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

ID PMID Title PublicationDate abstract
20807656 Activated contact system and abnormal glycosaminoglycans in lupus and other auto- and non- 2010 Systemic lupus erythematosus (SLE), heparin-induced thrombocytopenia (HIT), rheumatoid arthritis (RA) are marked by the presence of autoantibodies against negatively changed DNA, phospholipids, heparin, and chondroitin sulfate, respectively. Heparin/protein complexes induce contact system activation in HIT patient plasmas. The activated contact system generates thrombin. Thrombin is responsible for thrombosis, a common cause of death and disabilities for both HIT and SLE. In this chapter, we analyze plasma contact system proteins, thrombin- and kallikrein-like activities, glucosamine and galactosamine content from SLE-, RA-, osteoarthritis (OA)-, and psoriasis (Ps)-patient plasmas in addition to pooled 30+ healthy patient plasmas. We found that all SLE patient plasmas exhibited abnormal contact systems marked by the absence of high molecular weight kininogen, the presence of processed C1 inhibitor (C1inh), the display of abnormal thrombin- and kallikrein-like activities, and increased levels of plasma glucosamine and galactosamine. Different patterns of contact system activation distinguish SLE, RA, and Ps whereas no contact system activation is observed in normal and OA patient plasmas. The presence of paradoxical "lupus anticoagulants" in certain thrombosis-prone SLE patient plasmas, marked by delayed clotting in clinical plasma test, was explained by the consumption of contact system proteins, especially high molecular weight kininogen. Finally, we discovered that mouse and human SLE autoantibodies bind to cell surface GAGs with structural selectivity. In conclusion, markers of abnormal contact system activation represent potential new targets for autoimmune disease diagnosis, prevention, and treatment. These markers might also be useful in monitoring SLE activity/severity and in pinpointing patients with SLE-associated arthritis and psoriasis.
19588142 Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-a 2010 Mar The aim of this study was to determine whether the rs7574865 polymorphism of STAT4 (signal transducers and activators of transcription 4) confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted on the T allele of the STAT4 rs7574865 polymorphism in 15 studies containing 16,088 RA patients and 16,509 normal control subjects. Meta-analysis revealed an association between RA and the STAT4 rs7574865 T allele in all subjects (OR = 1.271, 95% CI = 1.197-1.350, P < 0.001). Furthermore, the STAT4 rs7574865 T allele was found to be significantly associated with RA in Europeans and Asians (OR = 1.300, 95% CI = 1.195-1.414, P < 0.001; OR = 1.216, 95% CI = 1.135-1.303, P < 0.001). Stratification of RA patients according to the presence of anti-CCP antibody revealed a statistically significant association between the T allele and RA in both anti-CCP-positive and -negative RA patients versus controls. Europeans had the lowest (21.4%) and Asians had the highest (32.0%) prevalence of the T allele among the populations studied. In conclusion, this meta-analysis confirms that the STAT4 rs7574865 polymorphism is associated with RA susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.
19745701 Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastri 2009 Oct A 73-year-old woman with rheumatoid arthritis had been treated with weekly low-dose methotrexate (MTX) for 5 years. She suffered from epigastric discomfort. Endoscopic examination revealed a tumor resembling advanced gastric cancer. Biopsy specimens showed atypical lymphoid cell infiltration. Immunohistological studies showed that these cells were positive for CD30 and CD79a, but not for CD15 or CD20. In situ hybridization identified Epstein-Barr virus latency-associated RNA expression in these cells. Clonally rearranged immunoglobulin heavy chain JH gene was not detected by Southern blot analysis. She was diagnosed with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD) due to immunodeficiency caused by MTX administration. Cessation of MTX therapy led to complete regression of the tumor. To our knowledge, this is the first case of spontaneous remission of MTX-associated gastric LPD after discontinuation of MTX therapy. Increased awareness is needed on the possible occurrence of LPD resembling gastric cancer in rheumatoid arthritis patients treated with MTX.
19942106 "When I first started going I was going in on my knees, but I came out and I was skipping" 2009 Oct OBJECTIVES: To outline rheumatoid arthritis (RA) patients' experiences of receiving treatment with acupuncture, exploring the impact of practitioner affiliation to a traditional or western theoretical base. DESIGN: Qualitative study utilising grounded theory method. Convenience sample of thirteen patients with RA. Data collection, organisation and analysis performed concurrently. In-depth semi-structured interviews were tape-recorded and transcribed. Field notes were also taken. Open, axial and selective coding performed. Emergent categories and themes identified and informed the topics to be discussed in subsequent interviews. RESULTS: Patients perceived acupuncture as alleviating a number of RA symptoms including the relief of rheumatic pain and improvements in mobility. Acupuncture was additionally perceived as alleviating a number of consequential secondary symptoms of RA, such as fatigue, depression and sleeplessness. These effects allowed patients to feel normal again and regain their lives, and resulted in improvements in patients' lifestyle, emotional well-being and self-image. Acupuncturist affiliation impacts on both patient experience and perception of effects. CONCLUSIONS: Acupuncture elicits a range of effects which contribute to improvements in RA patients' quality of life. Varied levels of congruence were identified between the intended therapeutic effect of acupuncture [Hughes JG, Goldbart J, Fairhurst E, Knowles K. Exploring acupuncturists' perceptions of treating patients with rheumatoid arthritis. Complementary Therapies in Medicine 2007;15:101-8] and patients' perceptions of effects. Acupuncturist affiliation has demonstrable implications for the practice and research of acupuncture.
19171130 Mizoribine may suppress bone erosion in patients with rheumatoid arthritis by inhibiting o 2009 Mar 1 Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of rheumatoid arthritis. However, clinical use of the drug is restricted to a few Asian countries due to a lack of comprehensive evidence on its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis was investigated in the hopes of providing some clear evidence. Mizoribine was found to inhibit in vitro osteoclastogenesis in a dose-dependent manner. In addition, the size of the pit area was closely related to the number of osteoclasts in a bone resorption assay. However, mizoribine did not affect the phosphorylation of MAP kinase (p38, JNK, ERK), the degradation of IkappaBalpha, or receptor activator of NF-kappaB ligand (RANKL) expression in fibroblast-like synoviocytes stimulated with IL-1beta. These results suggested that mizoribine may partially suppress osteoclastogenesis, leading to progressive bone erosion by inhibiting the growth or the signaling pathway of precursor cells to form osteoclasts rather than fibroblast-like synoviocytes.
18535114 Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results fro 2009 Feb OBJECTIVES: To determine the association between risk of rheumatoid arthritis (RA) and alcohol consumption in combination with smoking and HLA-DRB1 shared epitope (SE). METHODS: Data from two independent case-control studies of RA, the Swedish EIRA (1204 cases and 871 controls) and the Danish CACORA (444 cases and 533 controls), were used to estimate ORs of developing RA for different amounts of alcohol consumed. RESULTS: Alcohol consumption was significantly more common in controls (p<0.05) and dose-dependently associated with reduced risk of RA (p for trend <0.001) in both studies. Among alcohol consumers, the quarter with the highest consumption had a decreased risk of RA of the order of 40-50% compared with the half with the lowest consumption (EIRA, OR = 0.5 (95% CI 0.4 to 0.6); CACORA, OR = 0.6 (95% CI 0.4 to 0.9)). For the subset of RA that is seropositive for antibodies to citrullinated peptide antigens, alcohol consumption reduced the risk most in smokers carrying HLA-DRB1 SE alleles. CONCLUSIONS: The observed inverse association between alcohol intake and risk of RA and the recent demonstration of a preventive effect of alcohol in experimental arthritis indicate that alcohol may protect against RA. This highlights the potential role of lifestyle in determining the risk of developing RA, and emphasises the advice to stop smoking, but not necessarily to abstain from alcohol in order to diminish risk of RA. The evidence of potential RA prevention should prompt additional studies on how this can be achieved.
21063071 Genetic polymorphisms of the DNA repair gene MPG may be associated with susceptibility to 2010 Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. A previous study indicated that a DNA repair system was involved in the development of RA. In this study, we investigated the association of four N-methylpurine-DNA glycosylase (MPG) gene polymorphisms (rs3176364, rs710079, rs2858056, and rs2541632) with susceptibility to RA in 384 Taiwanese individuals (192 RA patients and 192 control subjects). Our data show a statistically significant difference in genotype frequency distributions at rs710079 and rs2858056 SNPs between RA patients and control groups (P = 0.040 and 0.029, respectively). Our data also indicated that individuals with the GG genotype at rs2858056 SNP may have a higher risk of developing RA. In addition, compared with the haplotype frequencies between case and control groups, individuals with the GCGC haplotype appeared to be at a greater risk of RA progression (P = 0.003, OR = 1.75; 95% CI = 1.20-1.55). Our results suggest that rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of RA progression, and thus may be used as molecular markers of RA if they are confirmed by further research.
20337633 Effects of long-term disease-modifying antirheumatic drugs on endothelial function in pati 2010 Oct Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.
18408246 Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arr 2009 Mar OBJECTIVE: To explore the effects of anti-tumour necrosis factor (TNF)alpha antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA). METHODS: A total of 50 patients with active RA (DAS28> or =3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (< or =10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment. RESULTS: Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (-0.7%), (p = 0.015). CONCLUSION: In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects.
21351303 The reliability of diagnostic coding and laboratory data to identify tuberculosis and nont 2011 Mar PURPOSE: Anti-tumor necrosis factor-alpha (anti-TNF) therapies are associated with severe mycobacterial infections in rheumatoid arthritis patients. We developed and validated electronic record search algorithms for these serious infections. METHODS: The study used electronic clinical, microbiologic, and pharmacy records from Kaiser Permanente Northern California (KPNC) and the Portland Veterans Affairs Medical Center (PVAMC). We identified suspect tuberculosis and nontuberculous mycobacteria (NTM) cases using inpatient and outpatient diagnostic codes, culture results, and anti-tuberculous medication dispensing. We manually reviewed records to validate our case-finding algorithms. RESULTS: We identified 64 tuberculosis and 367 NTM potential cases, respectively. For tuberculosis, diagnostic code positive predictive value (PPV) was 54% at KPNC and 9% at PVAMC. Adding medication dispensings improved these to 87% and 46%, respectively. Positive tuberculosis cultures had a PPV of 100% with sensitivities of 79% (KPNC) and 55% (PVAMC). For NTM, the PPV of diagnostic codes was 91% (KPNC) and 76% (PVAMC). At KPNC, ≥ 1 positive NTM culture was sensitive (100%) and specific (PPV, 74%) if non-pathogenic species were excluded; at PVAMC, ≥1 positive NTM culture identified 76% of cases with PPV of 41%. Application of the American Thoracic Society NTM microbiology criteria yielded the highest PPV (100% KPNC, 78% PVAMC). CONCLUSIONS: The sensitivity and predictive value of electronic microbiologic data for tuberculosis and NTM infections is generally high, but varies with different facilities or models of care. Unlike NTM, tuberculosis diagnostic codes have poor PPV, and in the absence of laboratory data, should be combined with anti-tuberculous therapy dispensings for pharmacoepidemiologic research.
20511978 Adalimumab-induced acute pneumonitis in a patient with rheumatoid arthritis. 2010 Jun Interstitial lung disease is one of the most common and severe extra-articular manifestations associated with rheumatoid arthritis. Previous to the biologic treatment era, methotrexate was the medication known to cause acute lung disease mostly in patients with preexisting rheumatoid lung disease. However, recent case reports of patients treated with biologic therapies show an increased incidence of acute lung disease caused by tumor necrosis factor alpha inhibitors. This case will illustrate acute lung disease caused by adalimumab, a recombinant IgG1 monoclonal antibody. The rheumatology community must be aware of this adverse effect described so far with all 3 major tumor necrosis factor alpha inhibitors, before starting but also during maintenance therapy.
18339663 The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mo 2009 Jan OBJECTIVES: The viral gene transfer of interleukin 1 receptor antagonist (IL1ra) and interleukin 10 (IL10) into rheumatoid arthritis (RA) synovial fibroblasts (RASFs) has shown protective effects on cartilage destruction in the severe combined immunodeficiency (SCID) mouse model of RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost and time intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID mouse model for RA. METHODS: Isolated RASFs were cultured for four passages and coimplanted together with human cartilage and an Alzet osmotic miniature pump model 2004, containing 200 microl of IL10 and IL1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL10 and IL1ra in murine serum were measured by ELISA. RESULTS: Release of IL10 and IL1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL10 and IL1ra release showed protective effects towards the coimplanted cartilage, similar to the adenovirally IL10/IL1ra-transduced RASFs. The mean (SD) invasion scores for the implants with the osmotic pumps were: invasion 0.7 (0.5), degradation 0.5 (0.3) (all parameters significant vs controls, p<0.05). CONCLUSIONS: The results demonstrate that the combination of osmotic pumps with the SCID mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.
20464755 Balance training (proprioceptive training) for patients with rheumatoid arthritis. 2010 May 12 BACKGROUND: Patients with rheumatoid arthritis may have an increased risk of falls due to impairments in lower-extremity joints, which may result in either mobility, or postural stability problems. There is evidence in the literature suggesting that balance, agility and coordination training techniques can induce changes in lower-extremity muscle activity patterns that result in improvement in dynamic joint stability.The mechanoreceptors present in and around the joints are responsible for maintaining postural control and joint position sense. These receptors are integrated to compose the somatosensorial system. In combination with visual and auditory inputs, which improve our spatial perception even further, the systems are able to maintain a stable body posture.However, there is a lack of information on the efficacy of balance training alone in patients with rheumatoid arthritis. OBJECTIVES: To assess the effectiveness and safety of balance training (proprioceptive training) to improve functional capacity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE via PubMed (January 1966 to December 2008), EMBASE (January 1980 to December 2008), LILACS (January 1982 to December 2008), CINAHL (January 1982 to December 2008), PEDro and Scirus (inception to 2008). We also handsearched conference abstracts. SELECTION CRITERIA: All eligible randomised controlled trials (RCT) or controlled clinical trials (CCT) comparing balance training (proprioceptive training) with any other intervention or with no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles or abstracts, or both, for inclusion criteria. MAIN RESULTS: The electronic search identified 864 studies. From this search, 17 studies described general exercises in rheumatoid arthritis patients as the main topic. After analysing them, we observed that the main interventions were exercises to improve muscle strength, endurance, and dynamic exercises (swimming, walking, etc). As we did not find any studies investigating the effects of balance training alone or in combination with other therapies in patients with rheumatoid arthritis, it was not possible to include any data regarding the chosen topic in this systematic review. AUTHORS' CONCLUSIONS: There is no research available examining the efficacy of balance training alone in patients with rheumatoid arthritis. The effectiveness and safety of balance training to improve functional capacity of these patients remains unclear. We suggest that future research should give more importance to balance training by either increasing the number and duration of sessions or investigating its efficacy alone.
19598316 Radiolunate fusion with distraction using corticocancellous bone graft for minimizing decr 2009 Radiolunate fusion is a limited carpal fusion procedure used for patients with rheumatoid arthritis. However, this procedure inevitably causes decreases in range of motion, especially wrist flexion. Linscheid and Dobyns described the possibility of minimizing the decrease in motion at the radiocarpal joint by slight distraction of the joint. We hypothesized for our modified procedure that a corticocancellous bone graft was inserted between the radius and the lunate with a small amount of over-correction could provide slight distraction of radioscaphoid joint and protect the joint from decreased range of motion after arthrodesis. Twelve wrists in ten patients with rheumatoid arthritis underwent radiolunate fusion. Mean age at operation was 53 years old and mean follow-up period was 5.7 years. Clinical evaluation and radiological assessment showed that decrease in range of motion was minimized compared with other procedures. Because our modified procedure can minimize decrease in motion, it is recommended.
20883838 Injectable hyaluronic acid-tyramine hydrogels for the treatment of rheumatoid arthritis. 2011 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading in turn to articular cartilage destruction. In this work, injectable tyramine modified hyaluronic acid (HA-Tyr) hydrogels were developed for the treatment of RA. HA-Tyr conjugate was synthesized by amide bond formation between carboxyl groups of HA and amine groups of tyramine. Then, HA-Tyr hydrogels were prepared by radical crosslinking reaction using H(2)O(2) and horse-radish peroxidase. Intra-articular injection of HA-Tyr hydrogels encapsulating dexamethasone (DMT) as a model drug resulted in successful treatment of RA with reduced interlukine-6, prostaglandin E2 and four types of cytokine levels in collagen-induced arthritis animal models. Histological analysis with hematoxylin and eosin (H&E) staining also confirmed the therapeutic effect of injectable HA-Tyr hydrogels with DMT. Taken together, the injectable HA-Tyr hydrogels were thought suitable to be developed as a therapeutically effective drug carrier for the treatment of RA.
20210795 Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis pa 2010 May Among methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPD), diffuse large B-cell lymphoma (DLBCL) accounts for about half. We studied the clinicopathological characteristics and prognosis of patients with DLBCL in MTX-LPD. This study included 29 patients who developed DLBCL after receiving MTX for rheumatoid arthritis. MTX was discontinued in all patients. Their median age was 62 years. Elevated lactate dehydrogenase (LDH) level was observed in 97% of the patients, bone marrow involvement in 17%, and involvement of extranodal sites in 41%. As for the cellular immunophenotype, CD20 was positive in 93%, CD5 in 3%, CD10 in 31%, BCL2 in 21%, BCL6 in 69%, and Epstein-Barr virus (EBV)-encoded small non-polyadenylated RNA (EBER) in 24%. Chemotherapy was started within 2 months after MTX withdrawal in 23 patients, of whom 12 patients received combination with rituximab. Spontaneous remission occurred in the remaining six patients. The EEBV-positive rate was 67% (4/6), and the four EBV-positive patients achieved complete response. Among the 23 DLBCL patients treated with chemotherapy, 20 patients achieved complete response. The 5-year overall survival was 74% and the 5-year progression-free survival was 65%. After the development of DLBCL, withdrawal of MTX was the first choice of treatment. Germinal center B-cell type and EBER-positive patients tended to show spontaneous remission. The utility of rituximab should be examined in future studies.
19466615 Tight control is important in patients with rheumatoid arthritis treated with an anti-tumo 2009 The purpose of this study is to identify the factors that require arthroplasty due to the progression of joint destruction, even when an anti-tumor necrosis factor (TNF) biological agent is used for rheumatoid arthritis (RA). Among 91 cases that used the anti-TNF biological agent for more than 1 year, two groups of 21 cases that resulted in arthroplasty (surgery group) and 70 cases that did not result in arthroplasty (non-surgery group) were compared and examined. When the anti-TNF biological agent was first administered, disease activity and internal use of glucocorticoid (PSL) were not different in these two groups. The average DAS28-CRP(4) (disease activity score including a 28-joint count/C-reactive protein) (p < 0.001) and the amount of internal use of PSL (p < 0.05) were significantly decreased in the non-surgery group compared with the surgery group at the final survey. To inhibit the need for joint surgery in patients using the anti-TNF biological agent, it is important to maintain tight control over RA activity.
19234208 Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arth 2009 Mar 1 IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; however, the contribution of IL-17F remains to be clarified. Using microarrays and gene-specific expression assays, we compared the regulatory effects of IL-17A and IL-17F alone or in combination with TNF-alpha on RA synoviocytes. IL-17A and IL-17F expression was studied in osteoarthritis and RA synovium by immunohistochemistry. The comparison between the IL-17A and IL-17F stimulatory effect on RA synoviocytes was assessed at the protein level by ELISA and at the mRNA level by microarrays and real-time RT-PCR. TNFRII expression was studied by real-time RT-PCR and immunofluorescence, and neutralizing Ab was used to analyze its contribution to CCL20 secretion. IL-17A and IL-17F were detected in plasma cell-like cells from RA but not osteoarthritis synovium. In microarrays, IL-17A and IL-17F alone had similar regulatory effects, IL-17F being quantitatively less active. Both cytokines induced a similar expression pattern in the presence of TNF-alpha. Based on a cooperation index, 130 and 203 genes were synergistically induced by IL-17A or IL-17F plus TNF-alpha, respectively. Among these, the new target genes CXCR4, LPL, and IL-32 were validated by real-time RT-PCR. IL-17A and IL-17F up-regulated TNFRII expression, but had no effects on TNFRI, IL-17RA or IL-17RC. TNFRII blockade inhibited the synergistic induction of CCL20 by IL-17A or IL-17F and TNF-alpha. IL-17A and IL-17F are both expressed in RA synovium. In the presence of TNF-alpha, they induced a similar expression pattern in RA synoviocytes. Accordingly, IL-17F appears as a target in Th17-mediated diseases such as RA.
21142617 Persistence with non-selective NSAIDs and celecoxib among patients with gastroesophageal r 2011 Feb OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients taking nonselective, nonsteroidal anti-inflammatory drugs (nsNSAIDs) and are often a reason for therapy discontinuation. In osteoarthritis (OA) and rheumatoid arthritis (RA) patients requiring pain control, selective COX-2 NSAID use is typically associated with less dyspepsia than is nsNSAID use. Little is known about NSAID tolerance in patients with gastroesophageal reflux disease (GERD). This study assessed nsNSAID and celecoxib prescription patterns, in particular persistence, in OA/RA patients with concomitant diagnosis of GERD. METHODS: An observational study of GERD patients with a diagnosis of OA/RA using two separate databases, the IMS Lifelink Health Plan Claims Database (PharMetrics) and Market Scan Claims Database (Medstat) was conducted. In each database, parallel and separate analyses were performed in adult patients who had their first GERD diagnosis in 2006 and who were subsequently diagnosed with OA or RA in the same year. From this subset of patients, celecoxib-naïve and nsNSAID-naïve cohorts were identified and patients were selected. Patients with pre-existing GI conditions were excluded from the study. Persistence, measured as time to discontinuation, was evaluated by Kaplan-Meier survival curves and Cox proportional hazards models. Reasons for discontinuations were not available in these databases. RESULTS: Fewer patients discontinued celecoxib as compared to nsNSAIDs during the 60 days of the first prescription and throughout the entire follow-up period. After adjusting for baseline characteristics, celecoxib patients still had significantly decreased risk of discontinuation as compared to nsNSAID patients (p < 0.0001). Replication of these observations in two separate, large patient databases increases the confidence in this study's conclusion. LIMITATIONS: Limitations include those inherent to claims data analyses and retrospective review, e.g. these data do not provide clinical information related to reasons for medication discontinuation. CONCLUSION: In patients with concomitant GERD and OA or RA who require anti-inflammatory treatment, significantly more patients treated with celecoxib were persistent with their treatment than were patients treated with nsNSAIDs.
19966090 Silica exposure among male current smokers is associated with a high risk of developing AC 2010 Jun OBJECTIVE: To study the association between silica exposure, separately as well as combined with smoking, and the risk of developing rheumatoid arthritis (RA) with or without the presence of antibodies against citrullinated peptide antigens (ACPA). METHODS: This Swedish population based case-control study analysed 577 incident RA cases and 659 randomly selected controls, all men aged 18-70 years, included during May 1996 to May 2006. Self-reported silica exposure, defined as exposure to stone dust, rock drilling or stone crushing and cigarette smoking was registered. ACPA status among cases was analysed. RESULTS: Silica-exposed subjects were found to have a moderately increased risk of ACPA-positive RA (odds ratio (OR) adjusted for age and residency=1.67 (95% CI 1.13 to 2.48), but not of ACPA-negative RA (OR=0.98 (95% CI 0.57 to 1.66)), compared with subjects unexposed to silica. SUBJECTS: exposed to rock drilling were found to have a somewhat more markedly increased risk of ACPA-positive RA (OR=2.34 (95% CI 1.17 to 4.68)). A high risk of developing ACPA-positive RA was observed among silica-exposed current smokers (OR=7.36 (95% CI 3.31 to 16.38)), exceeding the risk expected from the separate effects of silica exposure and current smoking, indicating an interaction between these exposures (attributable proportion due to interaction=0.60 (95% CI 0.26 to 0.95)). CONCLUSION: Silica exposure combined with smoking among men is associated with an increased risk of developing ACPA-positive RA. These results suggest that different inhalation exposures may interact in the aetiology of ACPA-positive RA.