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ID PMID Title PublicationDate abstract
26567181 Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious 2016 Sep OBJECTIVE: This observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis. METHODS: We investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (≤30 days), and (3) death after SI without known sepsis (≤90 days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously. RESULTS: Sepsis within 30 days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90 days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk. CONCLUSIONS: These results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.
27784339 Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice followin 2016 Oct 26 BACKGROUND: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. METHODS: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. RESULTS: Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. CONCLUSIONS: Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present.
26811171 Process Evaluation of a Workplace Integrated Care Intervention for Workers with Rheumatoid 2016 Sep Purpose To perform a process evaluation of the implementation of a workplace integrated care intervention for workers with rheumatoid arthritis to maintain and improve work productivity. The intervention consisted of integrated care and a participatory workplace intervention with the aim to make adaptations at the workplace. Methods The implementation of the workplace integrated care intervention was evaluated with the framework of Linnan and Steckler. We used the concepts recruitment, reach, dose delivered, dose received, fidelity and satisfaction with the intervention. Data collection occurred through patient questionnaires and medical records. Results Participants were recruited by sending a letter including a reply card from their own rheumatologist. In total, we invited 1973 patients to participate. We received 1184 reply cards, and of these, 150 patients eventually participated in the study. Integrated care was delivered according to protocol for 46.7 %, while the participatory workplace intervention was delivered for 80.6 %. Dose received was nearly 70 %, which means that participants implemented 70 % of the workplace adaptations proposed during the participatory workplace intervention. The fidelity score for both integrated care and the participatory workplace intervention was sufficient, although communication between members of the multidisciplinary team was limited. Participants were generally satisfied with the intervention. Conclusions This process evaluation shows that our intervention was not entirely implemented as intended. The integrated care was not delivered to enough participants, but for the intervention components that were delivered, the fidelity was good. Communication between members of the multidisciplinary team was limited. However, the participatory workplace intervention was implemented successfully, and participants indicated that they were satisfied with the intervention.
26087258 Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthrit 2015 Jun 16 Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than -16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications.
25865349 Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using 2017 Mar AIM: The objectives of this study were: (i) to develop a standardized method of quantifying bone mineral density (BMD) and microarchitecture in the hand and wrist bones of patients with rheumatoid arthritis (RA) using high resolution- peripheral quantitative computed tomography (HR-pQCT); (ii) to compare quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP) subjects; and (iii) to correlate quantitative bone parameters at the distal radius with those at the metacarpal heads in RA subjects. METHODS: HR-pQCT imaging of the dominant hand and wrist was performed in 12 female RA patients. BMD and trabecular parameters for the 2-12% head region of the second and third metacarpals were calculated and compared between RA patients and healthy controls. Bone parameters were also calculated for 110 slices of the distal radius in RA patients and compared to data from controls and PM-OP women from a previous study. RESULTS: Compared to controls, RA patients had significantly decreased BMD, trabecular volume and number, and increased trabecular heterogeneity in the third metacarpal and distal radius. Significantly lower trabecular number and significantly higher ratio of outer annular trabecular BMD to inner trabecular BMD were observed in patients with RA, compared to patients with osteopenia (P < 0.05). Trabecular BMD in the third metacarpal and in the distal radius were significantly correlated (ρ = 0.918, P < 0.0001) in RA patients. CONCLUSION: This study established a standardized method for quantifying bone density and trabecular properties in the hand and wrist bones of RA patients using HR-pQCT. Deterioration of bone structure in RA patients was found comparable to that in osteopenic women, and trabecular bone loss near affected joints was found to be correlated with bone loss away from joints.
25302697 Rheumatoid arthritis is associated with higher ninety-day hospital readmission rates compa 2015 May OBJECTIVE: To examine whether an underlying diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA) impacts the 90-day readmission rates after total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: We analyzed prospectively collected data from an integrated health care system, Total Joint Replacement Registry, of adults with RA or OA undergoing unilateral primary THA or TKA during 2009-2011. Adjusted logistic regression models for 90-day readmission were fit. Odds ratios with 95% confidence intervals (95% CIs) were calculated. Study year was an effect modifier for the outcome; therefore separate analyses were conducted for each of the 3 study years. RESULTS: Of the 34,311 patients, 496 had RA and 33,815 had OA. Comparisons of RA and OA patients, respectively, were 73% and 61% women, 45% and 70% white, and patients had a mean age of 61 versus 67 years (P < 0.001). Crude 90-day readmission rates for RA and OA were 8.5% and 6.7%, respectively. The adjusted odds of 90-day readmission increased from year to year for RA compared to OA patients, from 0.89 (95% CI 0.46-1.71) in 2009 to 1.34 (95% CI 0.69-2.61) in 2010, and to 1.74 (95% CI 1.16-2.60) in 2011. The 2 most common readmission reasons were joint prosthesis infection (10.2%) and septicemia (10.2%) in RA and joint prosthesis infection (5.7%) and other postoperative infection (5.1%) in OA. CONCLUSION: RA is a risk factor for 90-day readmission after primary THA or TKA. An increasing risk of readmissions noted in RA in 2011 is concerning and indicates that further studies should examine the reasons for this increasing trend.
25887268 SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice. 2015 Jun Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that affects about 1% of the population worldwide. RA is mainly manifested by persistent synovitis and progressive joint destruction. The aim of the present study was to examine the anti-arthritis effects of SND-117, a sinomenine bivalent that is obtained from the structure modification of a clinically available anti-RA drug, sinomenine. The arthritis model (CIA) was established by immunizing DBA/1 mice with type II collagen, and the arthritis scores including inflammation, joint destruction and bone erosion were assessed after booster immunization for 3weeks. The levels of cytokines such as IL-1β, IL-6 and TNF-α were analyzed by quantitative PCR and ELISA. The TNF-α induced NF-κB activation in fibroblast-like synovial cells (FLSCs) was analyzed by Western blot. SND-117 significantly relieved the inflammatory symptoms of collagen-induced arthritis, reduced bone erosion and joint destruction in CIA mice. The serum levels of IL-1β, IL-6 and TNF-α of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-κB p65 in FLSCs upon TNF-α stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-κB signaling, and might provide potential clinic benefits in rheumatoid arthritis management.
28032180 Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study. 2017 Apr The aim of this study was to investigate (a) the mortality in a clinical cohort of patients with established rheumatoid arthritis in comparison with the general Dutch population over 15 years, (b) the trend in the mortality ratio during the study period, and (c) causes of death and compare these with the general population. In 1997, a sample of 1222 patients was randomly selected from the register of a large rheumatology outpatient clinic. Their mortality and primary causes of death between 1997 and 2012 were obtained from Statistics Netherlands. The standardized mortality ratio (SMR) for all-cause mortality and the number of life-years lost in the study period, adjusted for age, sex, and calendar year, were calculated. A linear poisson regression analysis was performed to evaluate change in all-cause SMR over time. Finally, the SMRs for cause-specific mortality were calculated. The mean age of the population at baseline was 60.4 (SD 15.4) years, and 72.6% of the patients were women. The estimated SMR (95% CI) for all-cause mortality was 1.54 (1.41, 1.67) with about one life-year lost over the study period. There was a trend to decreasing SMR (2% annually, p = .07). Mortality was higher compared with the general population for circulatory system diseases, respiratory system diseases, musculoskeletal system diseases, and digestive system diseases (p < .05). The observed mortality among patients with RA was 54% higher than in the general population after adjustment for age, sex and calendar year. More than one life-year was lost over 15 years, and the mortality tended to decrease over time. The mortality was higher for cardiovascular, respiratory, musculoskeletal and digestive diseases.
27393079 A descriptive, cross-sectional study characterizing bone erosions in rheumatoid arthritis 2016 Sep The aim of this study is to characterize bone erosions in metatarsal heads (MTH) in rheumatoid arthritis (RA) and gout by grayscale ultrasound. In a descriptive, cross-sectional study, we evaluated 40 patients with RA and 40 with gout, both diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria, respectively. All patients had bone erosion demonstrated by ultrasound, which was used, following OMERACT criteria, to describe the shape, size, number, border definition, overhanging margin, topography (intra- or extra-articular), and distribution (over dorsal, medial, lateral, or plantar aspect) of the lesions in the MTH. Descriptive statistics were used and a concordance exercise between two ultrasonographers blinded to the diagnosis was performed. Bone erosions in RA were observed most frequently at the plantar and lateral aspect of the fifth MTH, round in 96 %, small-sized (2.43 ± 0.9 mm), intra-articular (100 %), and single (75 %). Few bone erosions had a well-defined border an overhanging margin while in gout were found most frequently in the medial and dorsal aspect of the first MTH, single in 71 %, intra-articular in 100 %, and of median size (4.0 ± 2.3). For shape, 51 % was round and 49 % was oval. A well-defined border was present in 39 %, and an overhanging margin in 62 %. Inter-rater reliability kappa was excellent (0.81, 95 % CI 0.56-1.00). Some characteristics of bone erosions in RA, including shape, size, ill-defined border, and localization in the fifth MTH could distinguish the lesions from gout. Grayscale US has excellent reliability to describe bone erosions in RA and gout.
24854355 Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced 2015 Oct OBJECTIVE: Skeletal muscle weakness is a prominent clinical feature in patients with rheumatoid arthritis (RA), but the underlying mechanism(s) is unknown. Here we investigate the mechanisms behind arthritis-induced skeletal muscle weakness with special focus on the role of nitrosative stress on intracellular Ca(2+) handling and specific force production. METHODS: Nitric oxide synthase (NOS) expression, degree of nitrosative stress and composition of the major intracellular Ca(2+) release channel (ryanodine receptor 1, RyR1) complex were measured in muscle. Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]i) and force production were assessed in single-muscle fibres and isolated myofibrils using atomic force cantilevers. RESULTS: The total neuronal NOS (nNOS) levels were increased in muscles both from collagen-induced arthritis (CIA) mice and patients with RA. The nNOS associated with RyR1 was increased and accompanied by increased [Ca(2+)]i during contractions of muscles from CIA mice. A marker of peroxynitrite-derived nitrosative stress (3-nitrotyrosine, 3-NT) was increased on the RyR1 complex and on actin of muscles from CIA mice. Despite increased [Ca(2+)]i, individual CIA muscle fibres were weaker than in healthy controls, that is, force per cross-sectional area was decreased. Furthermore, force and kinetics were impaired in CIA myofibrils, hence actin and myosin showed decreased ability to interact, which could be a result of increased 3-NT content on actin. CONCLUSIONS: Arthritis-induced muscle weakness is linked to nitrosative modifications of the RyR1 protein complex and actin, which are driven by increased nNOS associated with RyR1 and progressively increasing Ca(2+) activation.
26984091 Thrombocytopenia and Anemia with Anti-c-Mpl antibodies Effectively Treated with Cyclospori 2016 A 61-year-old woman with rheumatoid arthritis who was undergoing hemodialysis for end-stage renal failure was transferred to our hospital due to severe thrombocytopenia and anemia. A bone marrow biopsy showed the complete absence of megakaryocytes and erythroblasts. Cyclosporine treatment resulted in the improvement of her megakaryocyte and erythroblast levels, and a decrease in her serum level of anti-c-Mpl (thrombopoietin receptor) antibodies. After this initial improvement, her anemia progressively worsened, despite the continuous administration of immunosuppressive therapy with cyclosporine. Her platelet and leukocyte counts remained stable. This is the first report of a probable case of anti-c-Mpl antibody-associated pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura.
25227901 Clinical trials documenting the efficacy of low-dose glucocorticoids in rheumatoid arthrit 2015 Twelve clinical trials have documented that prednisone or prednisolone in doses of 10 mg/day or less is efficacious to improve function, maintain status and/or slow radiographic progression in patients with rheumatoid arthritis (RA). An early trial reported by de Andrade et al. [Ann Rheum Dis 1964;23:158-162] in 1964 indicated that 5 mg of prednisolone at night was preferred to 5 mg of prednisone in the morning. Harris et al. [J Rheumatol 1983;10:713-721] documented the efficacy of 5 mg/day of prednisone in a non-double-blind trial in 1983. Two important trials in the 1990s by Kirwan [N Engl J Med 1995;333:142-146] using 7.5 mg/day, and the COBRA study by Boers et al. [Lancet 1997;350:309-318] with step-down from 60 mg rapidly tapered to 5 mg/day led to strong advocacy of low-dose glucocorticoids. In 2002, the first Utrecht Study [Ann Intern Med 2002;136:1-12] indicated that 10 mg/day prednisone slowed radiographic progression, a finding confirmed and extended in 2005 by Svensson et al. [Arthritis Rheum 2005;52:3360-3370] with 7.5 mg/day, and Wassenberg et al. [Arthritis Rheum 2005;52:3371-3380] with 5 mg/day of prednisolone. In 2008, Buttgereit et al. [Lancet 2008;371:205-214] reported CAPRA-1, which documented that modified-release prednisone or prednisolone taken at bedtime led to lower morning stiffness and IL-6 levels compared to usual morning prednisone. In 2009, Pincus et al. [Ann Rheum Dis 2009;68:1715-1720] reported a withdrawal clinical trial, in which patients who took 3 mg/day were gradually withdrawn to placebo, and dropped out at a significantly higher rate than control patients who were 'withdrawn' to prednisone. In 2012, a second Utrecht Study [Ann Intern Med 2012;156:329-339], CAMERA-II, documented that 10 mg of prednisone added to a 'treat-to-target' strategy with methotrexate provided incremental slowing of radiographic progression. An Italian study of patients with early RA who received step-up disease-modifying antirheumatic drug therapy over 2 years plus prednisolone or not indicated higher rates of clinical remission and sustained remission associated with 7.5 mg/day of prednisolone [Arthritis Res Ther 2012; 14:R112]. The CAPRA-2 trial [Ann Rheum Dis 2013;72:204-210] documented that modified-release nighttime prednisone or prednisolone was significantly more efficacious than placebo. Taken together, these 12 clinical trials indicate that low-dose glucocorticoids prednisone or prednisolone provides symptomatic relief, improved functional status and slowing of radiographic progression for patients with RA. © 2014 S. Karger AG, Basel.
26219489 Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center observational c 2015 Oct Inhibitors of tumor necrosing factor alpha (TNF-a) have proven to be highly effective in the treatment of rheumatoid arthritis (RA). Concerns, however, are raised about the possible association between these treatments and an increased development of malignancies. The objective of this paper was to compare the risk of hematologic and solid malignancies in patients treated for RA with anti-TNF therapy, with the risk in the general population. From January 2000 until January 2012, all RA patients that started treatment with anti-TNF agents were included in this single-center cohort study. The primary outcome of this study was the incidence of malignancy after starting anti-TNF treatment. In our cohort of 365 patients, 34 malignancies were discovered in 30 patients after the start of anti-TNF treatment; 20 patients developed a solid malignancy, 6 a hematologic, 2 a solid and a hematologic malignancy, and 2 patients developed 2 solid malignancies. The overall incidence rate (IR) of malignancy was 1379.1 per 100.000 patient years. The risk or standardized incidence ratio (SIR) of solid malignancy, calculated by comparison with the age-adjusted population in Flanders, was 120.1 in female and 136.7 in male patients. The calculated SIR of hematologic malignancy was 450.8 for women and 473.9 for men. Some immune modulation-related lymphoproliferative disorders regressed spontaneously when stopping TNF blockers. Overall, the malignancy risk in our rheumatoid arthritis patients treated with anti-TNF therapy was slightly higher than in the normal population; the risk of hematologic malignancies was more important.
27560702 Pulmonary pharmacodynamics of an anti-GM-CSFRα antibody enables therapeutic dosing that l 2016 Oct Pulmonary alveolar proteinosis is associated with impaired alveolar macrophage differentiation due to genetic defects in the granulocyte macrophage colony-stimulating factor (GM-CSF) axis or autoantibody blockade of GM-CSF. The anti-GM-CSFRα antibody mavrilimumab has shown clinical benefit in patients with rheumatoid arthritis, but with no accompanying pulmonary pathology observed to date. We aimed to model systemic versus pulmonary pharmacodynamics of an anti-GM-CSFRα antibody to understand the pharmacology that contributes to this therapeutic margin. Mice were dosed intraperitoneal with anti-GM-CSFRα antibody, and pharmacodynamics bioassays for GM-CSFRα inhibition performed on blood and bronchoalveolar lavage (BAL) cells to quantify coverage in the circulation and lung, respectively. A single dose of 3 mg/kg of the anti-GM-CSFRα antibody saturated the systemic cellular pool, but dosing up to 10 times higher had no effect on the responsiveness of BAL cells to GM-CSF. Continued administration of this dose of anti-GM-CSFRα antibody for 7 consecutive days also had no inhibitory effect on these cells. Partial inhibition of GM-CSFRα function on cells from the BAL was only observed after dosing for 5 or 7 consecutive days at 30 mg/kg, 10-fold higher than the proposed therapeutic dose. In conclusion, dosing with anti-GM-CSFRα antibody using regimes that saturate circulating cells, and have been shown to be efficacious in inflammatory arthritis models, did not lead to complete blockade of the alveolar macrophages response to GM-CSF. This suggests a significant therapeutic window is possible with GM-CSF axis inhibition.
26609697 Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early R 2016 Apr BACKGROUND: Recent consensus emphasizes the importance of studying individuals at risk for rheumatoid arthritis (pre-RA) and those with early RA (eRA). Periodontal tissues have been recently evaluated, but these studies are limited. To evaluate the periodontal condition, immunoglobulin (Ig)G subclasses against Porphyromonas gingivalis in individuals with pre-RA and eRA were compared with controls to establish an association between periodontal infection markers and rheumatic activity. METHODS: Rheumatologic and periodontal condition was evaluated in 119 individuals with pre-RA, 48 patients with eRA, and matched controls. P. gingivalis IgG1 and IgG2 were analyzed. C-reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor, anticitrullinated protein antibodies (ACPAs), and RA activity were measured. The groups were compared with McNemar test and paired t-test. Conditional logistic regression was performed for pre-RA confounders, and χ(2) test was used to evaluate periodontal variables and RA activity indices. RESULTS: Pre-RA individuals showed significantly higher levels of plaque index (P = 0.01) and bleeding on probing (P = 0.03) and higher severity of periodontal disease (P = 0.02). Periodontitis was associated with pre-RA (odds ratio, 3.39; 95% confidence interval, 1.64 to 7.01) but not with eRA. In pre-RA, P. gingivalis-specific IgG2 was associated with ACPAs (P = 0.049) and disease severity visual analog scale (P = 0.03). In eRA, IgG2 against P. gingivalis was associated with ESR (P = 0.046) and ACPAs (P = 0.04). P. gingivalis was associated with ACPAs (P = 0.04). CONCLUSIONS: This study shows that individuals with pre-RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre-RA and markers of RA activity in individuals with eRA.
25615002 Quality process measures for rheumatoid arthritis: performance from members enrolled in a 2015 Feb BACKGROUND: Health care quality problems are reflected in the underuse, overuse, and misuse of health care services. There is evidence suggesting that the quality of rheumatoid arthritis (RA) patient care is suboptimal, which has spurred the development of a number of systematic quality improvement metrics. OBJECTIVE: To investigate a quality process measurement set in a sample of commercially insured RA patients. METHODS: Medical, pharmacy, and laboratory claims for members with an RA diagnosis (ICD-9-CM 714.x) during calendar years 2008 through 2012 were extracted from the Optum Clinformatics Data Mart database. Eight process quality measures focused on RA patient response and tolerance to therapy were examined in the claims database. Measures were calculated for individual calendar years from 2009 to 2012, inclusive. RESULTS: The majority of adult RA patients received at least 1 prescription for a disease-modifying antirheumatic drug (DMARD) across the 4 measurement years: range = 78.5%-81.6%. Erythrocyte sedimentation rate and C-reactive protein testing were also evident in the majority of the sample, with 67.1%-72.2% of newly diagnosed RA patients receiving baseline testing, and 56.0%-58.7% of existing RA patients receiving annual testing. Among methotrexate users, liver function tests were performed in 74.5%-75.7% of treated patients, serum creatinine tests in 70.1%-72.6% of patients, and complete blood count tests in 74.5%-76.0% of patients. Additionally, most patients initiating a new DMARD had a claim for a baseline serum creatinine test (68.0%-70.3%) and baseline liver function test (69.3%-71.0%). CONCLUSIONS: Findings suggest that a majority of RA patients are attaining patient quality process measures, although a considerable proportion of patients (approximately 25%) may be receiving suboptimal care. Further studies are warranted to understand whether attainment of these measures translates into better outcomes.
25993395 Functional Profiling of 2-Aminopyrimidine Histamine H4 Receptor Modulators. 2015 Sep 24 Histamine is an important endogenous signaling molecule that is involved in a number of physiological processes including allergic reactions, gastric acid secretion, neurotransmitter release, and inflammation. The biological effects of histamine are mediated by four histamine receptors with distinct functions and distribution profiles (H1-H4). The most recently discovered histamine receptor (H4) has emerged as a promising drug target for treating inflammatory diseases. A detailed understanding of the role of the H4 receptor in human disease remains elusive, in part because low sequence similarity between the human and rodent H4 receptors complicates the translation of preclinical pharmacology to humans. This review provides an overview of H4 drug discovery programs that have studied cross-species structure-activity relationships, with a focus on the functional profiling of the 2-aminopyrimidine chemotype that has advanced to the clinic for allergy, atopic dermatitis, asthma, and rheumatoid arthritis.
27605127 Infection and revision rates following primary total knee arthroplasty in patients with rh 2017 Dec PURPOSE: This meta-analysis compared infection and revision rates in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) who underwent total knee arthroplasty (TKA). Rates of superficial wound and deep periprosthetic infections were compared in the groups, as were whether revision rates associated with infectious and noninfectious causes differed in the RA and OA groups. METHODS: Studies were included in the meta-analysis if they (1) compared infection and revision rates after primary TKA in RA and OA patients; (2) directly compared superficial wound and deep periprosthetic infection rates in RA and OA patients who underwent primary TKA; and (3) reported the actual numbers of RA and OA patients who underwent TKA and developed postoperative infection and/or required revision. RESULTS: The rate of superficial wound infections after primary TKA was similar in the RA and OA groups (15/258 [5.8 %] vs. 77/1609 [4.7 %]; odds ratio [OR] 1.12, 95 % confidence interval [CI] 0.36-3.46; P = n.n.), but the deep infection rate was significantly higher in RA than in OA patients (229/7651 [3.0 %] vs. 642/68628 [0.9 %]; OR 2.04, 95 % CI 1.37-3.05; P < 0.001). The proportion of subjects who required revision resulting from infection after TKA was significantly higher in the RA than in the OA group (86/8201 [1.0 %] vs. 555/118755 [0.5 %]; OR 1.89, 95 % CI 1,34-2.66; P < 0.001), whereas the proportion of subjects requiring revision due to noninfectious causes did not differ significantly (46/594 [7.7 %] vs. 52/904 [5.7 %]; OR 1.22, 95 % CI 0.74-2.00; P = n.n.) CONCLUSION: Following primary TKA, RA patients had a significantly higher rate of deep periprosthetic infections than OA patients, but their superficial infection rates were similar. The revision rate due to infectious causes was significantly higher in RA than in OA patients, but their revision rates due to noninfectious causes did not differ. Therefore, the surgeon should fully explain to RA patients scheduled to undergo primary TKA that, compared to OA patients, they are more likely to experience a deep infection postsurgery. LEVEL OF EVIDENCE: Meta-analysis Level III.
26743575 Cerebral vasculitis as a major manifestation of rheumatoid arthritis. 2015 Oct OBJECTIVE AND IMPORTANCE: Cerebral vasculitis (CV) is a rare described complication of rheumatoid arthritis (RA). Although the most frequent neurological manifestations of RA are peripheral neuropathy and cervical spinal cord compression due to subluxation of the cervical vertebrae, CV can be seen especially in patients with seropositive and long-standing RA. CLINICAL PRESENTATION: We report two cases of CV associated with RA. Both patients had no extraarticular manifestations and RA clinics were under control. Our first case is a 30-years-old woman with seropositive RA for 15 years who had suddenly onset left facial and upper extremity weakness. In magnetic resonance imaging (MRI) DWI, hyperintensity in frontotemporal region due to acute ischaemia was detected. The new lacuner acute ischaemic lesions in right precentral gyrus, bilateral frontoparietal and corpus callosal region were detected in the control MRI. The cerebral MR angiography and transcranial doppler findings were consistent with CV. The patient responded favourably to pulse methylprednisolone and oral azathiopurine treatments. The second patient is a 52-year-old man who had been RA for 29 years. He admitted to our neurology clinic with speech difficulty and right upper extremity minimal weakness. Magnetic resonance imaging DWI showed left parietooccipital acute ischaemia which was progressed within a week and a new right parietooccipital ischaemia was added. His cerebral MR angiography and cerebral angiography were concordant with CV. The cyclophosphamide therapy was started since the cerebral ischaemia was progressed during pulse methylprednisolone and he responded well to this therapy. CONCLUSION: CV due to RA is an uncommon serious complication which can be life-threatening. Therefore clinicians should be aware of the possibility of CV especially in progressive strokes in RA.
26474773 Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta 2016 Apr The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR] = 1.155, 95 % confidence interval [CI] = 1.069-1.249, p = 2.7 × 10(-5)). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR = 1.273, 95 % CI = 1.193-1.359, p < 1.0 × 10(-9)), but not in Caucasians (OR = 1.024, 95 % CI = 0.973-1.078, p = 0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR = 2.311, 95 % CI = 1.1.858-2.875, p < 1.0 × 10(-9)) and Caucasians (OR = 1.523, 95 % CI = 1.157-2.004, p = 0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR = 1.547, 95 % CI = 1.247-1.919, p = 7.1 × 10(-6)) and Caucasians (OR = 1.096, 95 % CI = 1.025-1.172, p = 0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR = 1.263, 95 % CI = 1.153-1.384, p = 5.8 × 10(-8)), but not in Caucasians (OR = 1.123, 95 % CI = 0.980-1.287, p = 0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.