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ID PMID Title PublicationDate abstract
26568556 Development of key performance indicators to evaluate centralized intake for patients with 2015 Nov 14 INTRODUCTION: Centralized intake is integral to healthcare systems to support timely access to appropriate health services. The aim of this study was to develop key performance indicators (KPIs) to evaluate centralized intake systems for patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Phase 1 involved stakeholder meetings including healthcare providers, managers, researchers and patients to obtain input on candidate KPIs, aligned along six quality dimensions: appropriateness, accessibility, acceptability, efficiency, effectiveness, and safety. Phase 2 involved literature reviews to ensure KPIs were based on best practices and harmonized with existing measures. Phase 3 involved a three-round, online modified Delphi panel to finalize the KPIs. The panel consisted of two rounds of rating and a round of online and in-person discussions. KPIs rated as valid and important (≥7 on a 9-point Likert scale) were included in the final set. RESULTS: Twenty-five KPIs identified and substantiated during Phases 1 and 2 were submitted to 27 panellists including healthcare providers, managers, researchers, and patients in Phase 3. After the in-person meeting, three KPIs were removed and six were suggested. The final set includes 9 OA KPIs, 10 RA KPIs and 9 relating to centralized intake processes for both conditions. All 28 KPIs were rated as valid and important. CONCLUSIONS: Arthritis stakeholders have proposed 28 KPIs that should be used in quality improvement efforts when evaluating centralized intake for OA and RA. The KPIs measure five of the six dimensions of quality and are relevant to patients, practitioners and health systems.
27214848 Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease 2016 Nov OBJECTIVE: Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte-driven inflammation through a transforming growth factor β1-dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. METHODS: Collagen-induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss-of-function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C-reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. RESULTS: Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin-6 in the blood. Similarly, rs12212067 (a single-nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. CONCLUSION: Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage.
25553833 Overview of biologic treatments in the elderly. 2015 May As life expectancies rise, the number of elderly people with inflammatory rheumatic diseases will continue to grow. Treatment of this frail population, whose clinical features differ from those of younger subjects, poses new challenges to healthcare systems. However, this issue is rarely addressed in the current literature. Thanks to their targeted mechanism of action, biologics represent one of the major therapeutic advances of the last 15 years, but their use in the elderly has been slow in developing. Published data, derived mainly from cohorts, focus on the use of TNF inhibitors in rheumatoid arthritis and show that these treatments are effective and generally well tolerated. Nevertheless, the risk of infection and cancer, particularly skin and lymphoid malignancies, must not be neglected. The use of these biologics as second-line treatment improves patient outcomes and comfort, while reducing consumption of the widely used and more deleterious drugs such as glucocorticoids and non-steroidal anti-inflammatory drugs. Additional studies on biologics, focusing on the longer term and in indications apart from anti-TNF therapies in rheumatoid arthritis should help overcome some of the reluctance and promote the rational use of these drugs in the elderly.
26866831 Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First-Degre 2016 Aug OBJECTIVE: To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first-degree relatives (FDRs) of RA patients. METHODS: We evaluated RA risk factors and inflammatory joint signs in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included 5 HLA-DRB1 shared epitope alleles and 45 RA-associated single-nucleotide polymorphisms; loci were combined using genetic risk scores weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA-related autoantibodies were assessed at baseline. Physical examination was performed at baseline and 2-year follow-up, by observers who were blinded with regard to autoantibody status, to assess inflammatory joint signs as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with inflammatory joint signs. RESULTS: We analyzed 966 non-Hispanic white FDRs at baseline and 262 at 2-year follow-up after excluding those with inflammatory joint signs at baseline. The mean ± SD age was 47.2 ± 15.5 years, 71% were female, and 55% were shared epitope positive. Smoking >10 pack-years was associated with inflammatory joint signs at baseline (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26-2.82]) and at 2 years (OR 2.66 [95% CI 1.01-7.03]), compared to never smokers. There was a significant interaction between smoking and age with regard to risk of inflammatory joint signs (P = 0.02). FDRs younger than 50 years with >10 pack-years had the highest risk of inflammatory joint signs (OR 4.39 [95% CI 2.22-8.66], compared to never smokers younger than 50 years). CONCLUSION: In a high-risk cohort of FDRs, smoking and age were associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Further prospective investigations of the factors affecting the transitions between preclinical RA phases are warranted.
28383601 Temporomandibular joint involvement in rheumatoid arthritis patients: association between 2016 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and synovial hyperplasia, which usually affects multiple joints. The temporomandibular joint (TMJ) becomes susceptible to the development of changes resulting from RA. The aim of this study was to evaluate the presence of TMD and degenerative bone changes in TMJ in patients diagnosed with RA (rheumatoid arthritis). The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) questionnaire was used for clinical evaluation of the TMJ and for TMD classification of 49 patients of both sexes and all ages. Individuals who had already undergone prior treatment for TMD and/or with a history of craniofacial trauma were excluded. The participants underwent cone beam computed tomography (CBCT) exams to assess possible degenerative changes in the mandibular condyle and the articular eminence. The frequencies of the changes found are presented and the possible associations between clinical and CT findings analyzed using the chisquare test. It was found that 75% of the patients had complaints of pain in the orofacial region, including arthralgia, myalgia or both. As for the diagnoses, 100% of the sample was diagnosed as RDC/TMD Group III (arthralgia, osteoarthritis or osteoarthrosis). The presence of degenerative bone changes was found in 90% of the subjects, the most prevalent being flattening (78.7%) and osteophytes (39.3%). The association test suggested a greater tendency to develop degenerative changes in asymptomatic individuals (p = 0.01). The asymptomatic nature of the involvement of the TMJ in RA can hide structural damage seen in imaging. Thus, the importance of early diagnosis and treatment to reduce structural and functional damage is emphasized.
26753206 [Insulin resistance and metabolic syndrome - a different image of disorders in rheumatoid 2015 INTRODUCTION: Chronic inflammation is associated with impaired glucose tolerance and insulin resistance (IR) phenomenon. Proinflammatory cytokines such as interleukin-6 and tumor necrosis factorTNF-α play a significant role in the pathogenesis of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, the relationships between prevalence of IR and metabolic syndrome (MetS) in patients (pts) with a different rheumatic diseases have not been yet well characterized. MATERIAL AND METHODS: The study was conducted in 102 pts aged 18-65 years, including 60 pts with RA (45 women, 15 men) and 42 pts with AS (4 women, 38 men). In all of pts serum fasting hemoglobin (Hb), fibrinogen, uric acid, vitamin D3, lipids, ESR, CRP, IL-6, hs-CRP, SAA, IL-6 sR, RF-IgM titer, a-CCP, and glucose, insulin after 0, 30, 60, 120 min during the oral glucose tolerance test with the calculation of indicators of IR (HOMA-IR, insulin/glucose) and insulin sensitivity (QUICKI, Matsuda) were performed. Moreover, BMI, WHR, disease activity indices (DAS28 in RA, BASDAI in AS) and the criteria for diagnosis of MetS were evaluated. The results were statistically analyzed. RESULTS: IR and MetS occur more frequently in patients with RA. Forthese disorders a strongly correlation with BMI and WHR, whereas not with disease activity indices has been shown. RA patients with MetS had a higher titers of RF-IgM and hemoglobin concentration. CONCLUSIONS: Patients with RA have an increased risk of MetS with IR compared to patients with AS. In addition, higher RF-IgM titer increases the risk of developing MetS in RA.
25370956 CD8+ T cell profiles in patients with rheumatoid arthritis and their relationship to disea 2015 Feb OBJECTIVE: CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their role in disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8+ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA. METHODS: CD8+ T cell phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex- and age-matched healthy controls. Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines, and proteolytic enzymes in CD8+ T cells was evaluated using flow cytometry. RESULTS: PB CD8+ T cells from RA patients with active disease exhibited an effector (CD27-CD62L-) phenotype (P = 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor α [TNFα], interferon-γ [IFNγ], interleukin-6 [IL-6], IL-17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 (P < 0.001), but lower cytokine production was observed. SF CD8+ T cells from RA patients expressed more robust effector memory (CD27+CD62L-) and activated (CD69+) profiles compared to the T cell subsets in paired PB samples. Production of cytokines (IL-6, IL-17A, and IFNγ) by CD8+ T cells from RA PB was positively correlated within individual donors. Moreover, production of cytokines (TNFα, IFNγ, and IL-17A) by CD8+ T cells from RA PB positively correlated with the Disease Activity Score in 28 joints. CONCLUSION: The activation status and proinflammatory potential of CD8+ T cell subsets observed in the RA patients in this study strongly suggest that a phenotype of local and systemic cytotoxic effector T cells plays a role in this disease.
25647268 Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vit 2015 Apr Macrophage migration inhibitory factor (MIF) enhances activation of leukocytes, endothelial cells and fibroblast-like synoviocytes (FLS), thereby contributing to the pathogenesis of rheumatoid arthritis (RA). A MIF promoter polymorphism in RA patients resulted in higher serum MIF concentration and worsens bone erosion; controversially current literature reported an inhibitory role of MIF in osteoclast formation. The controversial suggested that the precise role of MIF and its putative receptor CD74 in osteoclastogenesis and RA bone erosion, mediated by locally formed osteoclasts in response to receptor activator of NF-κB ligand (RANKL), is unclear. We reported that in an in vivo K/BxN serum transfer arthritis, reduced clinical and histological arthritis in MIF(-/-) and CD74(-/-) mice were accompanied by a virtual absence of osteoclasts at the synovium-bone interface and reduced osteoclast-related gene expression. Furthermore, in vitro osteoclast formation and osteoclast-related gene expression were significantly reduced in MIF(-/-) cells via decreasing RANKL-induced phosphorylation of NF-κB-p65 and ERK1/2. This was supported by a similar reduction of osteoclastogenesis observed in CD74(-/-) cells. Furthermore, a MIF blockade reduced RANKL-induced osteoclastogenesis via deregulating RANKL-mediated NF-κB and NFATc1 transcription factor activation. These data indicate that MIF and CD74 facilitate RANKL-induced osteoclastogenesis, and suggest that MIF contributes directly to bone erosion, as well as inflammation, in RA.
27599663 Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Tocilizumab in Patients With 2017 Apr Tocilizumab is a humanized anti-interleukin-6 receptor antibody for treating rheumatoid arthritis. Pharmacokinetic/pharmacodynamic analysis was performed on the 24-week double-blind parts of 2 randomized, controlled trials: SUMMACTA and BREVACTA. SUMMACTA compared subcutaneous tocilizumab 162 mg every week to intravenous tocilizumab 8 mg/kg every 4 weeks, whereas BREVACTA evaluated 162 mg subcutaneous tocilizumab every 2 weeks versus placebo. In addition to noncompartmental analysis, a 2-compartment population pharmacokinetic model, with first-order absorption (for subcutaneous) and linear and Michaelis-Menten elimination was used. Mean observed steady-state predose tocilizumab concentrations in week 24 were 40 and 7.4 μg/mL for subcutaneous every-week and every-2-week dosing, respectively, and 18 μg/mL for intravenous dosing. In the population PK model, body weight was an important covariate affecting clearance and volume of distribution. Mean ± SD population-predicted predose concentration for patients ≥100 kg was 23.0 ± 13.5 μg/mL for subcutaneous tocilizumab every week and 1.0 ± 1.6 μg/mL for every 2 weeks. Efficacy was lowest with subcutaneous every-2-week dosing in patients > 100 kg, reflecting lower exposure. The subcutaneous every-2-week regimen is not recommended for these patients. Pharmacodynamic responses were comparable for the every-week subcutaneous and every-4-week intravenous regimens and less pronounced with the every-2-week subcutaneous regimen. No trend was observed for increased adverse events with increasing tocilizumab exposure. The results of this analysis are consistent with the noninferiority of efficacy of the every-week subcutaneous regimen to the every-4-week intravenous regimen and the superiority of the every-2-week subcutaneous regimen to placebo. These results support the label recommendations for subcutaneous dosing of tocilizumab in rheumatoid arthritis patients.
26916550 Kinsenoside inhibits the inflammatory mediator release in a type-II collagen induced arthr 2016 Feb 25 BACKGROUND: Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the "King of medicine" in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. Kinsenoside is an essential and active compound of A. formosanus (Orchidaceae). However, the anti-arthritic activity of kinsenoside has still not been demonstrated. In the present study, we confirmed that the kinsenoside treatment rheumatoid arthritis induced by collagen-induced arthritis in mice. METHODS: Male DBA/1 J mice were immunized by intradermal injection of 100 μg of type II collagen in CFA. Kinsenoside was administered orally at a dose of 100 and 300 mg/kg once a day after 2nd booster injection. Paw swelling, arthritic score and histological change were measured. ELISA was used to measure cytokines including tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17) and interferon-γ (IFN-γ) in the splenocyte according to the manufacturer's instructions. RESULTS: Compared with model group, kinsenoside significantly inhibited paw edema and decreased the arthritis score and disease incidence. Histopathological examination demonstrated that kinsenoside effectively protected bone and cartilage of knee joint from erosion, lesion and deformation versus those from the CIA group. Kinsenoside also decreased IL-1β, TNF-α, and MMP-9 expression, and increased the expression of IL-10 in inflamed joints. The administration of kinsenoside significantly suppressed levels of TNF-α, IFN-γ, and IL-17, but increased concentrations of IL-10 in the supernatants of each of the splenocytes in CIA mice compared with that in the H2O-treated mice with CIA. Using flow cytometric analysis, we demonstrated that kinsenoside increases the population of CD4(+)CD25(+) regulatory T cells, thereby inhibiting the Th1 cell and B cell populations. Anticollagen IgG1 and IgG2a levels decreased in the serum of kinsenoside-treated mice. CONCLUSIONS: These results suggest that the administration of kinsenoside effectively suppressed inflammatory mediators' production and bone erosion in mice with collagen-induced arthritis showing the potential as an anti-arthritis agent.
27883186 Lactate at the crossroads of metabolism, inflammation, and autoimmunity. 2017 Jan For a long time after its discovery at the beginning of the 20th century, lactate was considered a waste product of cellular metabolism. Starting in the early '90s, however, lactate has begun to be recognized as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis (RA) synovitis, are characterized by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility. Importantly, this "stop migration signal" is dependent upon lactate's interference with intracellular metabolic pathways, specifically glycolysis. Furthermore, lactate promotes the switch of CD4(+) T cells to an IL-17(+) subset, and reduces the cytolytic capacity of CD8(+) T cells. These phenomena might be responsible for the formation of ectopic lymphoid structures and autoantibody production in inflammatory sites such as in RA synovitis, Sjogren syndrome salivary glands, and multiple sclerosis plaques. Here, we review the roles of lactate in the modulation of the inflammatory immune response.
25889222 Patients lacking classical poor prognostic markers might also benefit from a step-down glu 2015 Apr 9 INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. RESULTS: We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. CONCLUSION: In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. TRIAL REGISTRATION: EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.
27888965 Effects of Nursing Interventions on Depression of Patients With Rheumatoid Arthritis: A Me 2016 Dec INTRODUCTION: Previous randomized controlled trials have led to conflicting findings regarding the effects of nursing interventions on depression of patients with rheumatoid arthritis (RA). The purpose of this study was to use the meta-analytic approach to resolve these discrepancies. METHODS: We performed a systematic search of publications using MEDLINE, EMBASE, the Cochrane Library, and manual searches without language restrictions. Studies that met the following criteria were included: (1) randomized controlled trials; (2) duration of intervention≥4 weeks; (3) comparative control group; (4) adults with RA; (5) published studies in any language since reception; and (6) psychological symptoms assessed. We extracted relative risks (RRs) and 95% confidence internals (CIs) and pooled them using a random effect model. We carried out sensitivity analysis and assessed heterogeneity and publication bias. RESULTS: A total of 14 studies, including 1803 patients, were eligible for inclusion in the review. Depression symptom was assessed by questionnaires. In the pooled analysis, nursing interventions, including exercise training, medication guide, health education and psychotherapy were associated with the remission of depression (RR: -0.67; 95% CI: -0.89 to -0.46; P<0.01) with significant heterogeneity between studies (P<0.01). CONCLUSION: Nursing interventions may be important adjunctive therapies in the medical management of RA patients.
26159210 Clinical evaluation of periodontal disease in patients with rheumatoid arthritis: A cross- 2015 Oct OBJECTIVE: The aim of this study was to determine the presence of periodontal disease among patients with rheumatoid arthritis (RA) in comparison with a control group. METHOD AND MATERIALS: The study included 44 patients diagnosed with RA according to American Rheumatism Association (ARA) criteria, who were attending the Morales Meseguer Hospital Rheumatology Service (Murcia, Spain), and 41 control subjects. Patients younger than 18 years or patients suffering systemic diseases that could affect the immune system were excluded. Age, sex, smoking habits, alcohol consumption, and body mass index were registered. Each patient underwent a full periodontal examination. RESULTS: Bleeding on probing was significantly greater in the RA group (0.9 ± 0.36) than the control (P < .001). The Plaque Index was significantly higher in the RA group (0.76 ± 0.34) versus the control group (0.55 ± 0.2) (P < .001). RA patients showed a 0.13 increased risk of periodontal disease (95% confidence interval, 0.05-0.37). CONCLUSION: Patients with RA suffered a higher risk of periodontal disease and for this reason these patients must be instructed to intensify their oral hygiene regimes.
25744771 Use of exploratory factor analysis to ascertain the correlation between the activities of 2015 BACKGROUND AND OBJECTIVE: We evaluated a possible correlation between the clinical activities of rheumatoid arthritis (RA) and human parvovirus B19 (B19) infection using exploratory factor analysis (EFA). MATERIALS AND METHODS: RA patients were organized into two groups: 100 patients in the main group and 97 in the RA(DAS28) group. Four subgroups were defined from the main group according to the presence or absence of certain infection-specific markers: group I comprised 43 patients who had IgG antibodies against B19; group II, 25 patients with active B19 infection (B19-specific IgM antibodies and/or plasma viremia); group III, 19 patients with latent/persistent B19 infection (virus-specific sequences in peripheral blood leukocytes' DNA with or without B19-specific IgG antibodies), and group IV, 13 patients without infection markers. The RA(DAS28) group was divided into four subgroups similarly to the main group: group I, 35; group II, 31; group III, 19; and group IV, 12 patients. Disease-specific clinical values in both groups were analyzed employing EFA, and the RA(DAS28) group was additionally assessed using Disease Activity Score (DAS)28. RESULTS: RA activity was higher in patients who had markers of B19 infection. The highest activity of RA in both study groups was in patients with latent/persistent infection. In the RA(DAS28) group, according to DAS28, the highest activity of RA was in patients with active B19 infection. CONCLUSIONS: Using EFA and DAS28, a correlation between the clinical activity of RA and B19 infection was confirmed. These data suggest that EFA is applicable for medico-biological studies.
26178278 Miscarriage and Stillbirth in Women with Rheumatoid Arthritis. 2015 Sep OBJECTIVE: To examine the risk of pregnancy loss in women with rheumatoid arthritis (RA). METHODS: Cumulative numbers of early miscarriages (before gestational Week 12), late miscarriages (weeks 12-22), and stillbirths reported to the Medical Birth Registry of Norway in the period 1999-2009. RESULTS: There were 1578 women with RA and 411,130 reference women included in the study. Relative risks of early and late miscarriage in women with RA versus references were 1.2 (95% CI 1.1-1.3) and 1.4 (95% CI 1.1-1.7), respectively. There was no difference in stillbirth. CONCLUSION: The risk of miscarriage was slightly higher among women with RA than in references.
26010179 REAL-PANLAR Project for the Implementation and Accreditation of Centers of Excellence in R 2015 Jun OBJECTIVE: A consensus meeting of representatives of 16 Latin American and Caribbean countries and the REAL-PANLAR group met in the city of Bogota to provide recommendations for improving quality of care of patients with rheumatoid arthritis (RA) in Latin America, defining a minimum standards of care and the concept of center of excellence in RA. METHODS: Twenty-two rheumatologists from 16 Latin American countries with a special interest in quality of care in RA participated in the consensus meeting. Two RA Colombian patients and 2 health care excellence advisors were also invited to the meeting. A RAND-modified Delphi procedure of 5 steps was applied to define categories of centers of excellence. During a 1-day meeting, working groups were created in order to discuss and validate the minimum quality-of-care standards for the 3 proposed types of centers of excellence in RA. Positive votes from at least 60% of the attending leaders were required for the approval of each standard. RESULTS: Twenty-two opinion leaders from the PANLAR countries and the REAL-PANLAR group participated in the discussion and definition of the standards. One hundred percent of the participants agreed with setting up centers of excellence in RA throughout Latin America. Three types of centers of excellence and its criteria were defined, according to indicators of structure, processes, and outcomes: standard, optimal, and model. The standard level should have basic structure and process indicators, the intermediate or optimal level should accomplish more structure and process indicators, and model level should also fulfill outcome indicators and patient experience. CONCLUSIONS: This is the first Latin American effort to standardize and harmonize the treatment provided to RA patients and to establish centers of excellence that would offer to RA patients acceptable clinical results and high levels of safety.
26428206 Concomitant Methotrexate Protects Against Total Knee Arthroplasty in Patients with Rheumat 2015 Dec OBJECTIVE: To determine the effects of concomitant methotrexate (MTX) on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with rheumatoid arthritis (RA) during longterm treatment with tumor necrosis factor (TNF) inhibitors. METHODS: A total of 155 patients with RA (310 knee joints) received TNF inhibitors at our institute between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or swollen) knee joints in 68 patients were retrospectively studied over the course of a minimum of 5 years of followup. The median (interquartile range) followup period was 8.1 (7.0-9.3) years. All data were analyzed using the knee joint as the statistical unit of analysis. TKA during treatment with TNF inhibitors was used as the outcome variable in predictive analyses. The cumulative incidence of TKA was compared by concomitant or no MTX use (MTX±). RESULTS: There were 79 subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates, the cumulative incidence of TKA for the MTX+ group was significantly lower than that for the MTX- group (24% vs 45% at 5 yrs, respectively, p = 0.035). Multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX (HR 0.44, 95% CI 0.22-0.89), Larsen grade (HR 2.93, 95% CI 1.94-4.41), and older age at baseline (HR 1.04, 95% CI 1.01-1.08) were independent predictors of TKA. CONCLUSION: Concomitant MTX reduces the incidence of TKA by 56% in patients with RA during longterm treatment with TNF inhibitors.
27142966 Efficacy of intensive immunosuppression in exacerbated rheumatoid arthritis-associated int 2017 Jan OBJECTIVES: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role of intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate the clinical characteristics and efficacy of immunosuppressive treatment in exacerbated RA-ILD. METHODS: Clinical data, including respiratory function, imaging, treatment, and prognosis, were retrospectively collected for 17 patients with RA-ILD who required hospitalization at the University of Tokyo Hospital due to an acute exacerbation (12 patients) or subacute exacerbation (5 patients). RESULTS: Patients with RA-ILD demonstrated a significantly higher titers of anticyclic citrullinated peptide antibodies compared with RA patients in Japanese Ninja registry, suggesting the role of adaptive immunity. Immunosuppressive treatment suppressed the deterioration of pulmonary functions with improved ground grass opacity and consolidation. In particular, in patients with less fibrosis on computed tomography (CT) images showed a better response to treatment. Although five patients treated with combination therapy, including cyclophosphamide, showed a severely decreased lung volume, these intensive therapies provided a good prognosis without fatalities for the average observation period of 474 days. CONCLUSIONS: Immunosuppressive therapy is effective for exacerbations of RA-ILD. For severe cases with low respiratory function, intensive therapy, including cyclophosphamide, has a potential to improve the prognosis.
27255888 Antibodies directed against endogenous and exogenous citrullinated antigens pre-date the o 2016 Jun 3 BACKGROUND: Anti-citrullinated-peptide antibodies (ACPA) have been detected in individuals with developing rheumatoid arthritis (RA) before the onset of symptom, with an initially limited spectrum of reactivities that gradually broadens. The aim was to analyze the evolution of ACPA response pre-dating symptom onset, using four selected citrullinated exogenous and endogenous antigens. METHODS: A cohort of 521 individuals sampled before symptoms of RA appeared and 272 population controls were identified from the Biobank of Northern Sweden; 241 samples from patients with early RA were also collected. ACPA were detected by ELISA on viral citrullinated peptides (VCP) derived from Epstein-Barr-virus nuclear antigen (EBNA)1 and EBNA2 (VCP1 and VCP2) and histone-4-derived citrullinated peptides (HCP1 and HCP2). RESULTS: In pre-symptomatic individuals vs. patients with early RA, anti-VCP1 antibodies were detected in 10.4 % vs. 36.1 %, anti-VCP2 in 17.1 % vs. 52.3 %, anti-HCP1 in 10.2 % vs. 37.3 %, and anti-HCP2 in 16.3 % vs. 48.5 %, respectively. Anti-VCP and anti-HCP concentrations were significantly increased in pre-symptomatic individuals vs. controls (p < 0.001) and were increased approaching symptom onset. Anti-VCP and anti-HCP appeared simultaneously (median (IQR) 5.3 (6) years before symptom onset) and in combination yielded a high-risk ratio for disease development (OR = 8.0-18.9). Anti-VCP2 and anti-HCP2 antibodies were associated with HLA-DRB1*0401 in pre-symptomatic individuals. Three peptidylarginine deiminase (PAD)I3/PADI4 single nucleotide polymorphisms (SNPs) were significantly associated with anti-HCP1. CONCLUSIONS: Anti-VCP and anti-HCP antibodies pre-date symptom onset and predict disease development, but no hierarchy of citrullinated epitopes can be identified. These results suggest that no inciting citrullinated antigen so far described is common to all patients with RA. The association between PADI3/PADI4 polymorphism and anti-HCP1 antibodies suggests a novel link between deimination and production of ACPA.