA were significantly higher in the post-education versus baseline charts (absolute increases ranged from 9 to 24% of patient charts). In addition, after the intervention, significantly higher mean rates were observed for patient counseling about medications and quality of life, and for assessments of medication side effects and adherence (absolute increases ranged from 9 to 40% of patient charts). CONCLUSION: This pragmatic study provides preliminary evidence for the positive influence of QI-focused education in helping rheumatologists improve performance on national quality measures for RA.
27651929 Induction maintenance with tumour necrosis factor-inhibitor combination therapy with disco 2016 OBJECTIVE: To determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with MTX monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn. METHODS: We performed a meta-analysis of trials using the initial combination of MTX+TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early rheumatoid arthritis (RA). A systematic literature search was performed for induction-maintenance randomised controlled trials (RCTs) where initial combination therapy was compared with MTX monotherapy in patients with clinically active early RA. Our primary outcome was the proportion of patients who achieved low disease activity (LDA; Disease Activity Score (DAS)28<3.2) and/or remission (DAS28<2.6) at 12-76 weeks of follow-up. A random-effects model was used to pool the risk ratio (RR) for LDA and remission and heterogeneity was explored by subgroup analyses. RESULTS: We identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy. The pooled RRs for achieving LDA and clinical remission at follow-up after withdrawal of TNFi were 1.41 (95% CI 1.05 to 1.89) and 1.34 (95% CI 0.95 to 1.89), respectively. There was significant heterogeneity between trials due to different treatment strategies, which was a limitation to this study. CONCLUSIONS: Initial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi.
29900979 Is 4-Hydroxynonenal a Predictive Parameter for the Development of Joint Erosion in Patient 2016 Mar OBJECTIVES: This study aims to evaluate serum 4-hydroxynonenal (4-HNE) levels and its clinical and radiological significance in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: The study included 40 patients (8 males, 32 females; mean age 51.4±11.2 years; range 24 to 72 years) with RA and 30 healthy controls (8 males, 32 females; mean age 53.0±11.7 years; range 24 to 72 years. Serum 4-HNE levels were measured using sandwich enzyme-linked immunosorbent assay method. Patients with disease activity score 28 ≤3.2 and >3.2 were allocated into low and high/moderate disease activity groups, respectively. Additionally, patients were divided into two groups as early RA (disease duration ≤2 years) and established RA (disease duration ≥2 years). Functional disability was evaluated using health assessment questionnaire. Radiographs were scored using the modified Larsen scoring. RESULTS: Serum 4-HNE levels in patients with RA were significantly higher than controls (p=0.001). Serum 4-HNE levels did not correlate with laboratory or clinical parameters of disease activity including erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, and health assessment questionnaire. Serum 4-HNE levels were higher in patients with established RA than patients with early RA (r=0.487, p=0.001). Besides, modified Larsen score which indicates structural damage correlated significantly with serum 4-HNE levels (p=0.001). CONCLUSION: These results indicate that serum 4-HNE levels may be used as an indicator for structural damage such as erosions in the early stage of RA; however, they are not efficient to monitor disease activity.
26535151 Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibito 2015 OBJECTIVES: To study the number of patients that taper or discontinue concomitant methotrexate (MTX) in daily practice in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor inhibitor (TNFi) and to analyse the effects of that adaption on disease activity and drug survival. METHODS: Data were collected from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Patients who started their first TNFi were included in the study. Treatment effectiveness after MTX tapering or discontinuation was analysed using Disease Activity Score of 28 joints (DAS28). Drug survival of the TNFi was analysed using the Cox proportional hazard model with a time-dependent covariate. RESULTS: In 458 patients (34%), MTX was tapered, 126 patients (10%) discontinued MTX and 747 patients (56%) continued MTX at the same dose. On average, DAS28 improved after tapering MTX (-0.40, -0.45) and after stopping MTX (-0.28, -0.12) at 6 and 12 months. In the taper group, 21% of the patients relapsed (DAS28 increase >0.6), and in the discontinuation group this was 21% and 24% at 6 and 12 months, respectively. Patients who taper and discontinue MTX have a similar DAS28 score over time as patients who continue MTX. Moreover, there was no influence of tapering or discontinuation of MTX on long-term drug survival of TNFi. CONCLUSIONS: In daily practice, tapering or discontinuation of concomitant MTX in patients with RA treated with TNFi frequently occurs and it does not seem to influence the average DAS28 over time or the long-term TNFi drug survival. It appears that in daily clinical practice the correct patients are selected to taper or discontinue MTX.
27407255 Assessment of the usefulness of skin autofluorescence as an indicator of disease activity 2015 OBJECTIVES: Diabetes develops much more often in patients suffering from rheumatoid arthritis (RA) than in healthy population. One of the parameters which allow to evaluate the risk of developing diabetes and cardiovascular diseases (CVD) is the level of advanced glycation end products (AGE) in the skin. In patients suffering from RA, an increase in AGE level may be also linked with the course of the underlying disease. The aim of the study was to evaluate the correlation between the AGE level and the course of RA as well as other risk factors for the development of diabetes and CVD. MATERIAL AND METHODS: The study included 148 patients divided into three groups: group I - patients with RA (n = 102, 79 F/23 M), group II - patients with RA and diabetes (n = 21, 14 F/7 M), group III - healthy individuals (n = 25, 16 F/9 M). Each patient underwent a skin autofluorescence signal (SAF) examination with an AGE Reader, which allows the assessment of AGE level, as well as being subjected to the laboratory tests panel. Additionally, patients from group I and II have had their DAS28 (ESR) indicator calculated. RESULTS: In groups I, II, and III, the respective mean SAF values, expressed in arbitrary units [au], were to 2.54, 2.74, and 1.96 au. Between-group differences in terms of mean SAF values were statistically significant (p < 0.05). CONCLUSIONS: Significantly higher mean SAF values in groups I and II as compared to group III suggest that the increase in the AGE level in patients with RA is linked with the underlying disease and does not have to correspond with the real risk of diabetes and CVD. In conclusion, despite the known limitations of the technique, measuring AGE levels allows for closer monitoring of RA patients who are at a higher risk of developing diabetes.
26004232 Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DN 2015 Aug In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ∼66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ∼9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases.
27844414 Treating the Underlying Pathophysiology of Primary Sjögren Syndrome: Recent Advances and 2016 Nov Sjögren Syndrome (SS) is a systemic autoimmune disease with a wide clinical spectrum that extends from sicca symptoms of the mucosal surfaces to extra-glandular systemic manifestations. Understanding of the pathophysiology of primary SS has advanced over recent years, and this, in turn, has presented new targeted treatment options. We provide a brief, up-to-date description of the pathophysiology of SS and the main etiopathogenic pathways implicated in the disease process and review clinical evidence in support of new treatment options targeting these pathways, highlighting successes and failures, and concluding with a summary of gaps in knowledge and where future research should be focused. Direct and indirect B-cell targeted therapies are currently the most promising biological agents in primary SS, especially for systemic involvement, but other pathways (T-cell co-stimulation, cytokine-based therapies, intracellular pathways and gene therapies) are under development. The next 10 years may witness a disruptive therapeutic scenario in primary SS.