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ID PMID Title PublicationDate abstract
29257322 Human parvovirus B19 nonstructural protein NS1 activates NLRP3 inflammasome signaling in a 2018 Feb Dysregulation of inflammasomes serves a pathogenic role in autoinflammatory diseases (AIDs) and adult-onset Still's disease (AOSD) has been categorized as an AID. The present study investigated the expression of NLR family pyrin domain containing proteins (NLRPs) inflammasome in patients with AOSD, the effect of inflammasome inhibitors on NLRP3 signaling and whether human parvovirus B19‑associated antigens can activate NLRP3 in patients with AOSD. mRNA expression levels of NLRPs in peripheral blood mononuclear cells (PBMCs) from 34 patients with AOSD and 14 healthy individuals were determined using reverse transcription‑quantitative polymerase chain reaction. Protein expression of NLRP3 was evaluated by western blotting. Supernatant cytokine levels were measured by ELISA. Among the NLRPs investigated in the present study, NLRP3 transcripts were markedly elevated and expression of NLRP2, NLRP7 and NLRP12 was decreased in patients with AOSD compared with the controls. Treatment with NLRP3 inhibitors significantly reduced downstream NLRP3 signaling in PBMCs form patients with AOSD. B19‑nonstructural protein (NS)1 stimulation of PBMCs from patients with AOSD induced significant upregulation of transcript levels of NLRP3, caspase‑1 and interleukin (IL)‑1β compared with PBMCs from healthy controls. B19‑NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL‑1β and protein expression of NLRP3, caspase‑1, IL‑1β, and IL‑18 compared with healthy controls. Elevated expression of NLRP3 and its downstream inflammasome signaling components in patients with AOSD indicated a potential pathogenic role of B19‑NS1. Thus, B19‑NS1 may induce expression of IL‑1β and IL‑18 through activation of caspase‑1‑associated NLRP3‑inflammasome in AOSD.
28890641 Pharmaceutical Approval Update. 2017 Sep Sarilumab (Kevzara) for moderately to severely active rheumatoid arthritis; valbenazine (Ingrezza), the first approval for tardive dyskinesia; and cerliponase alpha (Brineura) for late infantile neuronal ceroid lipofuscinosis type-2 disease.
27590658 Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000-2 2017 Apr OBJECTIVES: It is not known if the incidences of autoimmune diseases are higher in individuals living with HIV infection or AIDS. Our study investigated the incidences of autoimmune diseases among people living with HIV/AIDS (PLWHA) in Taiwan during 2000-2012. METHODS: The Taiwan National Health Insurance Research Database was used to identify PLWHA. The incidence densities of systemic and organ-specific autoimmune diseases were calculated, and age-adjusted, sex-adjusted and period-adjusted standardised incidence rates (SIRs) were obtained by using two million people from the general population as controls. To examine the effects of highly active antiretroviral therapy (HAART) on the incidence of autoimmune diseases, the incidence densities and SIRs of autoimmune diseases were calculated after stratifying PLWHA by HAART status. RESULTS: Of the 20 444 PLWHA identified, the overall mean (SD) age was 30.1 (11.0) years; 67.2% of the subjects received HAART. As compared with the general population, SIRs were higher for incident Sjögren syndrome (SIR=1.64; 95% CI 1.24 to 2.13), psoriasis (SIR=2.05; 95% CI 1.67 to 2.48), systemic lupus erythematosus (SLE) (SIR=2.59; 95% CI 1.53 to 4.09), autoimmune haemolytic anaemia (SIR=35.06; 95% CI 23.1 to 51.02) and uveitis (SIR=2.50; 95% CI 2.05 to 3.02), but were lower for incident ankylosing spondyloarthritis (SIR=0.70; 95% CI 0.48 to 0.99). When the effect of HAART on incident autoimmune diseases was considered, PLWHA who received HAART had higher SIRs for psoriasis, autoimmune haemolytic anaemia and uveitis, but had lower risks of rheumatoid arthritis (RA) and ankylosing spondyloarthritis. In contrast, PLWHA who did not receive HAART had higher SIRs for Sjögren syndrome, psoriasis, RA, SLE, scleroderma, polymyositis, autoimmune haemolytic anaemia and Hashimoto's thyroiditis. CONCLUSIONS: PLWHA had higher risks of incident Sjögren syndrome, psoriasis, SLE, autoimmune haemolytic anaemia and uveitis.
28328098 Plasma exchange successfully treated macrophage activation syndrome in rheumatoid factor-p 2018 May Macrophage activation syndrome (MAS) is one of the serious complications associated with rheumatic diseases, especially systemic juvenile idiopathic arthritis (sJIA). Here we describe a 9-year-old girl with rheumatoid factor (RF)-positive polyarticular JIA, not sJIA, combined with pneumonia who was successfully treated by plasma exchange. She was diagnosed with RF-positive polyarticular JIA based on positive RF and multiple joint swelling and tenderness 3 years ago. She was admitted in our hospital with myalgia for 2 days and a high fever for half a day. Physical examination revealed relapsing joints symptoms and rough breathing sounds of lungs. The laboratory examination showed increased liver enzymes, elevated serum ferritin and procalcitonin (PCT), decreased percentage of nature killer (NK) cells and fibrinogen, and activated macrophage phagocytosing hematopoietic elements in bone marrow. The elevated PCT and chest computed tomography scan confirmed she also had pneumonia. Intravenous methylprednisolone and oral cyclosporine A followed by intravenous immunoglobulin were added on the basis of antibiotics therapy, but clinical symptoms and laboratory findings did not improve. Finally, we changed to plasma exchange once every other day for a total of three times. Within 1 week, the girl recovered from the MAS completely.
31643177 Etanercept. 2012 Etanercept is an antagonist of tumor necrosis factor alpha (TNFα) which has potent antiinflammatory activity and is used widely in severe forms of rheumatoid arthritis and psoriasis. Etanercept has been linked to rare instances of acute, clinically apparent liver injury.
28781508 American Society of Clinical Oncology And European League Against Rheumatism. 2017 Aug Notable American Society of Clinical Oncology sessions focused on prostate cancer, non-small-cell lung cancer, and hepatocellular carcinoma. Subjects at the European Congress of Rheumatology included rheumatoid arthritis and axial spondyloarthritis.
28687159 15 years of the histopathological synovitis score, further development and review: A diagn 2017 Aug The histopathological synovitis score evaluates the immunological and inflammatory changes of synovitis in a graduated manner generally customary for diagnostic histopathological scores. The score results from semiquantitative evaluation of the width of the synovial surface cell layer, the cell density of the stroma and the density of the inflammatory infiltration into 4 semiquantitative levels (normal 0, mild 1, moderate 2, severe 3). The addition of these values results in a final score of 0-9 out of 9. On the basis of this summation the condition is divided into low-grade synovitis and high-grade synovitis: A synovitis score of 1 to≤4 is called low-grade synovitis (arthrosis-associated/OA synovitis, posttraumatic synovitis, meniscopathy-associated synovitis and synovitis with haemochromatosis). A synovitis score of≥5 to 9 is called high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection/reactive arthritis and peripheral arthritis with Bechterew's disease). By means of the synovitis score it is therefore possible to distinguish between degenerative/posttraumatic diseases (low-grade synovitis) and inflammatory rheumatic diseases (high-grade synovitis) with a sensitivity of 61.7% and a specificity of 96.1%. The diagnostic accuracy according to ROC analysis (AUC: 0.8-0.9) is good. Since the first publication (2002) and an associated subsequent publication (2006), the synovitis score has nationally and internationally been accepted for histopathological assessment of the synovitis. In a PubMed data analysis (status: 14.02.2017), the following citation rates according to Cited by PubMed Central articles resulted for the two synovitis score publications: For DOI: 10.1078/0344-0338-5710261 there were 29 Cited by PubMed Central articles and for the second extended publication DOI:10.1111/j.1365-2559.2006.02508 there were 44 Cited by PubMed Central articles. Therefore a total of 73 PubMed citations are observed over a period of 15 years, which demonstrates an international acceptance of the score. This synovitis score provides for the first time a diagnostic, standardised and reproducible histopathological evaluation method enabling a contribution to the differential diagnosis of chronic inflammatory general joint diseases. This is particularly the case by incorporation into the joint pathology algorithm. To specify the synovitis score an immunohistochemical determination of various inflammation-relevant CD antigens is proposed to enable a risk stratification of high-grade synovitis (e.g.: progression risk and sensitivity for biologicals).
28849230 Tumor necrosis factor‑α‑induced protein‑8 like 2 regulates lipopolysaccharide‑ind 2017 Nov The endogenously activated rheumatoid arthritis (RA) synovial fibroblasts (RSFs) are likely to be the key to curing the disease. RSFs express Toll‑like receptors (TLRs) rendering them prone to activation by exogenous and endogenous TLR ligands, resulting in the production of chemokines and cytokines Germline deletion of tumor necrosis factor‑α‑induced protein‑8 like 2 (TIPE2, also known as TNFAIP8L2) results in fatal inflammation and hypersensitivity to TLR and T cell receptor stimulation. The present study demonstrates an inverse association between TIPE2 and cytokine gene expression in RSFs following lipopolysaccharide (LPS) stimulation. Enhanced TIPE2 expression decreased Ras‑related C3 botulinum toxin substrate (Rac) activation and interferon regulatory factor 3 phosphorylation, and phosphoinositide 3‑kinase and Rac inhibition significantly diminished LPS‑induced cytokine gene expression in RSFs. In conclusion, the findings of the present study demonstrate that TIPE2 serves a negative role in activating the Rac signaling pathway and in the initiation of the immune response by decreasing the activity of proinflammatory cytokines. These results may be useful in designing novel strategies for the prevention and treatment of RA.
28957555 Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen- 2017 Oct 1 OBJECTIVE: miRNAs are small, signal-strand, non-coding RNAs that function in post-transcriptional regulation. We analysed the in vivo effect of miR-106b (miR-106b-5p) on inflammatory bone loss in CIA mice. METHODS: CIA mice are developed by injecting DAB/1 mice with bovine type II collagen containing Freund's adjuvant and then the in vivo effect of miR-106b is examined. On day 22, mice were given lentiviral negative control, lentiviral-mediated miR-106b mimics or lentiviral-mediated miR-106b inhibitor via orbital injection on a weekly basis. Morphological changes in the ankle joints were assessed via micro-CT and histopathology and cytokine expression levels were examined via immunohistochemical staining, ELISA or flow cytometric analysis. miR-106b and osteoclastic-related gene expression was evaluated via quantitative real-time PCR. RESULTS: CIA mice were found to have increased miR-106b expression and CIA-associated bone loss and inflammatory infiltration. miR-106b inhibitor treatment markedly decreased arthritis incidence and attenuated bone destruction and histological severity compared with the control group. Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice. miR-106b inhibition also significantly decreased inflammatory mediator production in joint sections and reduced serum pro-inflammatory cytokine levels when compared with the control group. Additionally, miR-106b inhibition decreased tartrate-resistant acid phosphatase-positive cell numbers and suppressed murine bone marrow macrophage differentiation. CONCLUSION: These findings indicate that miR-106b inhibition can ameliorate CIA-associated inflammation and bone destruction and thus may serve as a potential therapeutic for human RA treatment.
28986307 Interleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondr 2018 Jan The acute-phase proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1β and TNF-α in acid-induced apoptosis of chondrocytes remain unclear. Rat adjuvant arthritis and primary articular chondrocytes were used as in vivo and in vitro model systems, respectively. ASIC1a expression in articular cartilage was increased and highly colocalized with nuclear factor (NF)-κB expression in vivo. IL-1β and TNF-α could upregulate ASIC1a expression. These cytokines activated mitogen-activated protein kinase and NF-κB pathways in chondrocytes, while the respective inhibitors of these signaling pathways could partially reverse the ASIC1a upregulation induced by IL-1β and TNF-α. Dual luciferase and gel-shift assays and chromatin immunoprecipitation-polymerase chain reaction demonstrated that IL-1β and TNF-α enhanced ASIC1a promoter activity in chondrocytes by increasing NF-κB DNA-binding activities, which was in turn prevented by the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate. IL-1β and TNF-α also decreased cell viability but enhanced LDH release, intracellular Ca(2+) concentration elevation, loss of mitochondrial membrane potential, cleaved PARP and cleaved caspase-3/9 expression, and apoptosis in acid-stimulated chondrocytes, which effects could be abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1), ASIC1a-short hairpin RNA or calcium chelating agent BAPTA-AM. These results indicate that IL-1β and TNF-α can augment acidosis-induced cytotoxicity through NF-κB-dependent up-regulation of ASIC1a channel expression in primary articular chondrocytes.
28524619 Use of complementary and alternative medicines is associated with delay to initiation of d 2017 May OBJECTIVES: To study the predictors of complementary and alternative medicine (CAM) use in patients with early inflammatory arthritis (EIA), and its impact on delay to initiation of disease-modifying anti-rheumatic drugs (DMARD). METHODS: Data were collected prospectively from EIA patients aged ≥ 21 years. Current or prior CAM use was ascertained by face-to-face interview. Predictors of CAM use and its effect on time to DMARD initiation were determined by multivariate logistic regression and Cox proportional hazards, respectively. RESULTS: One hundred and eighty patients (70.6% female, 58.3% Chinese), of median (interquartile range [IQR]) age 51.1 (40.9-59.8) years and symptom duration 16.6 (9.2-26.6) weeks were included: 83.9% had rheumatoid arthritis, 57% were seropositive. Median (IQR) Disease Activity Score in 28-joints (DAS28) was 4.3 (2.8-5.7), modified Health Assessment Questionnaire (mHAQ) was 0.38 (0.0-0.88) and 41.3% were CAM users. Chinese race (odds ratio [OR] 5.76 [95%CI 2.53-13.1]), being non-English speaking (OR 2.68 [95% CI 1.18-6.09]), smoking (OR 3.35 [95% CI 1.23-9.15] and high DAS28 (OR 2.73 [95% CI 1.05-7.09] were independent predictors of CAM use. CAM users initiated DMARD later (median [IQR] 21.5 [13.1-30.4] vs. 15.6 [9.4-22.7] weeks in non-users, P = 0.005). CAM use and higher DAS28 were associated with a longer delay to DMARD initiation (hazard ratio [HR] 0.69, 95% CI 0.50-0.95 and 0.63, 95% CI 0.43-0.91, respectively) while higher mHAQ was associated with a shorter delay (HR 1.59, 95% CI 1.08-2.34) and race, education level, being non-English speaking, smoking and seropositivity were not associated. CONCLUSIONS: Healthcare professionals should be aware of the unique challenges in treating patients with EIA in Asia. Healthcare beliefs regarding CAM may need to be addressed to reduce treatment delay.
28759646 Local cryotherapy improves adjuvant-induced arthritis through down-regulation of IL-6 / IL 2017 OBJECTIVES: Local cryotherapy is widely and empirically used in the adjuvant setting in rheumatoid arthritis treatment, however its own therapeutic and anti-inflammatory effects are poorly characterized. We aimed to evaluate the effects of local cryotherapy on local and systemic inflammation in Adjuvant-induced arthritis, a murine model of rheumatoid arthritis. METHODS: The effects of mild hypothermia (30°C for 2 hours) on cytokine protein levels (Multiplex/ELISA) were evaluated in vitro in cultured rat adjuvant-induced arthritis patellae. In vivo, local cryotherapy was applied twice a day for 14 days in arthritic rats (ice: n = 10, cold gas: n = 9, non-treated: n = 10). At day 24 after the induction of arthritis, cytokine expression levels were measured in grinded hind paws (Q-RT-PCR) and in the plasma (Multiplex/ELISA). RESULTS: In vitro, punctual mild hypothermia down-regulated IL-6 protein expression. In vivo, ice showed a better efficacy profile on the arthritis score and joint swelling and was better tolerated, while cold gas induced a biphasic response profile with initial, transient arthritis worsening. Local cryotherapy also exerted local and systemic anti-inflammatory effects, both at the gene and the protein levels: IL-6, IL-17A and IL-1β gene expression levels were significantly down-regulated in hind paws. Both techniques decreased plasma IL-17A while ice decreased plasma IL-6 protein levels. By contrast, we observed no effect on local/systemic TNF-α pathway. CONCLUSIONS: We demonstrated for the first time that sub-chronically applied local cryotherapy (ice and cold gas) is an effective and well-tolerated treatment in adjuvant-induced arthritis. Furthermore, we provided novel insights into the cytokine pathways involved in Local cryotherapy's local and systemic anti-inflammatory effects, which were mainly IL-6/IL-17A-driven and TNF-α independent in this model.
29387051 Elevated Serum Lysophosphatidylcholine in Patients with Systemic Lupus Erythematosus Impai 2017 OBJECTIVES: Impaired clearance of dying and dead cells by professional and amateur phagocytes plays a crucial role in the etiology of systemic lupus erythematosus (SLE). While dying, cells expose and release a plethora of eat-me and find-me signals to ensure their timely removal before entering the dangerous stage of secondary necrosis. A well-described chemoattractant for macrophages is dying cell-derived lysophosphatidylcholine (LPC). However, its implications for and/or its association with SLE disease, so far, have not been examined. In the present study, we analyzed the LPC serum concentrations of patients with SLE and rheumatoid arthritis (RA). Subsequently, we examined if and to which extent the measured serum concentrations of LPC and an LPC-rich environment can impact the phagocytosis of necrotic cells. METHODS: Sera from patients with SLE, RA, and normal healthy donors (NHD) were characterized for several parameters, including LPC concentrations. Phagocytosis of dead cells by human macrophages in the presence of SLE and NHD sera was quantified. Additionally, the impact of exogenously added, purified LPC on phagocytosis was analyzed. RESULTS: Patients with SLE had significantly increased LPC serum levels, and high serum LPC of SLE patients correlated significantly with impaired phagocytosis of dead cells in the presence of heat-inactivated serum. Phagocytosis in the presence of sera from NHD showed no correlation to LPC levels, but exogenous addition of purified LPC in the range as measured in SLE patients' sera led to a concentration-dependent decrease. CONCLUSION: Our data show that high levels of LPC as observed in the sera of SLE patients have a negative impact on the clearance of dead cells by macrophages. Chemoattraction requires a concentration gradient. The higher the LPC concentration surrounding a dying or dead cell, the smaller the achievable gradient upon LPC release will be. Thus, it is feasible to assume that elevated LPC levels can interfere with the build-up of a local LPC gradient during cell death, and hence might play a role in the establishment and/or perpetuation of SLE disease.
28511921 Myeloperoxidase: A new player in autoimmunity. 2017 Jul Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H(2)O(2) to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby MPO is thought to contribute to disease pathogenesis include tuning of adaptive immune responses and/or the induction of vascular permeability.
28255897 bDMARD Dose Reduction in Rheumatoid Arthritis: A Narrative Review with Systematic Literatu 2017 Jun INTRODUCTION: Although bDMARDs are effective in the treatment of RA, they are associated with dose-dependent side effects, patient burden, and high costs. Recently, many studies have investigated the possibility of discontinuing or tapering bDMARDs when patients have reached their treatment goal. The aim of this review is to provide a narrative overview of the existing evidence on bDMARD dose reduction and to provide answers to specific dose-reduction-related questions that are of interest to clinicians. METHODS: We systematically searched for relevant studies in four scientific databases. Furthermore, we screened the references of reviews and relevant studies. RESULTS: Our searches resulted in 45 original studies of bDMARD dose reduction in RA patients (15 RCTs and 30 observational studies). Current evidence shows that bDMARD dose reduction can be considered in all RA patients who achieve stable (e.g., ≥6 months) low disease activity or remission. The best strategies seem to be disease-activity-guided dose optimization and fixed dose reduction, since direct bDMARD discontinuation (without restarting) results in a high flare rate, worse physical functioning, and more joint damage. When tapering the bDMARD treatment of a patient, disease activity should be monitored closely, and if a flare occurs, the dose should be increased to the lowest effective dose. Current evidence shows that restarting bDMARD treatment is effective and safe. Unfortunately, no clear predictors of successful dose reduction have been identified so far. CONCLUSION: The current evidence and rising healthcare costs urge that dose reduction should be considered for eligible patients. However, the decision to start dose reduction should be made in shared decision-making. Future research should focus not only on a better understanding of the effects of dose reduction on clinical outcomes but also on the perspectives of patients and physicians as well as the implementation of this new treatment principle.
28233185 Clinical Development of Histamine H(4) Receptor Antagonists. 2017 The discovery of the histamine H(4) receptor (H(4)R) provided a new avenue for the exploration of the physiological role of histamine, as well as providing a new drug target for the development of novel antihistamines. The first step in this process was the identification of selective antagonists to help unravel the pharmacology of the H(4)R relative to other histamine receptors. The discovery of the selective H(4)R antagonist JNJ 7777120 was vital for showing a role for the H(4)R in inflammation and pruritus. While this compound has been very successful as a tool for understanding the function of the receptor, it has drawbacks, including a short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies. Further research let to the discovery of JNJ 39758979, which, similar to JNJ 7777120, was a potent and selective H(4)R antagonist and showed anti-inflammatory and anti-pruritic activity preclinically. JNJ 39758979 advanced into human clinical studies and showed efficacy in reducing experimental pruritus and in patients with atopic dermatitis. However, development of this compound was terminated due to the occurrence of drug-induced agranulocytosis. This was overcome by developing another H(4)R antagonist with a different chemical structure, toreforant, that does not appear to have this side effect. Toreforant has been tested in clinical studies in patients with rheumatoid arthritis, asthma, or psoriasis. In conclusions there have been many H(4)R antagonists reported in the literature, but only a few have been studied in humans underscoring the difficulty in finding ligands with all of the properties necessary for testing in the clinic. Nevertheless, the clinical data to date suggests that H(4)R antagonists can be beneficial in treating atopic dermatitis and pruritus.
28186427 Meta-Analysis of Risk Association Between Interleukin-17A and F Gene Polymorphisms and Inf 2017 Apr This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease. PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct were searched, and odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the strength of the association. A total of 25 studies comprising 7,474 cases and 10,628 controls were included. Significant associations were found between inflammatory diseases and IL-17A rs2275913 A versus G allele (OR = 1.197, P = 0.033) and the GA versus GG genotype in the codominant model (OR = 1.406, P = 0.036). Our findings suggested that individuals who carry the rs2275913 A allele or GA genotype have a 20% or 41%-increased risk of inflammatory diseases compared with subjects with the G allele or GG genotype, respectively. With respect to IL-17F rs763780, the C versus T allele (OR = 1.94; P = 0.040), the TC versus TT (OR = 1.39; P = 0.041), the CC versus TT (OR = 2.71; P = 0.003), as well as the TC + CC versus TT genotype (OR = 1.83; P = 0.032) were risk factors for RA. In summary, our pooled analysis indicated that the IL-17A (rs2275913) and IL17F (rs763780 T/C) increased the RA risk.
29042750 Current perspective on rituximab in rheumatic diseases. 2017 The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.
28975392 Second-line treatment persistence and costs among patients with immune-mediated rheumatic 2017 Dec The objective of this study was to describe treatment persistence with second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with immune-mediated rheumatic diseases (IMRDs) in Sweden, and the impact of non-persistence on healthcare costs. This retrospective observational study was based on Swedish national health register data. Adults were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM). Persistence was estimated over 3 years for propensity score-matched (PSM) cohorts using non-parametric survival analysis. Unadjusted comparisons of costs comprised specialized outpatient care, inpatient care, and medication. In total, N = 845 patients were identified and three PSM cohorts were generated (GLM vs. ADA, ETA, and CZP, respectively). GLM exhibited higher persistence than ADA over the study period (p = 0.040), and numerically higher persistence than ETA and CZP for 36 and 30 months, respectively. Persistent and non-persistent patients had similar mean total cost at 12 month pre-treatment ($5185 vs. $5064, p = 0.750). During the 12 month post-treatment initiation, persistent patients had lower mean total costs ($4377 vs. $6605), corresponding to a cost difference of $2228 (p < 0.001). In second-line treatment with SC-TNFis for IMRDs in Sweden, GLM exhibited significantly higher persistence than ADA over the course of the study. Similarly, GLM showed numerically higher persistence than ETA and CZP, which is concurrent with results observed in first-line SC-TNFi treatment. Considering the lower healthcare costs for persistent patients, the choice of second-line SC-TNFi among eligible patients may merit careful consideration given its impact on patients and payers.
29270179 Aging, Obesity, and Inflammatory Age-Related Diseases. 2017 The increase in the prevalence of obesity represents a worldwide phenomenon in all age groups and is pathologically and genetically correlated with several metabolic and cardiovascular diseases, representing the most frequent age-related diseases. Obesity superimposed on aging drastically increases chronic low-grade inflammation (inflammaging), which is an important link between obesity, insulin resistance, and age-associated diseases. Immune cells of both the innate and the adaptive immune systems infiltrate the adipose tissue (AT) and during obesity induce inflammatory responses associated with metabolic switches and changes in phenotypes and function of immune cell subsets. Obesity poses new health problems especially when it occurs in the context of other diseases, many of them frequently affect elderly subjects. An emerging problem is the decreased proportion of patients with obesity achieving clinical response to therapy. In this review, we will discuss the reciprocal influences of immune cell and AT inflammation in aging and age-associated diseases and the complex relationship of nutrient and energy-sensing homeostatic checkpoints, which contribute to shape the phenotype of the AT. We will specifically examine type-2 diabetes, rheumatoid arthritis, osteoarthritis, cognitive impairment, and dementia, where obesity plays a significant role, also in shaping some clinical aspects.