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ID PMID Title PublicationDate abstract
24722018 [System of microcirculation, markers of vascular wall damage and systematicity of the proc 2014 The work was aimed at studying the interrelationship of the microcirculation system and the parameters of endothelial activation with markers of inflammatory process activity in rheumatic diseases (RD). We carried out a comprehensive examination of a total of 330 patients presenting with systemic diseases of connective tissue (SDCT), rheumatoid arthritis (RA) and systemic vasculitis (SV). Studying microcirculation included impregnation of filmy preparations according to the V.V. Kupriyanov technique and biomicroscopy of the conjunctiva of the eyeball. We also determined markers of endothelial activation and lesion of vascular wall, indices of activity of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and vasculitis clinical activity index (VCAI), common carotid artery intima-media thickness (CCA-IMT), biopsy materials of the musculocutaneous flap, of the operational and autopsy materials. Determining the indices of microcirculation showed that first of all the process involves postcapillaries and venules which are dilated, becoming tortuous, with the formation of microaneurysms and stellate venules. Capillaries, postcapillaries and venules were found to contain parietally located small-grained conglomerates of blood platelets and thrombocytic masses plugging up the lumens of microvessels. Intravascular alterations were characterized by the presence of erythrocyte aggregates, stases, microthrombovasculitis, «sludge» phenomenon, and a decrease in capillary blood flow. Extravascular changes included perivascular haemorrhages. In arterioles and precapillaries the inflammatory process manifested itself by swelling, dystrophy and desquamation of endothelial cells, plasmatic impregnation of the walls, luminal thrombosis followed by the development of severe sclerosis and glialinosis. The morphological study showed the presence of destructive alterations in the vascular wall, fibrinoid necrosis, and infiltration-proliferative cellular reaction. The most pronounced changes in the autoimmune inflammation markers had place in RA and systemic lupus erythematosus (SLE). We revealed increased indices of inflammatory process activity such as interleukin-8, C-reactive protein (CRP). We also revealed the signs of endothelial dysfunction, manifesting itself as a statistically significant (p<0.01) increase in concentrations of the soluble vascular cell adhesion molecule (sVCAM-1), von Willebrand factor antigen (VWFA), the number of desquamated endotheliocytes (DE). Also observed was a clear-cut dependence of the level of endothelial activation markers from the degree of the processes activity. We revealed a positive correlation between the level of CRP, IgG RF, the level of sVCAM-1 and the number of DE. The levels of interleukin-8, sVCAM-1 and VWFA were elevated in patients with RD. Increased activity of the disease was accompanied by impairments at the level of the microcirculatory bed, an increase in the concentration of inflammation markers and indices of endothelial dysfunction.
24454473 PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modul 2013 Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.
24252016 Study on the safety and efficacy of tocilizumab, an anti-IL-6 receptor antibody, in patien 2014 May OBJECTIVES: Although treatment of rheumatoid arthritis (RA) has progressed by the use of biologics, amyloid A (AA) amyloidosis is still an intractable complication in patients with RA. In the present study, safety and efficacy of 1-year treatment with an anti-IL-6 receptor antibody tocilizumab (TCZ) on RA and AA amyloidosis were estimated. METHODS: TCZ (8 mg/kg every 4 weeks) was administered to five RA patients complicated with AA amyloidosis. The primary end point was improvement in renal dysfunction and the secondary end point was CDAI at 1 year after the treatment. RESULTS: An improvement in the renal dysfunction, including urinary protein secretion, was found, in four patients including two patients who were refractory to etanercept, with a remarkable decrease of SAA concentration, and the progression of organ dysfunction was prevented at 1 year in all patients treated with TCZ. The mean clinical disease activity index decreased from 33.9 to 4.7 (p = 0.012) in five patients treated with TCZ for 1 year. Three non-serious adverse events were observed in two patients. CONCLUSIONS: TCZ ameliorates renal dysfunction in RA patients complicated with AA amyloidosis who are refractory to conventional therapies, thereby suggesting that TCZ has a potential to regulate AA amyloidosis.
24757131 The epidemiology of rheumatoid arthritis in Ontario, Canada. 2014 Apr OBJECTIVE: Epidemiologic assessments of sufficiently large populations are required in order to obtain robust estimates of disease prevalence and incidence, particularly when exploring the influence of various factors (age, sex, calendar time). We undertook this study to describe the epidemiology of rheumatoid arthritis (RA) over the past 15 years. METHODS: We used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based research database of all Ontarians with RA. The ORAD records were linked with census data to calculate crude and age and sex-standardized prevalence and incidence rates from 1996 to 2010. Vital statistics were used to estimate annual all-cause mortality during the study period. RESULTS: As of 2010, there were 97,499 Ontarians with RA, corresponding to a cumulative prevalence of 0.9%. Age and sex-standardized RA prevalence increased steadily over time from 473 (95% confidence interval [95% CI] 469-478) per 100,000 population (0.49%) in 1996 to 784 (95% CI 779-789) per 100,000 population (0.9%) in 2010. Age and sex-standardized incidence per 100,000 population ranged from 62 (95% CI 60-63) in 1996 to 54 (95% CI 52-55) in 2010. All-cause mortality decreased by a relative 21.4% since 1996. CONCLUSION: Over a 15-year period, we observed an increase in RA prevalence over time. This rise may be attributed to the increasing time to ascertain cases (which may have been latent in the population during earlier years of the study), increasing survival, and/or an increase in the aging background population. Incidence appears to be stable.
24164838 IL-22+ CD4+ T cells in patients with rheumatoid arthritis. 2013 Oct AIM: Interleukin (IL)-22 regulates the pathogenesis of autoimmune diseases. The role of IL-22(+) T-cells in the pathogenesis of rheumatoid arthritis (RA) is unclear. This study aimed at examining the levels of plasma IL-22 and the frequency of IL-22(+) CD4(+) T-cells in patients with RA. METHODS: A total of 30 RA patients and 18 gender- and age-matched healthy controls were recruited. Their peripheral blood mononuclear cells were isolated and stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin for 6 h. The frequency of IL-22(+) , interferon (IFN)-γ(+) and IL-17A(+) CD4(+) T-cells was characterized by flow cytometry. The levels of plasma IFN-γ, IL-17A and IL-22, serum C-reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide antibody (CCP) and erythrocyte sedimentation rate (ESR) were measured. RESULTS: The frequency of IFNγ(-) IL-17A(-)IL-22(+), IFNγ(-)IL-17A(+)IL-22(+), and IFNγ(+) IL-17A(-)IL-22(+) T-cells in CD4(+) T-cells and the levels of plasma IFNγ, IL-17 and IL-22 in RA patients were significant higher than those in healthy controls. The percentages of IL-17A(+)IL-22(+)CD4(+) T-cells were correlated positively with the frequency of Th22 or Th17 cells in the RA patients. The percentages of IL-22(+)CD4(+) T-cells were correlated positively with the values of disease activity score (DAS28) in the RA patients. The percentages of Th22 cells were correlated positively with the levels of plasma IL-22 in the RA patients. CONCLUSION: Our data suggest that IL-22(+)CD4(+) T-cells may contribute to the pathogenesis of RA and that therapeutic targeting of IL-22 may be valuable for the intervention of RA.
24286136 A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early cl 2013 Oct 25 INTRODUCTION: The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA). METHODS: This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (≥ 6/66 swollen and ≥ 8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics. RESULTS: Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70. CONCLUSIONS: Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00771030.
23097311 Immunogenicity, safety, and efficacy of abatacept administered subcutaneously with or with 2013 May OBJECTIVE: To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy. METHODS: This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibody-positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20. RESULTS: Ninety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were -1.67 (95% confidence interval [95% CI] -2.06, -1.28; combination) and -1.94 (95% CI -2.46, -1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were -1.84 (95% CI -2.23, -1.34; combination) and -2.86 (95% CI -3.46, -2.27; monotherapy) at month 18. CONCLUSION: SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.
22915625 Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remis 2013 Jul OBJECTIVE: To compare the performance of the preliminary American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria with the 28-joint count Disease Activity Score (DAS28) remission in unselected 'real-life' patients. METHODS: Remission was calculated according to the DAS28 and to both versions of the ACR/EULAR criteria (Boolean or Simplified Disease Activity Index (SDAI)-based) for 6864 patients with rheumatoid arthritis (RA) who were enrolled in the national database of the German Collaborative Arthritis Centres between 2007 and 2009. Logistic regression analyses identified factors that were responsible for patients in DAS28 remission to miss the new criteria. In addition, the functional status of patients who fulfilled the different remission criteria was compared with that of an age- and sex-matched population sample. RESULTS: Of all patients, 28% were in DAS28, 7% in Boolean and 11% in SDAI remission. Of those in DAS28 remission, 21.0% were also in Boolean and 34% also in SDAI remission. Higher scores for pain and fatigue, the presence of degenerative spine disease, longer disease duration and male gender were significantly associated with missing the new criteria despite being in DAS28 remission. Compared with age- and sex-matched samples from the general population, patients in DAS28 remission had a similar functional ability while patients in remission according to the new criteria had better functional scores. CONCLUSIONS: Patients fulfilling the new remission criteria tend to be not only free from active RA, but also from other disabling diseases. If these criteria are applied in clinical practice to guide treatment decisions, the impact of comorbidity should be taken into account.
24448681 Ultrasound evaluation of greater trochanter pain syndrome in patients with spondyloarthrit 2014 Jul Although greater trochanter pain syndrome (GTPS) is a prevalent cause of musculoskeletal pain in the general population, there is lack of imaging studies searching for differential features of inflammatory enthesitis in GTPS. We analyzed the features of GTPS using sonography and magnetic resonance imaging (MRI) to identify useful differential signs between spondyloarthritis (SpA) and other inflammatory or non-inflammatory musculoskeletal diseases. All patients with unilateral GTPS attended by our Arthritis Unit between February 2011 and March 2012 were included. Patients were classified as having SpA or mechanical (without inflammatory musculoskeletal disease) GTPS. Rheumatoid arthritis (RA) patients were also included as inflammatory controls. Ultrasound scans of the painful and contralateral, asymptomatic, greater trochanter were made. We assessed the gluteus medius and gluteus minimus tendons for signs suggestive of tendinopathy. Random MRI of the same regions was made in a subgroup of patients to validate the ultrasound findings. A total of 107 patients with unilateral GTPS were included, of whom 96 were female, with a mean age of 61.6 years: 34 had SpA, 48 had non-inflammatory musculoskeletal disease, and 25 had RA. No specific sonographic features for SpA were found. Pathological findings were more frequent in patients without musculoskeletal inflammatory disease (mainly bursitis and erosions). A large number of alterations were found in the asymptomatic side (around 40 % had cortical irregularities and 20 % bursa effusion). Signs of enthesopathy were more prevalent in the gluteus minimus tendon, regardless of the diagnosis (54.2 % had erosions, 39.3 % bursitis, 38.3 % calcifications and 37.4 % tendinosis). No patient had power Doppler signal. Age was the main factor in the appearance of tendinopathy. MRI confirmed the changes detected by ultrasound in all 40 patients evaluated. GTPS in patients with SpA has similar sonographic findings to those observed in patients with RA and patients without musculoskeletal inflammatory disease. Neither sonography nor MRI was clinically useful in classifying GTPS as a manifestation of SpA.
23703486 [Prevalence of selected musculoskeletal conditions in Germany: results of the German Healt 2013 May The term musculoskeletal condition (MSKC) comprises inflammatory and degenerative diseases of joints and bones. They are among the most common conditions in older age and cause of severe long-term pain, physical disability, and decrease in quality of life. Data from the German Health Interview and Examination Survey for Adults (DEGS1) were used to estimate the life-time prevalence of osteoarthritis, rheumatoid arthritis (RA) and osteoporosis in Germany. A total of 7,988 persons aged 18-79 years (osteoporosis 50-79 years) were asked to report doctor-diagnosed MSKC in face-to-face interviews. Women were more likely to report all MSKC and all prevalences increase with age. Osteoarthritis is reported by 22.3 % of women and 18.1 % of men, RA by 3.2 % of women and 1.9 % of men, and osteoporosis by 13.1 % of women and 3.2 % of men. MSKC are of great relevance for older adults in Germany. Data from DEGS1 provide a lot of information along to MSKC and hereby allow a closer description of the health situation of older adults. An English full-text version of this article is available at SpringerLink as supplemental.
24706412 Moving the injectable methotrexate service closer to home: a practice development initiati 2014 Sep OBJECTIVE: The aim of this practice development project was to make it quicker and easier for patients to switch to subcutaneous (s/c) methotrexate and thereby introduce a nurse-led methotrexate clinic into a district general hospital, which would make the best use of the advanced knowledge and skills of the rheumatology specialist nurses; empower patients and improve their experience; and introduce cost savings for the Trust. METHODS: Over a period of four months, meetings were held with pharmacists, clinicians, administrative and support staff to formulate a plan to introduce the changes and agree the benefits to patients. A detailed plan for the practice development project addressed the procedures to follow, the safety issues for patients and the revision of current documentation. RESULTS: A review of service in the year before and after the change revealed that the number of rheumatoid arthritis patients who had switched to s/c methotrexate had increased by 80%. This was a significant difference (p = 0.049), which strongly suggested that the change in service was the reason for the increased number of patients who were able to switch their route of administration of methotrexate. CONCLUSION: This project demonstrated that not only do nurse specialists have the skills to make clinical decisions and judgements, prescribe medications and escalate therapies with no detriment to the patients, but also that this practice can lead to a more efficient and effective service, at a reduced cost to the Trust.
23681398 Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment. 2013 Sep OBJECTIVE: Glycosylation is the most common post-translational modification and is altered in disease. The typical glycosylation change in patients with inflammatory arthritis (IA) is a decrease in galactosylation levels on IgG. The aim of this study is to evaluate the effect of anti-TNF therapy on whole serum glycosylation from IA patients and determine whether these alterations in the glycome change upon treatment of the disease. METHODS: Serum samples were collected from 54 IA patients before treatment and at 1 and 12 months after commencing anti-TNF therapy. N-linked glycans from whole serum samples were analysed using a high-throughput hydrophilic interaction liquid chromatography-based method. RESULTS: Glycosylation on the serum proteins of IA patients changed significantly with anti-TNF treatment. We observed an increase in galactosylated glycans from IgG, also an increase in core-fucosylated biantennary galactosylated glycans and a decrease in sialylated triantennary glycans with and without outer arm fucose. This increase in galactosylated IgG glycans suggests a reversing of the N-glycome towards normal healthy profiles. These changes are strongly correlated with decreasing CRP, suggesting a link between glycosylation changes and decreases in inflammatory processes. CONCLUSION: Glycosylation changes in the serum of IA patients on anti-TNF therapy are strongly associated with a decrease in inflammatory processes and reflect the effect of anti-TNF on the immune system.
25244314 Receipt of glucocorticoid monotherapy among Medicare beneficiaries with rheumatoid arthrit 2014 Oct OBJECTIVE: Using disease-modifying antirheumatic drugs (DMARDs) improves outcomes in rheumatoid arthritis (RA) and is a nationally endorsed quality measure. We investigated the prevalence and predictors of receiving glucocorticoids alone for the treatment of RA in a nationwide sample of Medicare beneficiaries. METHODS: Among individuals ages ≥65 years with RA enrolled in the Part D prescription drug benefit in 2009, we compared those with ≥1 DMARD claim to those receiving glucocorticoid monotherapy, defined as no DMARD claim and an annual glucocorticoid supply of ≥180 days or an annual dose of ≥900 mg of prednisone or equivalent. We fit multivariable models to determine the sociodemographic and clinical factors associated with glucocorticoid monotherapy. RESULTS: Of 8,125 beneficiaries treated for RA, 10.2% (n = 825) received glucocorticoids alone. Beneficiaries with low incomes were more likely to receive glucocorticoids alone (12.3%; 95% confidence interval [95% CI] 10.9-13.8% versus 9.4%; 95% CI 8.6-10.1%), as were those living in certain US regions. More physician office visits and hospitalizations were associated with glucocorticoid monotherapy. Individuals who had no contact with a rheumatologist were significantly more likely to receive glucocorticoids alone (17.5%; 95% CI 16.0-19.0% versus 8.5%; 95% CI 7.4-9.5% for those with no rheumatology visits versus 1-4 visits). CONCLUSION: Approximately 1 in 10 Medicare beneficiaries treated for RA received glucocorticoids without DMARDs in 2009. Compared to DMARD users, glucocorticoid users were older, had lower incomes, were more likely to live in certain US regions, and were less likely to have seen a rheumatologist, suggesting persistent gaps in quality of care despite expanded drug coverage under Part D.
24800496 [Evaluation of cut-off value for autoantibodies against double-stranded DNA-complexed nucl 2014 Mar The new classification criteria for systemic lupus erythematosus (SLE) by Systemic Lupus International Collaborating Clinics (SLICC) published in 2012 have defined positive level titer of antibody against double stranded (ds) DNA as more than double the reference range if tested by enzyme linked immunosorbent assay (ELISA). The aim of this study was to evaluate optimal cut-off value and diagnostic performance of the anti-dsDNA nucleosome-complexed (anti-dsDNA-NcX) ELISA, which uses salmon testis DNA complexed with purified nucleosomes as antigens, for diagnosis of SLE. Titers of antibodies against dsDNA-complexed nucleosome were measured in sera of 76 patients with SLE, 148 with other connective tissue diseases, and 323 healthy volunteers. Sensitivity, specificity, correlation and concordance rate were compared among anti-dsDNA-NcX, conventional ELISA methods (EIA) and radioimmunoassay (RIA). As a results, concordance rates and Spearman's coefficient of rank correlation (r(s)) of anti-dsDNA-NcX with EIA and RIA were 59.2%, r(s) = 0.40 and 53.9%, r(s) = 0.21, respectively. Receiver operating characteristic curve analysis showed that the titer of 44 IU/mL calculated as 99 percentile of 323 healthy volunteers is a better cut-off value for anti-dsDNA-NcX than the 100 IU/mL recommended by the manufacturer. By setting the cut-off value at 44 IU/mL, anti-dsDNA-NcX showed the highest sensitivity (75.0%) and specificity (90.5%) of the 3 assays. With SLICC criterion, positivity rates of anti-dsDNA-NcX, EIA and RIA for SLE patients were 50.0%, 30.3% and 50.0%, respectively. In conclusion, anti-dsDNA-NcX has a good diagnostic performance for SLE with our proposed cut-off value of 44 IU/mL.
24286474 Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk 2013 Oct 23 INTRODUCTION: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. METHODS: We identified 192 women in the Nurses' Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom BioPlex platform. We used conditional logistic regression to calculate the relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive and examined RRs by time between blood draw and RA onset. Measures of multiplicative and additive interaction between any ACPA-positive and HLA-SE were calculated. RESULTS: All ACPAs by peptide groups were significantly associated with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA varied over time with the strongest association in those with blood draw less than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA-SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases showed reactivity to more ACPA types than HLA-SE negative (χ2 test for trend, P = 0.01). CONCLUSIONS: There is increasing ACPA reactivity up to 10 years before RA onset with the strongest association within 5 years of RA onset. The magnitude of the response to ACPAs, in combination with the presence of HLA-SE, is most important for identifying those individuals with the highest risk of RA.
25060516 Meta-analysis of functional MBL polymorphisms. Associations with rheumatoid arthritis and 2014 Sep OBJECTIVE: The aim of this study was to determine whether functional mannose-binding lectin gene (MBL) polymorphisms are associated with the susceptibility to rheumatoid arthritis (RA) or primary Sjögren's syndrome (pSS). METHODS: A meta-analysis was conducted to investigate the potential association of RA or pSS with MBL polymorphisms, including the codon 54 (allele B), codon 57 (allele C), and codon 52 (allele D) variants of exon 1, and the - 550 (allele L) and - 221 (allele X) promoter variants. RESULTS: A total of 12 comparative studies, including eight RA (1623 patients and 1671 controls) and four pSS (280 patients and 516 controls) studies, were included in the meta-analysis. The meta-analysis revealed no association between the MBL B allele and RA in the overall study population (odds ratio [OR] 0.991, 95 % confidence interval [CI] 0.726-1.355, p = 0.957). However, the meta-analysis showed significant associations between the MBL D, H, and X alleles and RA in the overall population (OR 1.708, 95 % CI 1.077-2.707, p = 0.023; OR 1.936, 95 % CI 1.218-3.078, p = 0.005; OR 1.582, 95 % CI 1.216-2.057, p = 0.001, respectively). An association was found between the MBL B allele and pSS in the overall study population (OR 0.691, 95 % CI 0.541-0.917, p = 0.010). Stratification by ethnicity indicated a trend toward an association between the B allele and pSS in European populations, but no association in Asian populations (OR 0.689, 95 % CI 0.465-1.021, p = 0.063; OR 0.896, 95 % CI 0.311-2.562, p = 0.838, respectively). CONCLUSION: This meta-analysis demonstrated an association between the MBL D, L, and X alleles and the risk of RA. It also demonstrated an association between the MBL B allele and the susceptibility to pSS, suggesting a protective role of the MBL B allele against the development of pSS.
25365108 NOR-DMARD data management: implementation of data capture from electronic health records. 2014 Sep OBJECTIVES: The use of electronic health records (EHR) is an essential part of modern health care, and electronic data capture (EDC) has become essential for managing clinical trials. Usually, these two entities are independent of each other, and transfer from one system to another is done manually. Our aim was to develop a method to capture data directly from the EHR system and transfer them into an EDC system for the NORwegian Disease-Modifying Anti-Rheumatic Drugs (NOR-DMARD) registry. METHODS: All rheumatology departments contributing to NOR-DMARD had implemented a structured EHR system. Data are extracted locally and securely transferred to the study data management once a month. The study data management then parse the data into a readable format for the EDC and import the data. Once the data is in the EDC, they are available to all authorized researchers and downloadable in a preferred format. RESULTS: From May 2012 to August 2014 almost 6400 visits in 3400 patients treated with biologics have been successfully registered in the EDC system. Previously, NOR-DMARD used standard paper-based case report forms (CRFs), with a substantial cost for data entry. Setting up and maintaining the EDC system required some investments, but the amount saved from avoiding paper handling has made the shift into EDC profitable. In addition to this, gains have been made in administration and data quality. CONCLUSIONS: The transition from paper and pencil format to a fully electronic data management system in NOR-DMARD has had obvious advantages regarding feasibility, cost, data quality and accessibility of the data.
23830828 Outcome of surgery for rheumatoid cervical spine at one institute over three decades. 2013 Nov BACKGROUND CONTEXT: Surgical intervention is a therapeutic choice for atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) associated with rheumatoid cervical spine. However, the long-term outcomes of different subgroups remain unclear, although rheumatoid arthritis (RA) is a progressive disease even after surgery. PURPOSE: To evaluate the outcomes of surgery for various subgroups of rheumatoid cervical spine, performed at a single institute over three decades. STUDY DESIGN: Retrospective clinical analysis. PATIENT SAMPLE: One-hundred eighteen seropositive RA patients treated at one institute over the past three decades. Atlantoaxial fixation was performed in 28 AAS patients. Occipitospinal fusion was performed in 41 irreducible AAS or VS patients. Laminotomy with autologous bone fusion was performed in 22 patients, anterior fusion in 5, laminoplasty in 4, and posterior decompression/fusion with instrumentation in 12 with SAS. METHODS: Clinical outcomes using the Japanese Orthopedic Association score, complications, deterioration of RA, and mortality rate during the follow-up were investigated from preoperation to more than 10 years after surgery in the subgroups. OUTCOME MEASURES: Outcomes were compared among the subgroups. RESULTS: Patients with AAS exhibited significantly better clinical outcomes throughout the follow-up period compared with patients from the other subgroups. Patients with SAS had the worst neurologic status even at preoperation, and the symptomatic improvement achieved by surgery deteriorated within less than 5 years. Deterioration of outcome was caused by occurrence of complications and deterioration of RA during the follow-up. The mortality rates at 5 and 10 years after surgery were 20% and 33%, respectively. CONCLUSIONS: The outcome of surgery for rheumatoid cervical spine was different in the various subgroups and associated with the occurrence of complications and deterioration of RA.
22825303 Quantification of IFNγ- and IL17-producing cells after stimulation with citrullinated pro 2013 Oct Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA) and are currently used as a diagnostic marker. In this study, we wanted to quantify the numbers of T cells that react to a wide range of citrullinated proteins in a wide range of HLA-DR subtypes in order to investigate whether citrullination might create T-cell neo-epitopes and could initiate a universal T-cell response. Therefore, PBMCs from healthy volunteers and RA patients were stimulated with a citrullinated and non-citrullinated cell extract on IFNγ-ELISpot. We found a significantly higher number of IFNγ-secreting cells after stimulation with citrullinated proteins compared to non-citrullinated proteins in RA patients (1:14,441 cells vs. 1:32,880 cells) as well as in healthy subjects (1:6,261 reactive cells compared to 1:16,212 cells). Additionally, a higher number of IL17-secreting cells were found after stimulation with citrullinated proteins compared to their non-citrullinated counterparts. Our data indicate that citrulline-dependent T-cell response is not restricted to RA patients but that citrullination as such gives rise to a universal break in tolerance.
23987246 Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood fro 2014 OBJECTIVES: Although methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA), patients experience clinical resistance to MTX upon prolonged treatment. We explored whether new-generation antifolates elicit superior anti-inflammatory properties when compared to MTX, based on their capacity to inhibit tumour necrosis factor (TNF)-α production. METHOD: T cells in whole blood from 18 RA patients (including MTX-naïve, MTX- responsive, and MTX non-responsive patients) and seven healthy volunteers were stimulated with αCD3/αCD28 antibodies and incubated ex vivo for 72 h with MTX and eight novel antifolate drugs with potentially favourable biochemical and pharmacological properties. Drug concentrations exerting 50% inhibition (IC-50) of TNF-α production (by enzyme-linked immunosorbent assay, ELISA) were determined as an estimate for their anti-inflammatory capacity. In addition, induction of T-cell apoptosis was evaluated by flow cytometry. RESULTS: The new-generation antifolates PT523, PT644, raltitrexed, and GW1843 proved to be potent inhibitors of TNF-α production in activated T cells from all three groups of RA patients and from healthy volunteers. Based on IC-50 values, these antifolates were up to 10.3 times more potent than MTX. The anti-inflammatory effects were observed at drug concentrations that provoked suppression of T-cell activation and induction of apoptosis in 20-40% of activated T cells. CONCLUSION: In an ex-vivo setting, novel antifolates elicited marked inhibition of TNF-α production in activated T cells from RA patients. Further clinical evaluation is warranted to investigate whether a low dosage of these antifolates can elicit immunosuppressive effects equivalent to MTX, and whether they are superior to MTX in patients who fail to respond to MTX.