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ID PMID Title PublicationDate abstract
22179739 Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic disease 2012 Apr OBJECTIVES: Polymorphisms in genes related to the IFN pathway were investigated for susceptibility to rheumatic diseases and correlation with gene expression in thymus. METHODS: Forty-five polymorphisms were genotyped in Norwegian patients with RA (n = 518), JIA (n = 440), SLE (n = 154) and healthy controls (n = 756). Forty-two thymic samples were used for gene expression analysis. Six hundred and fifty SLE patients and 737 healthy controls from Spain were available for replication. RESULTS: We found a novel association between interferon regulatory factor 5 (IRF5), rs2004640 and JIA, in particular with the polyarthritis RF-negative patients [odds ratio (OR) = 1.60; 95% confidence interval (CI) 1.17, 2.20; P = 0.003]. Also, we confirmed the associations between rs2004640 and SLE (OR = 1.95; 95% CI 1.50, 2.53; P = 3.75 × 10(-7)), which was further strengthened in a meta-analysis (OR = 1.44; 95% CI 1.36, 1.52; P = 2.11 × 10(-37)). Suggestive evidence of association between rs2004640 and RA was found in the Norwegian discovery cohort (OR = 1.19; 95% CI 1.02, 1.40; P = 0.029) and strengthened in a meta-analysis (OR = 1.11; 95% CI 1.05, 1.18; P = 0.00028). Expression levels of exon 1B IRF5 transcripts were dependent on the presence of the rs2004640 T risk allele in thymic tissue, while exon 1A transcript levels correlated with IRF5 promoter CGGGG-indel variants. CONCLUSION: The IFN pathway gene, IRF5, is a common susceptibility factor for several rheumatic and autoimmune diseases, and risk variants are correlated with expression of alternative IRF5 transcripts in thymus implying a regulatory role.
21873268 Negotiating targets with patients: choice of target in relation to occupational state. 2012 Feb OBJECTIVES: Following the recent National Institute for Health and Clinical Excellence guidance on the management of RA, we were interested to see if we could negotiate targets for treatment with patients in routine clinics, how they would express this and whether staying at work would be a target. METHODS: One hundred RA patients were recruited. They were consecutive within clinics, but not all clinics were used. They were asked their understanding of the DAS score and a target for treatment negotiated. Any impact of the RA on their paid employment was then explored. RESULTS: Four participants were unable to specify a target for their RA. Negotiated targets were expressed as restricted activities and either as maintaining an activity (70) if the disease was stable, or regaining an activity (26) if the treatment was being increased. Targets were walking a distance for 50% of patients; leisure activities for 18%; domestic activities for 17%; work for 14% and personal care for 2%. For the 21 participants currently working, maintaining work was the target for 12, with 1 wishing to regain lost hours. No patient currently not working expressed returning to work as a target. There were some differences in targets between men and women. CONCLUSIONS: Patients are able to negotiate a target for their treatment, expressed as maintaining or regaining a physical activity. Work ceases to be a target once it is lost. Therefore, preventing loss of occupation is likely to be more effective than trying to regain it.
22209319 [Vitamin D and autoimmunity. Second part: Clinical aspects]. 2012 Feb Vitamin D is often confined to its role in calcium homeostasis and bone metabolism. An exponential literature discusses its non-skeletal effects, especially its central role in the physiology of the immune system, where it acts at several levels to maintain self-tolerance. Here, the authors review the experimental, epidemiological and clinical studies, illustrating the potential role of vitamin D in the development and perpetuation of autoimmune diseases such as systemic lupus erythematosus, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases or rheumatoid arthritis.
22174201 Effectiveness of rituximab in patients with rheumatoid arthritis: observational study from 2012 Feb OBJECTIVE: To assess the effectiveness of rituximab (RTX) in patients with rheumatoid arthritis (RA) in routine clinical practice, and to identify predictors of 6-month response to RTX in patients for whom at least 1 anti-tumor necrosis factor-α (anti-TNF) therapy has failed. METHOD: The analysis involved 646 patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR) who were starting RTX and were followed for at least 6 months. Change in the 28-joint Disease Activity Score (DAS28), European League Against Rheumatism (EULAR) response, and proportions of patients achieving disease remission were used to assess the clinical response 6 months after starting RTX. Regression analyses were used to identify factors associated with the response in the patients for whom anti-TNF therapy had not worked. The models included baseline demographics, disease characteristics, baseline Health Assessment Questionnaire (HAQ), and drug history including biologic history. RESULTS: The mean DAS28 at baseline was 6.2 (95% CI 6.1, 6.3), which decreased significantly to 4.8 (95% CI 4.7, 4.9) at the 6-month followup. Seventeen percent of the patients were EULAR good responders and 43% were moderate responders. Eight percent of the patients achieved disease remission. Subjects with higher baseline DAS28 score and those with positive rheumatoid factor (RF) status were significantly associated with a decrease in their DAS28 score (improvement), while women and patients with higher baseline HAQ score were less likely to improve. CONCLUSION: RTX has proven to be effective in routine clinical practice. When anti-TNF therapy fails, response to RTX was influenced by baseline DAS28 score, RF status, baseline HAQ score, and sex.
21305388 Trichostatin differentially regulates Th1 and Th2 responses and alleviates rheumatoid arth 2011 Jun OBJECTIVE: Histone deacetylase inhibitors have shown suppressive effects on tumor growth and in some autoimmune diseases. However, the molecular mechanisms of their effects are not very clear. The purpose of this study was to investigate the effects of trichostatin A (TSA) on collagen-induced rheumatoid arthritis (CIA) in a mouse model and its underlying mechanisms. METHODS: CIA was induced in DBA/1 mice with type II collagen. Paws were scored to assess disease severity. Inflammation of joints was evaluated by histological examination. Real-time PCR was used to determine cytokine mRNA levels. Cytokine production in serum and in supernatants from dendritic to T cell co-cultures was measured by ELISA. T cell proliferation was determined using [(3)H] incorporation. Intracellular cytokine staining was used to measure interferon gamma (IFN-γ)- and interleukin (IL)-4-producing T cells in splenocytes. Chromatin immunoprecipitation was used to examine histone H3 and H4 acetylation. RESULTS: TSA potently suppressed the severity of arthritis and type II collagen-specific T cell responses in CIA. IFN-γ expression was high in CIA mice, but was inhibited by TSA treatment either at the same time as immunization or at the onset of arthritis manifestation. T cells from TSA-treated mice produced higher levels of IL-4 than cells from the control group. TSA predominantly suppressed Th1 cell proliferation in vitro by induction of apoptosis. In addition, TSA enhanced IL-4 gene expression of in vitro differentiated Th2 cells, and the mechanism is associated with an increased level of histone acetylation in the IL-4 gene promoter. CONCLUSIONS: While TSA selectively suppresses a Th1 response by inducing apoptosis, it upregulates IL-4 expression probably by increasing histone H3 and H4 acetylation of the IL-4 gene promoter. We conclude that TSA can induce a Th1/Th2 balance in vivo and exert protective effects on CIA.
21873332 Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic inte 2011 Nov BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. METHODS: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. RESULTS: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.
21826567 [Inflammatory diseases of the spinal column and the myelon]. 2011 Sep Inflammatory diseases of the spine and the spinal cord (myelon) can be caused by a wide range of pathological conditions. Except for degenerative inflammatory diseases of the spine, infectious and autoimmune disorders are relatively rare. The latter can also be a significant source of pain and disability, especially if these hard to diagnose conditions go untreated. In cases of advanced disease some entities, such as spondylodiscitis or rheumatoid arthritis can cause severe neurological impairment especially by progressive intraspinal spread. Inflammation of the myelon cannot be depicted with conventional radiographs in general and by computed tomography only occasionally. In these cases magnetic resonance imaging is the method of choice to detect early abnormalities of the myelon and to provide detailed information for the differential diagnosis.
22461187 Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumato 2013 Feb We determined the prevalence of work disability in early rheumatoid arthritis (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR criteria versus those not meeting criteria, to determine the impact of meeting new criteria on work disability status. Data at first visit into the cohort were analyzed. Descriptive statistics and logistic regression analyses were performed to investigate the association of other variables in our database with work disability. 1,487 patients were enrolled in the CATCH study, a multi-site observational, prospective cohort of patients with EIA. 934 patients were excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP was absent, and 429 were not working for other reasons). Of the 553 patients included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %) were employed while 29 (5.2 %) reported work disability at first visit. There were no differences between those meeting 2010 ACR criteria versus those who did not. Baseline characteristics associated with work disability were male gender, age, education, income, HAQ, and positive RF status. The mean HAQ score in work disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001). Disease activity score (DAS28) was not associated with work disability (p = 0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global assessment, or SF-12v2. In the regression model, work disability was associated with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001), but not significantly associated with male gender (p = 0.08), older age (>50 years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found rates of work disability to be low at entry into this EIA cohort compared to previous studies. There may be potential for intervention in ERA to prevent the development of work disability.
23222800 Autoimmune thyroid diseases and nonorgan‑specific autoimmunity. 2012 Autoimmune thyroid diseases (ATD), as the most common organ‑specific autoimmune disorder, is frequently accompanied by other organ- and nonorgan‑specific autoimmune diseases. Although the exact pathogenic mechanism of the coexistence of autoimmune disorders has not been clearly defined, genetic and environmental factors, immune defects, and hormonal changes, may play a key role in polyautoimmunity. The role of human leukocyte antigen (HLA) haplotypes, HLA-B8 and -DR3, in the overlapping of autoimmune disorders was well supported by higher frequency of these haplotypes in primary Sjögren's syndrome (PSS) and ATD. In addition, polymorphisms of the cytotoxic T lymphocytic antigen 4 gene have been reported to be associated with many autoimmune disorders especially those coexisting with ATD. Definite noncasual association of ATD has been clearly documented in patients with PSS, rheumatoid arthritis, and systemic lupus erythematosus. Possible association with ATD is also considered in systemic sclerosis and dermatomyositis. Many authors documented a significantly higher prevalence of antinuclear antibodies (ANAs) in ATD patients in comparison with controls; however, the clinical significance of ANAs in this group is still unknown. The presence of other non‑organ‑specific antibodies has not been convincingly demonstrated. On the other hand, the prevalence of antithyroid antibodies as well as ATD is higher in patients with systemic connective tissue disease compared with the general population. Basedon these data, there is no evidence for the utility of ANA testing in patients with ATD, but because of the high prevalence of ATD and antithyroid autoantibodies, it is clinically important to screen patients with autoimmune rheumatic disorders for the presence of thyroid autoimmunity.
22393877 Estrogen inhibits apoptosis and promotes CC motif chemokine ligand 13 expression on synovi 2012 Oct OBJECTIVE: Female patients have a higher prevalence of rheumatoid arthritis (RA) than male patients, suggesting that female sex hormones contribute to the disease pathogenesis. We herein report the findings of our study, which was conducted to clarify the role of estrogen in the pathogenesis of RA. METHODS: Cultured human synovial fibroblasts from a patient with RA were treated with 17β-estradiol (E(2)). The effects of E(2) against cellular activation and apoptosis were evaluated. To identify the disease-related genes altered by E(2) treatment, the changes in the gene expression of the cells stimulated with and without E(2) were evaluated using a microarray analysis. RESULTS: We found that E(2)-mediated cellular activation signaling through extracellular signal-regulated kinase (ERK)-1/2. E(2) possessed a suppressive effect for apoptosis and a promotive effect for tumor necrosis factor (TNF)-α-induced matrix metalloproteinase (MMP)-3 production on the synovial fibroblasts. A microarray analysis revealed that E(2) profoundly upregulated CC motif chemokine ligand 13 (CCL13) gene expression. CONCLUSIONS: E(2) could mediate cellular activation signaling through ERK-1/2 on the synovial fibroblasts. The present data suggest that E(2) has adverse effects on the pathogenesis of RA as a result of unregulated cell death, increased TNF-α-induced MMP-3 production, and CCL13 overproduction, subsequently resulting in the disease progression of RA.
23160550 Replacement with silicone wrist implant after failed silicone wrist arthroplasty: 3 case r 2012 Dec Revision surgery after failed silicone wrist arthroplasty is often challenging. In particular, in cases of inflammatory arthritis there is a high incidence of extensive bone loss which leads to a high complication rate in wrist fusion as a salvage procedure. Sometimes the surgeon may be faced with a patient in poor overall medical condition, who is very low demand so that the complexities of wrist fusion after a failed silicone arthroplasty may be contraindicated. For that situation, revision with a silicone prosthesis is a easy method in cases of severe osseous destruction in low demand patients with a long history of inflammatory arthritis.With 3 case reports will describe the topic of replacement with silicone wrist implant after failed silicone wrist arthroplasty.
21884580 Inhibitory effects of the JAK inhibitor CP690,550 on human CD4(+) T lymphocyte cytokine pr 2011 Aug 31 BACKGROUND: The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4(+) T cells. RESULTS: CD4(+) T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4(+) T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70. CONCLUSIONS: Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.
21604524 [Comparison of the status of STAT4 tyrosine phosphorylation in peripheral T-lymphocytes in 2011 Apr OBJECTIVE: To compare the levels of STAT4 tyrosine phosphorylation in peripheral T-lymphocytes induced by IL-12 in rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: From May 2007 to August 2009, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients [RA group, all the cases were female, the age was from 28 to 55 years with an average of (45.0 +/- 13.0) years] and OA patients [OA group, all the cases also were female; the age was from 55 to 75 years with an average of (67.0 +/- 9.6) years]. The purity of T-lymphocytes from PBMCs was accredited by flow cytometry. The IL-12 of 50 ng/ml added in T-lymphocytes, the levels of STAT4 tyrosine phosphorylation were detected by western blot after different time intervals (0, 10, 30, 60 min). RESULTS: The purity of T-lymphocytes were above 91% through diremption and depuration for peripheral blood monouclear cells. The levels of STAT4 tyrosine phosphorylation in T-lymphocytes from RA induced by IL-12 were higher than that from OA in the different times (10, 30, 60 min); after 30 min, its levels from RA and OA achieved to crest value. CONCLUSION: STAT4 in peripheral T-lymphocytes of rheumatoid arthritis was more easily to be activated than osteoarthritis.
22251436 Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatme 2012 Jan 17 INTRODUCTION: The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX). METHODS: This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components. RESULTS: Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%). CONCLUSIONS: Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00427934.
21121942 Iatrogenic oral hairy leukoplakia: report of two cases. 2011 Mar Oral hairy leukoplakia (OHL) presents as a white, plaque-like lesion typically occurring on the lateral border of the tongue. This condition is caused by the Epstein-Barr virus, a human herpesvirus that often establishes lifelong, asymptomatic latent infection. OHL, initially described in immunocompromised men infected with the human immunodeficiency virus (HIV), has also been described in other severely immunocompromised patients. Only rarely has OHL been reported in less profoundly immunocompromised patients primarily in the setting of corticosteroid therapy. Here we report on two additional cases of OHL attributable to immunosuppressive medications.
22294469 Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells. 2012 Jul OBJECTIVE: Tissue glucocorticoid (GC) levels are regulated by the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme is expressed in cells and tissues arising from mesenchymal stromal cells. Proinflammatory cytokines dramatically increase expression of 11β-HSD1 in stromal cells, an effect that has been implicated in inflammatory arthritis, osteoporosis, obesity, and myopathy. Additionally, GCs act synergistically with proinflammatory cytokines to further increase enzyme expression. The present study was undertaken to investigate the mechanisms underlying this regulation. METHODS: Gene reporter analysis, rapid amplification of complementary DNA ends (RACE), chemical inhibition experiments, and genetic disruption of intracellular signaling pathways in mouse embryonic fibroblasts (MEFs) were used to define the molecular mechanisms underlying the regulation of 11β-HSD1 expression. RESULTS: Gene reporter, RACE, and chemical inhibitor studies demonstrated that the increase in 11β-HSD1 expression with tumor necrosis factor α (TNFα)/interleukin-1β (IL-1β) occurred via the proximal HSD11B1 gene promoter and depended on NF-κB signaling. These findings were confirmed using MEFs with targeted disruption of NF-κB signaling, in which RelA (p65) deletion prevented TNFα/IL-1β induction of 11β-HSD1. GC treatment did not prevent TNFα-induced NF-κB nuclear translocation. The synergistic enhancement of TNFα-induced 11β-HSD1 expression with GCs was reproduced by specific inhibitors of p38 MAPK. Inhibitor and gene deletion studies indicated that the effects of GCs on p38 MAPK activity occurred primarily through induction of dual-specificity phosphatase 1 expression. CONCLUSION: The mechanism by which stromal cell expression of 11β-HSD1 is regulated is novel and distinct from that in other tissues. These findings open new opportunities for development of therapeutic interventions aimed at inhibiting or stimulating local GC levels in cells of mesenchymal stromal lineage during inflammation.
21131967 Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone met 2011 Jan Signaling via the methylation of lysine residues in proteins has been linked to diverse biological and disease processes, yet the catalytic activity and substrate specificity of many human protein lysine methyltransferases (PKMTs) are unknown. We screened over 40 candidate PKMTs and identified SETD6 as a methyltransferase that monomethylated chromatin-associated transcription factor NF-κB subunit RelA at Lys310 (RelAK310me1). SETD6-mediated methylation rendered RelA inert and attenuated RelA-driven transcriptional programs, including inflammatory responses in primary immune cells. RelAK310me1 was recognized by the ankryin repeat of the histone methyltransferase GLP, which under basal conditions promoted a repressed chromatin state at RelA target genes through GLP-mediated methylation of histone H3 Lys9 (H3K9). NF-κB-activation-linked phosphorylation of RelA at Ser311 by protein kinase C-ζ (PKC-ζ) blocked the binding of GLP to RelAK310me1 and relieved repression of the target gene. Our findings establish a previously uncharacterized mechanism by which chromatin signaling regulates inflammation programs.
21885884 The effects of daily weather on accelerometer-measured physical activity. 2011 Sep BACKGROUND: This study analyzes Chicago-area weather effects on objectively measured physical activity over a 3-year period among a cohort of 241 participants in an on-going arthritis physical activity trial. METHODS: Uniaxial accelerometer counts and interview data were analyzed for up to 6 weekly study waves involving 4823 days of wear. The effects of temperature, rainfall, snowfall and daylight hours were analyzed after controlling for participant characteristics, day of the week, and daily accelerometer wear hours in a mixed effects linear regression model. RESULTS: Daylight hours, mean daily temperature < 20 or ≥ 75 degrees, and light or heavy rainfall (but not snowfall) were all significantly associated with lower physical activity after controlling for the significant effects of weekends, accelerometer wear hours, age, sex, type of arthritis, employment, Hispanic ethnicity, obesity, and SF36 physical and mental health scores. CONCLUSIONS: The cumulative effects of weather are reflected in a 38.3% mean monthly difference in daily counts between November and June, reflecting over 3 additional hours of sedentary time. Physical activity promotion programs for older persons with chronic conditions need lifestyle physical activity plans adapted to weather extremes.
20871128 How well do patient reports reflect adverse drug reactions reported by rheumatologists? Ag 2011 Jan OBJECTIVE: To analyse the validity of patient reports on adverse drug reactions (ADRs) compared with the reports given by the treating physician. METHODS: Patients with RA enrolled in the German biologics register rheumatoid arthritis observation of biologic therapy (RABBIT) between May 2001 and September 2006 were included in the study. We investigated concordance of reporting and level of agreement between physician- and patient-reported ADRs, taking the physician as gold standard. RESULTS: Data from 4246 patients were analysed. Patients reported on average 1.2 ADRs per patient-year (PY) compared with 0.8 ADRs reported by the physicians (P<0.001). Gastrointestinal disorders were the most frequently reported ADRs by patients (277.8/1000 PYs) and physicians (137.8/1000 PYs), infections were reported with considerably higher frequency by physicians (124/1000 PYs) than by patients (72/1000 PYs). Agreement between patients and physicians (same or similar event reported at the same time) differed according to the nature of the reported ADR. High agreement was found for easily observable, known ADRs (such as alopecia, agreement 76.7%) In contrast, even for some serious ADRs, many patients did not see a connection between the event and the drug taken (e.g. pneumonia, agreement 37.7%). CONCLUSIONS: Patient reports on ADRs are a useful source of information on the safety of new therapies. However, drug surveillance cannot rely on patient reports only, since even life-threatening events were not reported as ADRs by the patients who failed to associate them with the therapy. When coding patient reports on ADRs to a standard coding system, the differences in language and terminology between patients and physicians should be taken into account.
22467927 Heterogeneity of anticitrullinated peptide antibodies and response to anti-tumor necrosis 2012 May OBJECTIVE: To examine fine specificity of anticitrullinated peptide antibodies (ACPA) in relation to responsiveness to anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA). METHODS: Samples from 450 patients with RA treated with anti-TNF agents were analyzed for antibodies to citrullinated α-enolase, vimentin, and fibrinogen peptides. The Disease Activity Score-28 was measured at baseline and 6 months. RESULTS: Both anti-cFib antibodies and the number of citrullinated peptides recognized were associated with a poorer response. These findings were not significant following stratification for anti-cyclic citrullinated peptide 2 antibodies. CONCLUSION: The presence of any ACPA rather than individual ACPA specificities was associated with a poorer response to anti-TNF agents. We suggest that this reflects distinctive differences in the pathogenesis of ACPA-positive and negative RA.