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ID PMID Title PublicationDate abstract
28390560 Reproductive Health Screening in Women with Autoimmune Diseases. 2017 May Although the female predominance of autoimmune diseases is not completely understood, sex hormones are thought to play a role. Attention to lifelong reproductive health is especially important for women with autoimmune disorders. Many of these women require long-term immunosuppressive therapy that may affect their ability to clear infections, including viruses, and may alter natural tumor surveillance mechanisms. As a result, women with autoimmune diseases may have different risks for common reproductive-related malignancies that may in turn affect screening guidelines and other preventive measures, including vaccination. Women with autoimmune diseases need to adhere diligently to screening recommendations.
27999943 Long-term use of biologic agents does not increase the risk of serious infections in elder 2017 Mar This study aimed to determine whether the long-term use of biologic agents increases serious infections in elderly patients with rheumatoid arthritis (RA) and to determine the risk factors of serious infections in biologics-treated elderly RA patients. We retrospectively analyzed the incidence rate of serious infections that required hospitalization between biologics-treated and non-biologic disease-modifying antirheumatic drug (DMARD)-treated elderly RA patients (aged over 65 years). We examined the risk factors for serious infections in biologics-treated elderly RA patients. We found that, during a 3-year observation period, the incidence rate of serious infections was not significantly different between biologics-treated and non-biologic DMARD-treated elderly RA patients [8.0 (95% CI 4.7-13.5) and 6.3 (95% CI 4.1-9.5) events per 100 person-years of follow-up, respectively, P = 0.78]. The time to the first serious infection did not significantly differ between the two groups by the analysis of the Kaplan-Meier curves, either (P = 0.46). We then found that prednisolone doses alone were significantly associated with serious infections in biologics-treated elderly RA patients. Furthermore, we found that prednisolone at 1-4 mg/day was associated with serious infections in biologics-treated patients, but not non-biologic DMARD-treated patients. On the other hand, prednisolone at greater than 5 mg/day was associated with serious infections in both biologics-treated and non-biologics-treated patients. We show that there is not a significant difference between the incidence of serious infections between biologics group and non-biologics group in elderly RA patients (≧65 years) and that even very low-dose glucocorticoid use (prednisolone 1-4 mg/day) is a risk factor for serious infections in biologics-treated elderly RA patients.
27895040 The role of non-invasive cardiovascular imaging in the assessment of cardiovascular risk i 2017 Jul This review assesses the risk assessment of cardiovascular disease (CVD) in rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve risk stratification in future. RA is common and patients are at greater risk of CVD than the general population. Cardiovascular (CV) risk stratification is recommended in European guidelines for patients at high and very high CV risk in order to commence preventative therapy. Ideally, such an assessment should be carried out immediately after diagnosis and as part of ongoing long-term patient care in order to improve patient outcomes. The risk profile in RA is different from the general population and is not well estimated using conventional clinical CVD risk algorithms, particularly in patients estimated as intermediate CVD risk. Non-invasive imaging techniques may therefore play an important role in improving risk assessment. However, there are currently very limited prognostic data specific to patients with RA to guide clinicians in risk stratification using these imaging techniques. RA is associated with increased risk of CV mortality, mainly attributable to atherosclerotic disease, though in addition, RA is associated with many other disease processes which further contribute to increased CV mortality. There is reasonable evidence for using carotid ultrasound in patients estimated to be at intermediate risk of CV mortality using clinical CVD risk algorithms. Newer imaging techniques such as cardiovascular magnetic resonance and CT offer the potential to improve risk stratification further; however, longitudinal data with hard CVD outcomes are currently lacking.
27575584 Effects of cold mist shower on patients with inflammatory arthritis: a crossover controlle 2017 May OBJECTIVES: To evaluate the safety and effects of a new home treatment method, a whole-body cold mist treatment, on patients with chronic inflammatory arthritis. METHOD: Whole-body cold mist shower therapy was given to 121 voluntary patients with chronic inflammatory arthritis in this crossover study during 1-week rehabilitation periods. Pain and sleep quality were assessed by a 10-cm visual analogue scale (VAS). Mental status was assessed by the Depression Scale (DEPS). Body temperature, blood pressure, heart rate, use of occasional pain and sleep medication, and possible side-effects were recorded. RESULTS: The differences in pain (VAS) between treatment and control periods were significant (2.0 vs. 2.4, p = 0.006, paired t-test) in the last measurement, when assessing the pain of the past week as a whole. A trend could be seen of an increasing difference towards the end of the week. The treatment effect was statistically significant [likelihood ratio test (LRT), p < 0.0001] after controlling for period and sequence effects. There was an indication of better sleep quality (VAS) during the treatment period (2.3 vs. 2.7, p = 0.058 paired t-test) when assessing the past week as a whole. The mean DEPS scores showed no difference between the treatment periods (5.5 vs. 5.0, p = 0.1874 paired t-test, at start, and 4.5 vs. 4.1 p = 0.29 paired t-test, at the end). No significant side-effects were recorded. CONCLUSIONS: The new whole-body cold treatment method may offer a safe option for self-treatment of pain at home but further study is needed to determine the clinical significance of the effect after longer use.
27783236 The effectiveness of new triple combination therapy using synthetic disease-modifying anti 2017 Jan The study aims to confirm the feasibility of new oral triple combination therapy using methotrexate (MTX), mizoribine (MZR), and tacrolimus (TAC) in patients with rheumatoid arthritis (RA) by in vitro and clinical analyses. Triple therapy with a combination of MTX, MZR, and TAC was used for an in vitro study with osteoclasts and a prospective clinical study in order to show the efficacy of these agents against refractory RA. In particular, low-dose TAC or MZR was added to treat 14 patients with RA that was resistant to MTX + MZR or MTX + TAC dual therapy. The combination of three pharmacological agents showed statistically significant differences to reduce differentiation induction and activity of osteoclasts compared with single and double agents. In clinical use, triple therapy showed a statistically significant difference in the improvement of Disease Activity Score-28-erythrocyte sedimentation rate and the Simple Disease Activity Index score at around 8 months. Additionally, the serum matrix metalloproteinase-3 level significantly decreased. No patients dropped out because of adverse effects. Based on this in vitro and prospective clinical study, oral triple therapy might be effective against refractory RA. Furthermore, this therapy might be safe and economical for clinical practice.
27926540 The novel interleukin-1 cytokine family members in inflammatory diseases. 2017 Mar PURPOSE OF REVIEW: This review provides an update on the new interleukin-1 (IL-1) cytokine family members in inflammatory diseases with focus on recent findings concerning the family members IL-36, IL-37, and IL-38 and their different expression patterns. RECENT FINDINGS: The IL-1 cytokines are known to be involved in many different inflammatory and autoimmune diseases. The latest IL-1 family members, IL-36, IL-37, and IL-38 have been shown to be differently regulated during course of disease. Studies of patients suffering from inflammatory diseases revealed that those cytokines are upregulated in the serum as well as in inflamed tissue. Both, epithelial cells and infiltrating peripheral mononuclear blood cells serve as source of the cytokines IL-36, IL-37, and IL-38 triggering different outcomes. These results could be confirmed in different mouse models and in-vitro and ex-vivo studies. SUMMARY: IL-36, IL-37, and IL-38 are involved in the pathogenesis of the inflammatory diseases psoriasis, rheumatoid arthritis, gout, systemic lupus erythematosus as well as Crohn's disease. Thereby IL-36 acts proinflammatory triggering further inflammatory mediators. In contrast, IL-37 and IL-38 are upregulated to counteract. Understanding the imbalance of the IL-1 family is crucial for future therapeutics.
28724396 Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: re 2017 Jul 19 BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone and cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in joint inflammation and bone destruction in arthritis. However, the specific mechanisms by which CXCL10 regulates the recruitment of inflammatory cells and the production of osteoclastogenic cytokines in RA progression are not fully understood. METHODS: Bone marrow-derived macrophages and CD4(+) T cells were isolated from wild-type (WT), Cxcl10 (-/-), and Cxcr3 (-/-) mice. CXCL10-induced migration was performed using a Boyden chamber, and CXCL10-stimulated production of osteoclastogenic cytokines was measured by quantitative real-time PCR and ELISA. Collagen antibody-induced arthritis (CAIA) was induced by administration of collagen type II antibodies and lipopolysaccharide to the mice. Clinical scores were analyzed and hind paws were collected for high-resolution micro-CT, and histomorphometry. Serum was used to assess bone turnover and levels of osteoclastogenic cytokines. RESULTS: CXCL10 increased the migration of inflammatory cells through C-X-C chemokine receptor 3 (CXCR3)-mediated, but not toll-like receptor 4 (TLR4)-mediated, ERK activation. Interestingly, both receptors CXCR3 and TLR4 were simultaneously required for CXCL10-stimulated production of osteoclastogenic cytokines in CD4(+) T cells. Furthermore, calcineurin-dependent NFATc1 activation was essential for CXCL10-induced RANKL expression. In vivo, F4/80(+) macrophages and CD4(+) T cells robustly infiltrated into synovium of WT mice with CAIA but were significantly reduced in both Cxcl10 (-/-) and Cxcr3 (-/-) mice. Serum concentrations of osteoclastogenic cytokines and bone destruction were also reduced in the knockout mice, leading to attenuated progression of arthritis. CONCLUSION: These findings highlight the importance of CXCL10 signaling in the pathogenesis of RA and provide previously unidentified details of the mechanisms by which CXCL10 promotes the development of arthritis.
28658716 Sustained secretion of anti-tumor necrosis factor α monoclonal antibody from ex vivo gene 2017 Aug BACKGROUND: Rheumatoid arthritis (RA) is a symmetric inflammatory polyarthritis associated with high concentrations of pro-inflammatory, cytokines including tumor necrosis factor (TNF)-α. Adalimumab is a monoclonal antibody (mAb) that binds TNF-α, and is widely used to treat RA. Despite its proven clinical efficacy, adalimumab and other therapeutic mAbs have disadvantages, including the requirement for repeated bolus injections and the appearance of treatment limiting anti-drug antibodies. To address these issues, we have developed an innovative ex vivo gene therapy approach, termed transduced autologous restorative gene therapy (TARGT), to produce and secrete adalimumab for the treatment of RA. METHODS: Helper-dependent (HD) adenovirus vector containing adalimumab light and heavy chain coding sequences was used to transduce microdermal tissues and cells of human and mouse origin ex vivo, rendering sustained secretion of active adalimumab. The genetically engineered tissues were subsequently implanted in a mouse model of RA. RESULTS: Transduced human microdermal tissues implanted in SCID mice demonstrated 49 days of secretion of active adalimumab in the blood, at levels of tens of microgram per milliliter. In addition, transduced autologous dermal cells were implanted in the RA mouse model and demonstrated statistically significant amelioration in RA symptoms compared to naïve cell implantation and were similar to recombinant adalimumab bolus injections. CONCLUSIONS: The results of the present study report microdermal tissues engineered to secrete active adalimumab as a proof of concept for sustained secretion of antibody from the novel ex vivo gene therapy TARGT platform. This technology may now be applied to a range of antibodies for the therapy of other diseases.
28121220 Functional results of hemi- and total shoulder arthroplasty according to diagnosis and pat 2017 Jun Background and purpose - There is a lack of information on any associations between the functional outcome and age and diagnosis in patients who have undergone shoulder arthroplasty. We therefore evaluated the functional outcome in "young" and "old" patients treated with either hemiarthroplasty (HA) or total shoulder arthroplasty (TSA) with diverse diagnoses. Patients and methods - The functional results of 496 primary shoulder arthroplasties were analyzed using the Constant score (age- and sex-adjusted) and subjective satisfaction. Patients ≤55 years of age at surgery were defined as "young. Diagnoses were primary osteoarthritis (n = 339), posttraumatic osteoarthritis (n = 78), cuff tear arthropathy (n = 36), avascular necrosis (n = 30), and rheumatoid arthritis (n = 13). Mean length of follow-up was 4 (2-14) years. Results - 70% of the TSA patients were very satisfied with the postoperative result, as compared to 39% after HA. The Constant score and patient satisfaction were similar in the "young" and "old" groups. Pain relief was better in the "old" group. The mean improvement in the Constant score after cuff tear arthropathy (22 points) was inferior to that for primary osteoarthritis (36 points), avascular necrosis (34 points), and rheumatoid arthritis (37 points). Inferior mean Constant scores were also seen for posttraumatic osteoarthritis (29 points) compared to primary osteoarthritis (36 points). 63% of patients with primary osteoarthritis were very satisfied, as compared to only 36% of the patients with posttraumatic osteoarthritis. Interpretation - Shoulder arthroplasty is successful in the medium term for different glenohumeral diseases, irrespective of patient age at surgery. However, the appropriate treatment method for cuff tear and posttraumatic conditions of the shoulder remains to be found, particularly in young patients.
28380667 Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis 2017 Jul OBJECTIVE: Antibodies to cyclic citrullinated peptides (anti-CCP) in rheumatoid arthritis (RA) can express the inherently autoreactive gene V(H) 4-34, detected using the rat monoclonal antibody 9G4. Patients with the polyarticular subtype of juvenile idiopathic arthritis (JIA) share some but not all of the features of adult patients with RA. This study was undertaken to compare serologic findings for rheumatoid factor (RF), anti-CCP, and 9G4-expressing anti-CCP in a large JIA cohort with a cohort of adult RA patients. METHODS: Serum from 88 patients with polyarticular JIA, 29 patients with enthesitis-related arthritis, 38 patients with extended oligoarthritis, 31 adolescent controls, 35 patients with RA, and 30 adult controls were tested for RF, for IgG, IgA, and IgM anti-CCP, and for 9G4-expressing anti-CCP by enzyme-linked immunosorbent assay. Total serum 9G4-positive IgM was also measured. RESULTS: Of 65 patients with RF-negative polyarticular JIA, 4 (6.2%) were IgG anti-CCP positive. Sera from 20 of 23 patients with RF-positive polyarticular JIA (87.0%), 24 of 35 patients with RA (68.6%), and 1 patient with extended oligoarthritis contained IgG anti-CCP. IgA and IgM anti-CCP levels were lower in the adolescent group (P < 0.01). Levels of 9G4-expressing anti-CCP were higher in patients with RF-positive polyarticular JIA than in those with RF-negative polyarticular JIA (P < 0.0001). Median levels of 9G4-expressing anti-CCP in patients with RF-positive polyarticular JIA and those with RA did not differ. Expression of 9G4 on serum total IgM was greater in patients with RF-positive polyarticular JIA than other adolescent groups (P < 0.01), but similar to adult RF-positive RA. CONCLUSION: In healthy individuals, 9G4-positive B cells comprise 5-10% of the peripheral blood pool but serum immunoglobulins utilizing V(H) 4-34 are disproportionately low. The idiotope recognized by 9G4 was detected on anti-CCP antibodies in >80% of patients with RF-positive polyarticular JIA. V(H) 4-34 usage by anti-CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes.
28288894 Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier 2017 Apr 28 Methotrexate (MTX), an anchor drug for rheumatoid arthritis (RA), has been suffered from refractoriness and high toxicity limiting effective dosage. To mitigate these challenges, the ability to selectively deliver MTX to arthritis tissue is a much sought-after modality for the treatment of RA. In this study, we prepared mineralized nanoparticles (MP-HANPs), composed of PEGylated hyaluronic acid (P-HA) as the hydrophilic shell, 5β-cholanic acid as the hydrophobic core, and calcium phosphate (CaP) as the pH-responsive mineral. Owing to the presence of CaP as the diffusion barrier, mineralized HANPs revealed the pH-responsiveness of release kinetics of MTX across neutral to acidic conditions. HANPs were internalized via receptor-mediated endocytosis in macrophages which involved molecular redundancy among major hyaladherins, including CD44, stabilin-2, and RHAMM. Following endocytosis, MP-HANPs loaded with doxorubicin revealed pH-dependent demineralization followed by dramatic acceleration of drug release into the cytosol compared to other HANPs. Furthermore, an in vivo study showed a significantly high paw-to-liver ratio of fluorescent intensity after systemic administration of MP-HANP-Cy5.5, indicating improved biodistribution of nanoparticles into arthritic paws in collagen-induced arthritis mice. Treatment with MTX-loaded MP-HANPs ameliorated inflammatory arthritis with remarkable safety at high dose of MTX. We highlight the distinct advantages of combining key benefits of biomineralization and PEGylation with HA-based nanoparticles for arthritis-selective targeting, thus suggesting MP-HANPs as a promising carrier of MTX for treatment of RA.
28860038 Functional complement activity is decisive for the development of chronic synovitis, osteo 2017 Oct Synovial inflammation plays a critical role in the symptoms and structural progression of arthritis which leads to irreversible damage of the adjacent cartilage and bone. Activation of complement system is strongly implicated as a factor in the pathogenesis of chronic synovitis in human rheumatoid arthritis (RA). In this study, we show that the depletion of functional complement activity at the time of the initiation of zymosan-induced arthritis, significantly reduced the expression of TGF-beta1/3, BMP2 and pSmad2 and decreased the number of Sudan Black B positive cells in the synovium. Also, the excessive synthesis of proteoglycans and glycosaminoglycans was diminished. The appearance of apoptotic and senescent cells among the adherent bone marrow cells cultivated in vitro was not observed in complement depleted mice. Therefore, the lack of functional complement prevented the development of chronic synovitis, osteophyte formation and the generation of pathologic senescent arthritic cells.
28608166 Abatacept: A Review in Rheumatoid Arthritis. 2017 Jul The biological DMARD (bDMARD) abatacept (Orencia(®)), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor. In phase III trials, beneficial effects on RA signs and symptoms, disease activity, structural damage progression and physical function were seen with intravenous (IV) or subcutaneous (SC) abatacept regimens, including abatacept plus methotrexate in methotrexate-naive patients with early RA and poor prognostic factors, and abatacept plus methotrexate or other cDMARDs in patients with inadequate response to methotrexate or TNF inhibitors. Benefits were generally maintained during longer-term follow-up. Absolute drug-free remission rates following withdrawal of all RA treatments were significantly higher with abatacept plus methotrexate than with methotrexate alone. Both IV and SC abatacept were generally well tolerated, with low rates of immunogenicity. Current evidence therefore suggests that abatacept is a useful treatment option for patients with RA.
27581002 Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid a 2017 Sep BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. MATERIAL AND METHODS: A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. RESULTS: This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093-1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130-1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096-1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. CONCLUSION: The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.
28987932 Ethyl pyruvate ameliorates inflammatory arthritis in mice. 2017 Nov OBJECTIVES: Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS: Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate-resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis-related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting. RESULTS: EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORγt. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP. CONCLUSIONS: EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis.
27992691 A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rh 2017 May OBJECTIVE: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). METHODS: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each second-line treatment was analyzed at randomization with the Breslow-Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30-44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]). RESULTS: Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab. CONCLUSION: In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.
28412710 Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in Patients w 2017 Jun OBJECTIVE: For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure. METHODS: We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ). RESULTS: Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments. CONCLUSION: In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.
27942977 Maintenance of efficacy and safety with subcutaneous golimumab in rheumatoid arthritis pat 2017 Apr The study was conducted to evaluate continued maintenance of the efficacy and safety of therapy by switching to subcutaneous golimumab (GLM-SC) in rheumatoid arthritis patients with low disease activity or remission who previously received a tumor necrosis factor (TNF) inhibitor. Thirty patients who had been treated with etanercept or infliximab were switched to GLM-SC in maintaining disease activity at a low level. The patients were divided into two groups through discussion with each patient, considering general condition and convenience: the low disease activity (LDA) group and the LDAq8w group, which included patients with low disease activity or remission who switched to 50 mg GLM therapy at 4- and 8-week intervals, respectively. The effects of the TNF inhibitors to GLM-SC switch were evaluated at 12, 24, and 52 weeks after switching. The mean DAS28-ESR and DAS-CRP values in the LDA groups (16 patients) and LDAq8w groups (14 patients) were maintained from baseline throughout the 52-week treatment period. DAS28-ESR remission (93.8 and 92.3%) rates were also maintained through week 52 from the baseline remission rate (75.0 and 78.6%) in the LDA and LDAq8w groups, respectively. Thus, both GLM-SC treatment regimens were effective in maintaining the clinical response achieved with LDA secondary to TNF inhibitors. No serious adverse events occurred, and the continuation rate at 52 weeks was 100% in both groups. Therapeutic efficacy is adequately maintained in most patients switching from TNF inhibitor to GLM-SC (50 mg/4-8 weeks). Patients receiving TNF inhibitor can seamlessly switch to GLM-SC without serious safety concerns.
28338619 Role and Function of A(2A) and A₃ Adenosine Receptors in Patients with Ankylosing Spondy 2017 Mar 24 Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A(2A) and A₃AR subtypes is often associated with a reduction of the inflammatory status. The aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A(2A) and A₃ARs in lymphocytes obtained from patients when compared with healthy subjects. A(2A) and A₃AR agonists inhibited nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation and reduced inflammatory cytokines release, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Moreover, A(2A) and A₃AR activation mediated a reduction of metalloproteinases (MMP)-1 and MMP-3. The effect of the agonists was abrogated by selective antagonists demonstrating the direct involvement of these receptor subtypes. Taken together, these data confirmed the involvement of ARs in chronic autoimmune rheumatic diseases highlighting the possibility to exploit A(2A) and A₃ARs as therapeutic targets, with the aim to limit the inflammatory responses usually associated with RA, AS and PsA.
28871953 [Detection and analysis of serum level of anti-Candida enolase IgG antibody in patients wi 2017 Aug Objective To detect IgG antibody against Candida enolase in the sera of patients with autoimmune diseases. Methods Using purified recombinant Candida enolase as the coating antigen, an ELISA was established for enolase IgG antibody detection and the reactive conditions were optimized. The enolase IgG antibody in the sera from patients with autoimmune diseases and healthy controls were detected by ELISA. The specificity of the positive sera was confirmed by Western blotting. Results The study collected 70 serum samples from the patients with autoimmune diseases and 44 from the healthy individuals. ELISA showed anti-Candida enolase IgG antibody in 19 cases of the autoimmune disease group and and 3 cases of the healthy control group, the positive rates of which were 27.14% (19/70) and 6.82% (3/44), respectively. In the autoimmune disease group, the positive rate of anti-Candida enolase IgG antibody in the systemic lupus erythematosus patients was 45.8% (11/24), significant higher than that in the rheumatoid arthritis patients (11.8%, 2/17). Western blotting validated the specificity of the positive sera. Conclusion The positive rate of anti-Candida enolase IgG antibody in patients with autoimmune disease is high, which would be an interference factor in the application of IgG antibody detection for the diagnosis of invasive candidiasis.