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ID PMID Title PublicationDate abstract
26354427 Entheseal involvement in systemic disorders. 2015 Dec The objective of this study is to review the data on entheseal involvement in systemic disorders. A Pubmed search utilizing the indexing terms "enthesis" and "enthesitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. A number of cadaver-based studies, as well as studies using ultrasonography and magnetic resonance imaging, have detailed new distinct aspects of enthesis physiology and pathology in a variety of rheumatic and non-rheumatic systemic disorders. Major progress has been done in characterization of separate components of the enthesis organ, imaging of entheses, elaboration of the role and features of entheseal disease in spondyloarthropathies, juvenile idiopathic arthritis, osteoarthritis, familial Mediterranean fever, hyperuricemia, and other systemic conditions. The knowledge acquired and summarized herein shows that entheses can be affected in various ways in variety of medical disorders with different pathogenesis. Better understanding of the risk factors, mechanisms and natural history of enthesopathies is warranted. The current progress in the understanding of entheseal involvement in systemic disorders represents just the first step in resolving the entheses-related enigmas.
25962765 TNF-related apoptosis-inducing ligand and cardiovascular disease in rheumatoid arthritis. 2015 Jul OBJECTIVES: We examined the association of TNF-related apoptosis-inducing ligand (TRAIL) concentrations with cardiovascular disease (CVD) in rheumatoid arthritis (RA) and, since osteoprotegerin (OPG) can act as a decoy receptor for TRAIL, whether TRAIL concentrations impact on the OPG level-atherosclerotic CVD relation that was recently documented in the present cohort. METHODS: TRAIL concentrations were assessed by ELISA in 151 RA patients of which 75 (49.7%) had CVD comprising ischaemic heart disease (n=27), cerebrovascular accident (n=26), peripheral artery disease (n=9) or/and heart failure (HF) (n=27), and 62 controls. RESULTS: Mean RA duration was 12 years. In RA patients, C-reactive protein (CRP) levels and cholesterol-HDL cholesterol ratio related to TRAIL concentrations [partial R=-0.222 (p=0.006) and 0.174 (p=0.04), respectively]. TRAIL concentrations were smaller in RA patients compared to controls (median (interquartile range) = 80.2 (60.9-120.4) versus 130.4 (89.4-167.7) pg/ml, p<0.0001)). TRAIL levels were larger in RA patients with compared to those without HF (105.5 (66.5-143.4) versus 79.9 (57.8-110.6), p=0.02); this difference was independent of demographic characteristics and traditional cardiovascular risk factors (p=0.04) but not CRP concentrations (p=0.1). TRAIL levels were consistently unrelated to atherosclerotic CVD. Our previously reported OPG-atherosclerotic CVD relation in RA survived adjustment for TRAIL concentrations in a mixed regression model (p=0.04). CONCLUSIONS: TRAIL concentrations are markedly reduced and associated with HF in established RA, this relationship being explained by CRP levels. OPG may directly enhance CVD risk in RA.
25948694 Impact of Diabetes on Outcome of Total Ankle Replacement. 2015 Oct BACKGROUND: As the incidence of diabetes mellitus (DM) grows, managing patients with diabetes and concomitant ankle arthritis poses a challenging clinical dilemma. While diabetes is known to be a risk factor for complications relating to open reduction and internal fixation of ankle fractures, it is unclear if DM is a risk factor for negative outcomes after total ankle replacement (TAR). METHODS: We retrospectively identified a consecutive series of 813 primary TARs performed between 2002 and November 2013 that had a minimum follow-up of 1 year. Within that larger group, we identified 50 patients with DM and used a control group without DM for comparison (n = 55). Clinical outcomes including wound issues, infection rates, complications, and failure rates were then compared. Functional outcomes, including American Orthopaedic Foot & Ankle Society hindfoot score, Short Form-36 (SF-36), Short Musculoskeletal Function Assessment, Foot and Ankle Disability Index, and visual analog scale, were also compared. Median patient follow-up was 2.3 years in the DM group and 3.1 years in the control group (P = .239). RESULTS: The body mass index, age, preoperative American Society of Anesthesiologists (ASA) grading, and smoking history in the DM were significantly higher than in the control group. While 5 patients (10%) in the DM group had secondary operations related to the TAR, no patients had a superficial or deep infection. Eight patients (14.5%) in the control group had secondary operations, including 1 patient who needed a flap. There was no statistical differences in secondary operations (P = .562), revisions (P = .604), or failure rates (P = .345). For both the diabetes and control groups, all functional outcome scores except SF-36 General Health significantly improved at 1 year postoperatively; these improvements were maintained at most recent follow-up. There was no statistically significant difference between the groups regarding functional outcomes except that at 1 year, the magnitude of improvement in SF-36 General Heath was significantly better in the control group. CONCLUSIONS: Total ankle arthroplasty appears to be an effective and safe means for providing pain relief and improving function in patients with diabetes and ankle arthritis. While patients with DM were heavier and had worse ASA preoperative grades, they did not have a significantly different complication or infection rate. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
25943573 Neuroendocrine and viral correlates of premature immunosenescence. 2015 Sep Aging continuously remodels the immune system, a process known as immunosenescence. Here, we review evidence of premature immunosenescence in younger individuals under conditions of chronic psychological stress, chronic inflammation, or exposure to certain persistent viral infections. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic-pituitary-adrenal axis and increased cortisol levels. Chronic stress is associated with thymic involution, blunted T cell proliferation, increased serum proinflammatory markers, and shorter telomere lengths. Human cytomegalovirus (CMV) infection has been implicated in accelerating immunosenescence by shrinking the T cell receptor repertoire and causing clonal expansion of senescent CD8(+) CD28(-) T cells with a proinflammatory profile. These factors increase inflammation associated with aging, or "inflammaging," particularly as it relates to etiology of several age-related diseases and increased mortality. Patients with rheumatoid arthritis have been shown to have several signatures of premature immunosenescence, including expansion of senescent T cells associated with cognitive impairment. We end by speculating that bipolar disorder can be considered as a model of accelerated aging because it has been associated with shortened telomeres, higher CMV IgG titers, and expansion of senescent and regulatory T cells.
25656802 Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T 2015 May Sinomenine (SIN) has long been used as a therapeutic agent of rheumatoid arthritis (RA) in China. However, the discrepancy between low oral bioavailability and higher minimal effective concentration made its action mode mysterious. The present study aimed to gain insight into the mechanisms by which SIN suppressed collagen-induced arthritis (CIA) in rats in view of Th17 and regulatory T (Treg) cell balance. SIN was orally administered, and the clinical symptoms of CIA rats were monitored; inflammatory cytokines levels in serum were measured by ELISA; pharmacokinetic studies were performed in normal and CIA rats; Th17 and Treg cell frequencies were analyzed by flow cytometry. The data showed that SIN treatment resulted in a dramatic decrease of arthritis scores and paw volume of CIA rats, which was accompanied by down-regulation of IL-17A and up-regulation of IL-10 in rat serum. The frequency of Treg cells was increased and the frequency of Th17 cells was decreased in the gut lymphoid tissues of SIN-treated rats. Immunohistochemistry assay demonstrated that more α4β7-positive cells were detained in joint tissues after SIN treatment. Moreover, the anti-arthritis efficacy of SIN disappeared when it was given by intraperitoneal injection, further confirming the action of SIN was gut-dependent. In conclusion, SIN exerts anti-RA action probably through modulating the frequencies of Treg cells and Th17 cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from gut to joint.
25306496 Shoulder arthroplasty in patients younger than 50 years: minimum 20-year follow-up. 2015 May BACKGROUND: Little information is available on the long-term outcome of shoulder arthroplasty in young patients. The purpose of this study was to report the results, complications, and revision rate of total shoulder arthroplasties (TSAs) in patients younger than 50 years at a minimum 20-year follow-up. MATERIALS AND METHODS: Between 1976 and 1985, a single surgeon performed 78 Neer hemiarthroplasties (HAs) and 36 Neer TSAs in patients < 50 years. Fifty-six HAs and 19 TSAs with a minimum 20-year follow-up, or follow-up until reoperation, were analyzed for clinical, radiographic and survivorship outcomes. RESULTS: Both HA and TSA showed significant improvements in pain scores (P < .001), abduction (P < .01), and external rotation (P = .02). Eighty-one percent of shoulders were rated much better or better than preoperatively. Modified Neer ratings were similar between groups (P = .41). Unsatisfactory ratings in HA were due to reoperations in 25 (glenoid arthrosis in 16) and limited motion, pain, or dissatisfaction in 11. Unsatisfactory ratings in TSA were due to reoperations in 6 (component loosening in 4) and limited motion in 5. Estimated 20-year survival was 75.6% (confidence interval, 65.9-86.5) for HAs and 83.2% (confidence interval, 70.5-97.8) for TSAs. DISCUSSION: At long-term follow-up, both HA and TSA continue to provide lasting pain relief and improved range of motion. However, there are a large number of unsatisfactory Neer ratings. Whereas both groups have survivorship in excess of 75% at 20 years, surgeons should remain cautious in performing shoulder arthroplasty in the young patient.
26403779 The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis. 2015 Sep 25 Periodontitis is an infective process that ultimately leads to destruction of the soft and hard tissues that support the teeth (the periodontium). Periodontitis has been proposed as a candidate risk factor for development of the autoimmune disease rheumatoid arthritis (RA). Porphyromonas gingivalis, a major periodontal pathogen, is the only known prokaryote expressing a peptidyl arginine deiminase (PAD) enzyme necessary for protein citrullination. Antibodies to citrullinated proteins (anti-citrullinated protein antibodies, ACPA) are highly specific for RA and precede disease onset. Objective of this study was to assess P. gingivalis PAD (PPAD) gene expression and citrullination patterns in representative samples of P. gingivalis clinical isolates derived from periodontitis patients with and without RA and in related microbes of the Porphyromonas genus. Our findings indicate that PPAD is omnipresent in P. gingivalis, but absent in related species. No significant differences were found in the composition and expression of the PPAD gene of P. gingivalis regardless of the presence of RA or periodontal disease phenotypes. From this study it can be concluded that if P. gingivalis plays a role in RA, it is unlikely to originate from a variation in PPAD gene expression.
27109640 Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome. 2016 Jul Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.
26773107 Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-α Inhibitors: Re 2016 Mar OBJECTIVE: Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF. METHODS: Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available. RESULTS: Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88-6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43-6.9, p = 0.004) were independent predictors of TB development. CONCLUSION: Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.
26671522 Characterization of synovial mast cells in knee osteoarthritis: association with clinical 2016 Apr OBJECTIVE: To investigate the presence of mast cells in the osteoarthritic (OA) synovium and their association with clinical parameters in comparison with rheumatoid arthritis (RA) samples. METHOD: Synovial tissues of 56 symptomatic OA and 49 RA patients were obtained. Two to three paraffin slides were used to quantify inflammation using haematoxylin and eosin (H&E) staining (synovitis score 0-9), and numbers of mast cells (per 10 high-power fields) using double immunofluorescence for CD117 and tryptase. Average scores per patient were used for analysis. Knee radiographs of OA patients were scored according to the Kellgren and Lawrence (KL) system and pain was determined in OA patients at baseline by visual analogue scale (VAS). RESULTS: Median (range) of mast cells was significantly higher in OA samples 45 (1-168) compared to RA samples 4 (1-47) (P-value < 0.001), despite a lower median (range) synovitis score in OA (2.5 (0-6.0)) compared to 4.6 (0-8.0) in RA samples. The synovitis score was significantly correlated with the number of mast cells (in OA Spearman's rho (P-value) 0.3 (0.023) and RA 0.5 (P-value < 0.001)). Interestingly, we observed a trend towards an association between the number of mast cells and an increased KL-grade (P-value 0.05) in OA patients, independently of synovitis. No associations were found with self-reported pain. CONCLUSION: Prevalence of mast cells in OA synovial tissue is relatively high and associates with structural damage in OA patients, suggesting a role of mast cells in this disease.
27847407 Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-L 2016 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factor β-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.
26473751 VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate 2016 Jan OBJECTIVE: To assess the efficacy and safety of decernotinib (VX-509), an oral selective inhibitor of JAK-3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. METHODS: In this 24-week, double-blind, randomized phase IIb study, 358 patients with active RA received either placebo (n = 71) or VX-509 at dosages of 100 mg/day (n = 71), 150 mg/day (n = 72), 200 mg/day (n = 72), or 100 mg twice daily (n = 72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). RESULTS: At week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX-509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P < 0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28-CRP was significantly greater in each VX-509 group compared with the placebo group (P < 0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28-CRP. The most common adverse event in the VX-509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed. CONCLUSION: VX-509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid levels.
26065000 Osteoprotegerin Polymorphisms in a Mexican Population with Rheumatoid Arthritis and Genera 2015 Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50 ± 12 with disease duration of 12 ± 8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA.
27865758 Bone Morphogenetic Protein 2 and Transforming Growth Factor β1 Inhibit the Expression of 2017 Jan IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-β family, TGF-β1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34, TGF-β1, and BMP-2 productions were measured in patient synovial fluids by enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells. Pharmacologic inhibitions were used to determine the involvement of activin receptor-like kinase 1 (ALK1) and ALK5 downstream TGF-β1 and BMP-2. IL-34, TGF-β1, and BMP-2 were expressed in synovial fluids from RA patients. We found a significant correlation between IL-34 and TGF-β1 expressions. Levels of both IL-34 and TGF-β1 were thus correlated with the total leukocyte counts in the synovial fluids. TGF-β1 and BMP-2 decreased IL-34 expression in the synovial fibroblasts or in murine mesenchymal stem cells in a dose- and time-dependent manner through ALK5 and ALK1 pathways, respectively. In addition, TGF-β1 and BMP-2 antagonized tumor necrosis factor α-induced IL-34 gene expression. This work identifies TGF-β1 and BMP-2 as potent inhibitors of IL-34 expression in RA synovial fibroblasts. These cytokines, as upstream inhibitors of IL-34, may thus contribute to antagonize inflammation and bone erosions in RA.
27931536 Advances in atopic dermatitis in 2015. 2016 Dec This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector T(H)2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, T(H)17 dominance in Asians with AD). As diagnostics, noninvasive examinations of the transepidermal water loss of neonates, the density of epidermal Staphylococcus species, and the gut flora might prognosticate the onset of AD. As for therapy, various methods are proposed, including conventional (petrolatum and UV) and molecule-oriented regimens targeting Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, sirtuin 1, or aryl hydrocarbon receptor.
26525227 In-depth characterization of CD24(high)CD38(high) transitional human B cells reveals diff 2016 May BACKGROUND: CD24(high)CD38(high) transitional B cells represent cells at a key stage in their developmental pathway. In addition, these B cells have been widely ascribed regulatory functions and involvement in the control of chronic inflammatory diseases. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial. OBJECTIVE: In this study we wanted to explore the regulatory properties of CD24(high)CD38(high) human B cells. METHODS: We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24(high)CD38(high) B cells can be distinguished into multiple subsets with different regulatory functions. RESULTS: For the first time, the study reveals that human transitional B cells encompass not only transitional type 1 and type 2 B cells, as previously suggested, but also distinct anergic type 3 B cells, as well as IL-10-producing CD27(+) transitional B cells. Interestingly, the latter 2 subsets differentially regulate CD4(+) T-cell proliferation and polarization toward TH1 effector cells. Additional analyses reveal that the percentage of type 3 B cells is reduced and the frequency of CD27(+) transitional B cells is increased in patients with autoimmune diseases compared with those in matched healthy subjects. CONCLUSION: This study provides evidence for the existence of different transitional B-cell subsets, each displaying unique phenotypic and regulatory functional profiles. Furthermore, the study indicates that altered distribution of transitional B-cell subsets highlights different regulatory defects in patients with different autoimmune diseases.
27183580 Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxy 2016 Jun 15 Piperlongumine (PLM) is a natural product from the plant Piper longum that inhibits platelet aggregation, atherosclerosis plaque formation, and tumor cell growth. It has potential value in immunomodulation and the management of autoimmune diseases. In this study, we investigated the role of PLM in regulating the differentiation and maturation of dendritic cells (DCs), a critical regulator of immune tolerance, and evaluated its clinical effects in a rheumatoid arthritis mouse model. We found that PLM treatment reduced LPS-induced murine bone marrow-derived DC maturation, characterized by reduced expression of CD80/86, secretion of MCP-1, IL-12p70, IL-6, TNFα, IFN-γ, and IL-23, and reduced alloproliferation of T cells; however, PLM does not affect cell differentiation. Furthermore, PLM reduced intracellular reactive oxygen species (ROS) production by DCs and inhibited the activation of p38, JNK, NF-κB, and PI3K/Akt signaling pathways. Conversely, PLM increased the expression of GSTP1 and carbonyl reductase 1, two enzymes that counteract ROS effects. ROS inhibition by exogenous N-acetyl-l-cysteine suppressed DC maturation. PLM treatment improved the severity of arthritis and reduced in vivo splenic DC maturation, collagen-specific CD4(+) T cell responses, and ROS production in mice with collagen-induced arthritis. Taken together, these results suggest that PLM inhibits DC maturation by reducing intracellular ROS production and has potential as a therapeutic agent for rheumatoid arthritis.
27159030 Association Between Breast Cancer Recurrence and Immunosuppression in Rheumatoid Arthritis 2016 Oct OBJECTIVE: Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune-mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti-tumor necrosis factor (anti-TNF). METHODS: Three retrospective cohort studies within Medicare (2000-2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti-TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy. RESULTS: Across all medication groups, 107 women experienced breast cancer recurrence during 5,196 person-years. The incidence rates were 20.3 and 19.6 per 1,000 person-years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti-TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67-1.69), anti-TNF therapy (HR 1.13, 95% CI 0.65-1.97), or thiopurines (HR 2.10, 95% CI 0.62-7.14). CONCLUSION: The risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti-TNF therapy was not statistically significantly increased, although we cannot rule out a 2-fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti-TNF therapy in RA or IBD patients with treated breast cancer.
26887552 [Antibodies to mutated citrullinated vimentin and some associated autoantibodies in juveni 2015 Dec OBJECTIVE: To compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers. METHOD: Antibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis. RESULT: (1) The positive rate of anti-MCV antibodies, anti-CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA. In the other group, the positive rate was 2.2%, 2.2%, and 6.5%. There was a significant difference between the two groups (χ(2)=8.105, 6.337, 7.036, P<0.05). The positive rate of AKA and APF were not significantly different. The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505. (2) The positive rate of anti-MCV antibodies and anti-CCP antibodies were higher than other antibodies. In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P<0.05). Antibody levels were not significantly different (P>0.05) from other subtypes. (3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. CONCLUSION: The diagnostic value of anti-MCV antibodies is low for JIA. The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA. There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts.
26909489 A phase I pharmacokinetics trial comparing PF-05280586 (a potential biosimilar) and rituxi 2016 Jul AIMS: Pharmacokinetic (PK) similarity was assessed among PF-05280586 (a proposed biosimilar) vs. rituximab sourced from the European Union (rituximab-EU) and the United States (rituximab-US). Pharmacodynamics (PD), overall safety and immunogenicity were also evaluated. METHODS: Patients with active rheumatoid arthritis on a background of methotrexate and inadequate response to one or more tumour necrosis factor antagonist therapies were randomized to intravenous PF-05280586, rituximab-EU or rituximab-US 1000 mg doses on study days 1 and 15. RESULTS: A total of 220 patients were randomized to receive study treatment as assigned. Of these, 198 met per-protocol population criteria for inclusion in the PK data analysis. PF-05280586, rituximab-EU and rituximab-US exhibited similar PK profiles following administration of assigned study drug on days 1 and 15. The 90% confidence intervals of test-to-reference ratios for Cmax , AUCT , AUC0-∞ and AUC2-week were within the bioequivalence margin of 80.00-125.00% for comparisons of PF-05280586 with rituximab-EU, PF-05280586 with rituximab-US, and rituximab-EU with rituximab-US. All treatments resulted in a rapid and profound reduction in CD19+ B cells and sustained profound B cell suppression up to week 25. The incidence of antidrug antibody (ADA) response (n = 7, 10 and 9 for PF-05280586, rituximab-EU and rituximab-US, respectively), time to ADA emergence and ADA titres were similar across treatments. None of the ADA-positive samples was positive for neutralizing activity. No clinically meaningful differences in adverse events were identified. CONCLUSIONS: The study demonstrated PK similarity among PF-05280586, rituximab-EU and rituximab-US. In addition, all treatments showed comparable CD19+ B cell depletion PD responses, as well as safety and immunogenicity profiles.