Browse

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

ID PMID Title PublicationDate abstract
27149461 Cancer Risk in Patients With Inflammatory Systemic Autoimmune Rheumatic Diseases: A Nation 2016 May The aim of this study was to determine whether inflammation is related to cancer development, and whether the incidence of cancer is increased and occurs in a site-specific manner in patients with systemic autoimmune rheumatic diseases (SARDs).This study included a nationwide dynamic cohort of patients with various newly diagnosed SARDs from 1997 to 2010 with follow-up until 2012.This study included 75,123 patients with SARDs. During 562,870 person-years of follow-up, 2844 patients developed cancer. Between 1997 and 2010, the highest number of newly diagnosed SARDs cases were rheumatoid arthritis (n = 35,182), followed by systemic lupus erythematosus (SLE, n = 15,623), Sjögren syndrome (n = 11,998), Kawasaki disease (n = 3469), inflammatory bowel disease (n = 2853), scleroderma (n = 1814), Behçet disease (n = 1620), dermatomyositis (n = 1119), polymyositis (n = 811), and vasculitis other than Kawasaki disease (n = 644). A significant standardized incidence ratio (SIR) of overall cancer was observed for patients with SLE (1.41; 95% confidence interval [CI], 1.28-1.56), Sjögren syndrome (1.19; 95% CI, 1.08-1.30), scleroderma (1.27; 95% CI, 1.02-1.59), dermatomyositis (4.79; 95% CI, 4.01-5.73), polymyositis (1.47; 95% CI, 1.05-2.06), vasculitis excluding Kawasaki disease (1.75; 95% CI, 1.20-2.55), and Kawasaki disease (2.88; 95% CI, 1.60-5.20). Overall, patients with most SARDs had a significantly higher risk of inflammation-associated site-specific cancers and hematologic malignancies.This study confirms that autoimmunity is associated with site-specific and hematological malignancies and provides clinical evidence of an association between inflammation and subsequent site-specific cancer development. These findings support the importance of inflammation in site-specific organ system carcinogenesis.
27009826 Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cach 2016 Jul OBJECTIVE: Altered energy expenditure may contribute to the nutritional complications of RA, metabolic syndrome (MS) and rheumatoid cachexia (RC). The main aim of this study was to evaluate whether the altered resting energy expenditure (REE) and physical activity (PA)-related energy expenditure (EE) are related to the duration of RA and inflammatory activity and nutritional complications in RA. METHODS: Among patients with well-characterized RA (duration, activity: DAS28 ESR), we measured REE by indirect calorimetry, and PA-EE by actimetry (SenseWear Armband). MS was defined according to the International Diabetes Federation criteria and RC from DXA body composition analysis. The relations between the characteristics and nutritional complications, and EE were analysed by linear regression. RESULTS: Fifty-seven patients were included [73% women, age 57 (10) years] with a wide range of disease duration: 3.8 (3.0) years, and DAS28 ESR: 3.9 (1.4). The mean REE was 1486 (256) kcal/day, associated with the DAS28 ESR (β = +0.21, P = 0.02 after adjusting for gender and fat free mass). The prevalence of MS and RC was, respectively, 24 and 18%, and they were unrelated to each other. The patients with MS and/or RC had double the longstanding RA score (P < 0.05), twice the homeostasis model assessment of insulin resistance values (P = 0.052) and halved levels of PA (P < 0.05 for metabolic equivalent tasks (METs) and number of steps/day). Two modifiable factors were associated with the presence of MS and/or RC: a low level of PA as METs [exp(B) = 0.03, P = 0.009] and the use of glucocorticoids [exp(B) = 4.08, P = 0.046]. CONCLUSION: Low levels of PA and treatment by glucocorticoids are associated with the nutritional complications of RA, suggesting the potential for therapeutic interventions.
26575013 Ankylosis of the wrist bones in patients with rheumatoid arthritis: a study with extremity 2016 Jan OBJECTIVES: Ankylosis, or spontaneous bone fusion, of the small joints of the hand is a rare event in patients with rheumatoid arthritis (RA), being observed in 0.8% of them on conventional radiographs. It is associated with long-lasting and severe disease. In other settings, such as fracture healing, bone fusion is a reparative process. The aim of this paper is the study of the frequency of wrist ankylosis in patients with RA in comparison with other arthritides; to correlate ankylosis with disease activity. METHODS: A total of 94 patients affected by RA, 71 patients with different rheumatic conditions and 42 controls with no joint disease or with slight hand osteoarthritis were studied. DAS-28 CRP was calculated in patients with RA and psoriatic arthritis. MRI of the clinically most involved wrist was performed with a 0.2 T, extremity-dedicated MRI system. RESULTS: Of RA patients, 10/94 (10.6%) showed ankylosis in comparison with 2/113 (1.8%) controls (p=0.015). RA patients with ankylosis had longer disease duration (p=0.019) but similar disease activity. CONCLUSIONS: MRI-defined bone ankylosis is frequent in RA. It is not limited to seronegative spondyloarthritides and may be part of the bone damage observed in RA.
27557840 Claims for disease-modifying therapy by Alberta non-insured health benefits clients. 2016 Aug 24 BACKGROUND: Uncontrolled disease activity in inflammatory diseases of the joints, skin and bowel leads to morbidity and disability. Disease-modifying therapies are widely used to suppress this disease activity, but cost-coverage is variable. For Treaty First Nations and Inuit people in Canada without alternative private or public health insurance, cost-coverage for disease-modifying therapy is provided through Non-Insured Health Benefits (NIHB). Our objective was to describe the prevalence and patterns of treatment with disease-modifying therapy for the NIHB claimant population, and also examine adjuvant therapy (analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids) use. METHODS: Cases (n = 2512) were defined by ≥1 claim for a disease-modifying anti-rheumatic drug (DMARD) or biologic between 1999 and 2012 in the NIHB pharmacy claim database. The proportion of the population with claims for individual agents and drug classes annually was calculated to estimate annual incidence and prevalence rates for use of disease-modifying therapy, and the prevalence of use of individual DMARDs, biologics and adjuvants. Differences in the proportion accessing adjuvant therapies and median doses in the 6 months following initiation of disease-modifying therapies was estimated. RESULTS: The incidence rate of treatment was calculated at an average of 127.5 cases per 100,000 population between 2001 and 2012, and the cumulative prevalence, accounting for patients lost to the database, increased and then stabilized at 1.3 % in the last three years of the study. Annual dispensation of methotrexate, combination DMARD therapy and biologic therapy approached 35 %, 19 %, and 10 % of the cohort respectively. A declining prevalence of claims for acetaminophen (28 % to 15 %) and anti-inflammatories (73 % to 63 %) occurred from 2000 to 2012, however corticosteroid (32 %) and opioid (65 %) dispensation remained stable. The proportion of patients with claims for NSAIDs (69.9 % to 61.1 %, p = 0.002), oral corticosteroids (45.4 % to 33.6 %, p < 0.001) and parenteral corticosteroids (16.2 % to 8.3 %, p = 0.002) decreased in the 6 months following biologic initiation. CONCLUSIONS: The proportion of NIHB clients with active claims for disease-modifying therapy is lower than expected based on existing epidemiologic knowledge of the prevalence of inflammatory conditions in the First Nations and Inuit populations. These findings should be further explored in order to optimize treatment outcomes for NIHB claimants with inflammatory disease.
26808318 Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on Major Eicosanoids: A Systemati 2016 BACKGROUND: Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials. METHOD AND FINDINGS: A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine-derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, -0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non-autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis. CONCLUSIONS: Marine-derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA.
27294995 Factors Associated With Activity Limitations in People With Rheumatoid Arthritis. 2016 Jul OBJECTIVE: We evaluated factors contributing to activity limitations in people with rheumatoid arthritis (RA) according to the International Classification of Functioning, Disability and Health model. METHOD: In a cross-sectional study, we measured five activity constructs in 81 people with RA. RESULTS: Multiple regression analysis revealed the following results for the five constructs: (1) RA Activities (R² = .512) included handgrip strength, range of motion deficit, deformity, and mental health; (2) Upper-Limb Activities (R² = .473) included time since diagnosis, dexterity, handgrip strength, and range of motion deficit; (3) Timed Activities (R² = .320) included dexterity and work activities; (4) Physical Autonomy Activities (R² = .562) included range of motion deficit, vitality, pain, and functional classification; and (5) Physical Conditions for Activities (R² = .416) included functional classification and vitality. CONCLUSION: Factors most associated with activity limitations were handgrip strength and hand range of motion deficits. Activity limitations in people with RA are multifactorial.
25159156 IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint 2015 Mar OBJECTIVE: We earlier found that TNFα but not interleukin (IL)-17 is indispensable in the pathogenesis of spontaneously occurring rheumatoid arthritis (RA)-like disease in our newly established FcγRIIB-deficient C57BL/6 (B6) mouse model, designated KO1. Here, we examined the role of IL-6 in the pathogenesis of RA features in KO1, with particular reference to cartilage and bone destruction in arthritic joints. METHODS: To evaluate the preventive effect of MR16-1, a rat anti-mouse IL-6 receptor (IL-6R) mAb, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with MR16-1 for 6 months, the second treated with normal rat IgG, as a control, and the third left untreated. The incidence and severity of arthritis, immunological abnormalities, and transcription levels of receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines/chemokines in ankle joint tissues were compared among the three groups. The therapeutic effect of MR16-1 was examined by treating 7-month-old KO1 mice in the early stages of arthritis for 2 months. RESULTS: Compared with the findings in the KO1 mice left untreated or treated with normal rat IgG, the development of arthritis was markedly suppressed in mice with MR16-1 treatment started from preclinical stages. The suppression was associated with the decrease in production of autoantibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP). Histologically, marked synovitis, pannus formation, and cartilage and bone destruction associated with the increase in tartrate-resistant acid phosphatase (TRAP)-positive osteoclast generation were evident in the two control groups; however, these findings were virtually absent in MR16-1-treated mice. Real-time PCR analysis revealed that the up-regulated expression levels of MCP-1, IL-6, and TNFα, and the aberrantly high RANKL/OPG expression ratio in synovial joint tissues from the two control groups of mice with overt arthritis were significantly suppressed in MR16-1-treated mice. In mice with therapeutic MR16-1 treatment, there was no progression in arthritis score and the RANKL/OPG ratio in joint tissues was significantly suppressed. CONCLUSIONS: Administration of an anti-IL-6R mAb ameliorated spontaneously occurring RA-like disease features, indicating that IL-6, as well as TNFα, plays a pivotal role in the pathogenesis of RA in KO1 mice. Current studies showed that, in addition to the role in enhancing autoantibody production, IL-6 promotes synovial tissue inflammation and osteoclastogenesis, leading to the severe synovitis with pannus formation and the progressive cartilage and bone destruction in multiple joints.
26773113 A Prospective Study Investigating Prediagnostic Leukocyte Telomere Length and Risk of Deve 2016 Feb OBJECTIVE: To prospectively examine the association between leukocyte telomere length (LTL) and subsequent rheumatoid arthritis (RA) development in women. METHODS: Using a case-control design nested within the prospective Nurses' Health Study (NHS), NHS II (NHSII), and Women's Health Study (WHS), each validated case of RA with a prediagnostic blood sample was matched to 3 controls by cohort, age, menopausal status, postmenopausal hormone therapy, and blood collection covariates. We measured telomere length in genomic DNA extracted from stored buffy coat samples using quantitative PCR. We used unconditional logistic regression to determine OR and 95% CI, and random-effects metaanalysis to combine study results. RESULTS: In total, we analyzed 296 incident RA cases and 827 matched controls. Mean age of diagnosis among women who developed RA was 60.5 in NHS/NHSII and 61.3 in WHS. Metaanalysis demonstrated that longer prediagnostic LTL was associated with increased RA risk when women in the longest versus shortest LTL tertile were compared (OR 1.51, 95% CI 1.03-2.23, Pheterogeneity = 0.27). However, statistically significant between-study heterogeneity was observed for the intermediate tertile category (Pheterogeneity = 0.008). We did not observe heterogeneity by menopausal status, inflammatory cytokine levels, age at diagnosis, age at blood collection, body mass index, seropositivity, or HLA-DRβ1 shared epitope status. CONCLUSION: Our results do not support an involvement for short LTL preceding RA development.
27477805 Defining criteria for rheumatoid arthritis patient-derived disease activity score that cor 2016 Nov OBJECTIVE: Two versions of a patient-based DAS (PDAS) 1 and 2 (with and without ESR) have been developed and validated in RA. The objective of this study was to define PDAS1- and PDAS2-based criteria for remission, low, moderate and high disease activity and responses to treatment. METHOD: Using receiver operating characteristic curves, the optimal thresholds for PDAS1 and PDAS2 that correspond to validated assessor-based DAS (DAS28) and Clinical Disease Activity Index (CDAI) disease statuses were determined. Data from RA patients initiated on disease-modifying drugs were used to determine optimal thresholds for PDAS1 and PDAS2 that corresponded to EULAR good and moderate responses. Agreement with DAS28, CDAI and EULAR response criteria was assessed by Cohen's κ statistic. RESULTS: Threshold for PDAS1 and PDAS2 demonstrated fair to moderate agreement with DAS28 [κ = 0.44 (95% CI: 0.40, 0.50) and 0.31 (95% CI: 0.25, 0.38)] and CDAI [κ = 0.27 (95% CI: 0.22, 0.33) and 0.42 (95% CI: 0.35, 0.49)] disease statuses, respectively, which was similar to agreement between DAS28 and CDAI [κ = 0.54 (95% CI: 0.46, 0.61)] within this group. Agreement of EULAR good and moderate response with PDAS1 and PDAS2 was κ = 0.46 (95% CI: 0.27, 0.64) and 0.38 (95% CI: 0.20, 0.56), respectively. CONCLUSION: Thresholds for disease activity statuses and response to treatment for PDAS1 and PDAS2 have been established. They have comparable agreement to assessor-based criteria.
27409579 Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases. 2016 Aug BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.
26314565 Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD 2016 Jan OBJECTIVE: Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA. METHODS: Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127(low) Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiles. RESULTS: No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin-17 [IL-17], interferon-γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL-1β, IL-1 receptor antagonist, IL-7, CCL3, or CCL4) by autologous lipopolysaccharide-activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL-6, IL-8, IL-12, IL-15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls. CONCLUSION: Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.
26114946 The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Ri 2015 OBJECTIVES: To assess whether treatment with one of three novel biological DMARDs; rituximab, abatacept or tocilizumab reduce cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: This is an open, observational and prospective study with visits at baseline, 3, 6, and 12 months. Patients were assigned to receive rituximab, abatacept or tocilizumab according to clinical indications assessed by an independent rheumatologist. Disease activity was quantified by the disease activity score (DAS28) and extensive ultrasonography. CVD risk was assessed by total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), blood pressure and arterial stiffness measurements [pulse wave velocity (PWV) and augmentation index (AIx)]. Within group change in disease activity and CVD risk over 3 months was explored using paired samples bivariate tests. Predictors of change in CVD risk at 3 months were identified in linear regression models. Changes in CVD risk markers over the 12- month follow-up in patients receiving rituximab were assessed by mixed models repeated analyses. RESULTS: 24 patients on rituximab, 5 on abatacept and 7 on tocilizumab were included. At 3 months PWV was significantly reduced in the tocilizumab group only, but at 12 months rituximab patients showed a significant reduction in PWV. Reduced inflammation at 3 months was associated with increased TC and HDL-c in the entire cohort. CONCLUSION: Treatment with tocilizumab and rituximab reduces PWV, a marker of CVD risk, in patients with RA.
27048296 Work-related discussions between French rheumatologists and their rheumatoid arthritis pat 2016 Aug BACKGROUND: Rheumatoid arthritis (RA) causes significant impairment of physical function, and thus adversely affects patients' ability to work. AIMS: To document how often work limitations are discussed by rheumatologists and RA patients during consultations. METHODS: We conducted an observational study in a sample of French rheumatologists and in a parallel sample of patients recruited by pharmacists. We asked all rheumatologists in France practising in private practice or mixed practice (private practice and hospital) to participate in a telephone survey about their most recent consultation with an RA patient. Randomly selected pharmacists recruited RA patients to complete a questionnaire about their most recent consultation with their rheumatologist. We included patients aged 20-59, with a paid job or unemployed. We calculated the proportion of consultations including work-related discussions in both samples. RESULTS: Of the 1737 rheumatologists contacted, 153 (9%) described consultations with eligible patients. Of the 1200 pharmacists contacted, 39 (3%) recruited 81 RA patients. The proportion of consultations including work-related discussions was 50% [95% confidence interval (CI) 42-58%] in the rheumatologist sample and 52% (95% CI 41-63%) in the patient sample. The most frequent subject of discussion (88%) was physical problems related to work in both samples. CONCLUSIONS: This is the first study to document the proportion of consultations where rheumatologists and their RA patients discuss work. Both specialists and patients reported that work was discussed in one in every two consultations.
25683368 Clinical practice guidelines for the management of pregnancy in women with autoimmune rheu 2015 Sep BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.
27237822 Nanomedicine for Intra-Articular Drug Delivery in Rheumatoid Arthritis. 2016 Rheumatoid arthritis is characterized by chronic inflammation within the joint. Recent developments in the understanding of inflammation have led to an increased interest in the use of nanomedicine in the treatment and diagnosis of rheumatoid arthritis. The ability of nanomedicine, such as nanoparticles, to permeate into and/or retain within the inflamed joint after intravenous and/or intra-articular administration has proven to be beneficial in improving rheumatoid arthritis therapy while reducing systemic exposure of patients to potentially toxic anti-arthritic drugs. This review aims at explaining the major applications of nanomedicine in rheumatoid arthritis treatment and diagnosis.
25228459 Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis 2015 Apr The association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003-December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5 %), TNF-α inhibitor exposure was considered a 'possible' cause. A majority of the 'probable cases' in JRA were reported with etanercept (40 patients, 90.91 %). There were no 'definite' cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.
25832859 Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy 2015 Oct OBJECTIVE: To evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients. METHODS: Patients who had completed 24 weeks of TCZ-SC (162 mg/2 weeks) or TCZ-IV (8 mg/kg/4 weeks) monotherapy in the double-blind period of the MUSASHI study were enrolled in an 84-week open-label extension period. All received TCZ-SC (162 mg/2 weeks) monotherapy. Effects of the IV to SC switch were evaluated at week 36 (12 weeks after switching). RESULTS: Overall, 319 patients received ≥1 dose of TCZ-SC during the open-label extension period; 160 switched from TCZ-IV to TCZ-SC (TCZ IV/SC) and 159 continued TCZ-SC (TCZ SC/SC). Disease Activity Score in 28 joints using the erythrocyte sedimentation rate clinical remission rates were 62.5% (100 of 160) for TCZ IV/SC and 50.0% (79 of 158) for TCZ SC/SC at week 24, and were maintained at 62.5% (100 of 160) and 57.0% (90 of 158), respectively, at week 36. In the TCZ IV/SC group, 9% of patients (9 of 100) who had achieved remission at week 24 could not maintain remission at week 36. In TCZ IV/SC patients weighing ≥70 kg, the percentage with a sufficient serum TCZ concentration (≥1 μg/ml) decreased from 90.9% (10 of 11) at week 24 to 45.5% (5 of 11) at week 36. Overall safety profiles were similar in TCZ IV/SC and TCZ SC/SC except for mild injection site reactions in TCZ IV/SC. CONCLUSION: Efficacy is adequately maintained in most patients switching from TCZ-IV (8 mg/kg/4 weeks) to TCZ-SC (162 mg/2 weeks) monotherapy. Patients receiving TCZ-IV can switch to TCZ-SC without serious safety concerns. Clinical efficacy may be reduced after switching in some patients with high body weight.
24817415 Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis 2015 Sep OBJECTIVES: Immunological events in the lungs might trigger production of anti-citrullinated protein antibodies during early rheumatoid arthritis (RA). We investigated the presence of shared immunological citrullinated targets in joints and lungs of patients with RA. PATIENTS AND METHODS: Proteins extracted from bronchial (n=6) and synovial (n=7) biopsy specimens from patients with RA were investigated by mass spectrometry-based proteomics. One candidate peptide was synthesised and used to investigate by ELISA the presence of antibodies in patients with RA (n=393), healthy controls (n=152) and disease controls (n=236). HLA-DRB1 shared epitope (SE) alleles were detected in patients with RA. RESULTS: Ten citrullinated peptides belonging to seven proteins were identified, with two peptides shared between the synovial and bronchial biopsy samples. Further analysis, using accurate mass and retention time, enabled detection of eight citrullinated peptides in synovial and seven in bronchial biopsy specimens, with five peptides shared between the synovial and bronchial biopsy specimens. Two citrullinated vimentin (cit-vim) peptides were detected in the majority of synovial and lung tissues. Antibodies to a synthesised cit-vim peptide candidate (covering both cit-vim peptides identified in vivo) were present in 1.8% of healthy controls, 15% of patients with RA, and 3.4% of disease controls. Antibodies to cit-vim peptide were associated with the presence of the SE alleles in RA. CONCLUSIONS: Identical citrullinated peptides are present in bronchial and synovial tissues, which may be used as immunological targets for antibodies of patients with RA. The data provide further support for a link between lungs and joints in RA and identify potential targets for immunity that may mediate this link.
27105880 Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review an 2016 Aug IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29-4.72, P = 0.006, I (2) 77 % and OR 2.94, 95 % CI 1.37-6.28, P = 0.005, I (2) 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1-6.89, P = 0.05, I (2) 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94-1.61, P = 0.13, I (2) = 0 % and OR 1.28, 95 % CI 0.57-2.88, P = 0.55, I (2) = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.
27861472 [Rheumatoid arthritis (RA) disease activity predicts function of ABCB1 (P-gp) and ABCG2 (B 2016 Nov BACKGROUND: P-gp and BCRP1 are transporter proteins that may confer drug resistance. OBJECTIVE: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity. METHODS: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry. Percentage of lymphocytes able to extrude substrates for P-gp and BCRP1 were recorded in the presence/absence of selective inhibitors. Informed consent was obtained. Descriptive statistics and linear regression model were applied. RESULTS: Active patients had higher efflux function of both transporters than inactive patients: median (25-75 IQR) P-gp of 7.1% (1.4-29.3) vs. 1.6% (0.7-3.5), p = 0.02 and BCRP1 of 6.2% (1.3-22.4) vs. 1.3% (0.7-2), p = 0.007. At baseline, disease activity was the only predictor of both transporter functions. At follow-up, changes in disease activity correlated with shift in P-gp (r = 0.35, p = 0.07) and BCRP1 (r = 0.33, p=0.09) function. CONCLUSIONS: Patients with active rheumatoid arthritis had a higher efflux function of P-gp and BCRP1 compared to inactive patients. The behavior of P-gp and BCRP1 appeared to be conditioned by disease activity.