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ID PMID Title PublicationDate abstract
29489833 Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages o 2018 Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.
29558044 Efficacy and safety of golimumab as add-on therapy to standard disease-modifying antirheum 2018 Apr BACKGROUND: The GO-MORE study was an open-label, multinational, prospective study that investigated the efficacy and safety of adding golimumab to synthetic disease-modifying antirheumatic drugs (sDMARDs) in patients with active rheumatoid arthritis (RA). OBJECTIVES: The aim of this study was to assess the efficacy and safety of golimumab add-on therapy in the Polish subpopulation of the GO-MORE study. MATERIAL AND METHODS: Patients were administered 50 mg subcutaneous doses of golimumab once a month for 6 months, while continuing therapy with sDMARDs and/or glucocorticoids (GCS). The primary clinical endpoint was the proportion of patients with moderate or good European League Against Rheumatism (EULAR) response based on the 28-joint disease activity score (DAS28) erythrocyte sedimentation rate (ESR) after 6 months. RESULTS: The Polish subpopulation (129 patients) was similar to the overall study population (3,280 patients) with regard to age, sex, mean baseline DAS28, inflammatory markers, average methotrexate dose, and GCS use; however, they had a longer disease duration (median: 6.04 vs 4.9 years) and more Polish patients (85.9% vs 78.7%) had high disease activity (DAS28-ESR ≥3.2). At 6 months, 84.5% of Polish patients showed good or moderate EULAR response, 26.4% had low disease activity and 17.1% were in clinical remission, compared with 82.9%, 37.4% and 23.9%, respectively, in the overall study population. Golimumab safety profile was consistent with previous studies and comparable to the overall study population. CONCLUSIONS: The addition of golimumab to sDMARD therapy in Polish RA patients showed good or moderate EULAR DAS28-ESR response in 84.5% of patients, mirroring the overall study population.
29388193 EOMES-positive CD4(+) T cells are increased in PTPN22 (1858T) risk allele carriers. 2018 Apr The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4(+) T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation. Moreover, the protein expression of the T-box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4(+) T cells. There was no difference in the frequency of other CD4(+) T-cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES(+) CD4(+) T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4(+) T cells and identify EOMES(+) CD4(+) T cells as a relevant T-cell subset in RA pathogenesis.
30046600 The Expansion of Myeloid-Derived Suppressor Cells Is Associated with Joint Inflammation in 2018 INTRODUCTION: We investigated the proportion of myeloid-derived suppressor cells (MDSCs) and their subsets in patients with rheumatic diseases and clarified the association between these cells and the patient clinical data. METHODS: Patients with rheumatic diseases and healthy controls were recruited. The clinical characteristics were obtained. The MDSCs and their subsets were marked with fluorescently labelled antibodies and were then analyzed with flow cytometry. RESULTS: The patients included 31 with RA, 21 with AS, 14 with OA, 11 with SLE with arthritis, 13 with SLE without arthritis, 9 with Gout, 10 with HUA, and 25 healthy controls. The proportions of MDSCs, M-MDSCs, and G-MDSCs were higher in patients with RA than in healthy controls (6.56±6.77% versus 1.46±0.96%, 2.52±3.81% versus 0.35±0.35%, and 1.13±1.64% versus 0.18±0.14%; p<0.001). The same increased cells were also found in other patients. The proportions of MDSCs and M-MDSCs were mostly correlated with the patient's joint inflammation indexes and the disease activity. When other cell subsets were adjusted, the increased risk of arthritis was also obtained for M-MDSCs (adjusted OR=5.772; p=0.031). CONCLUSIONS: The expansion of MDSCs and their subsets was correlated with the disease activity and joint inflammation in patient with different rheumatic diseases. The proportion of M-MDSCs was associated with the risk of arthritis in those populations.
29968101 [S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. 2018 Aug BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.
29851858 Identification of key genes in rheumatoid arthritis and osteoarthritis based on bioinforma 2018 Jun Rheumatoid arthritis (RA) and osteoarthritis (OA) comprise the most common forms of arthritis. The aim of this study was to identify differentially expressed genes (DEGs) and associated biological processes between RA and OA using a bioinformatics approach to elucidate their potential pathogenesis.The gene expression profiles of the GSE55457 datasets, originally produced through use of the high-throughput Affymetrix Human Genome U133A Array, were downloaded from the Gene Expression Omnibus (GEO) database. The GSE55457 dataset contains information from 33 samples, including 10 normal control (NC) samples, 13 RA samples, and 10 OA samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed to identify functional categories and associated molecular and biochemical pathways, respectively, for the identified DEGs, and a protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape software.GO and KEGG results suggested that several biological pathways (ie, "immune response," "inflammation," and "osteoclast differentiation") are commonly involved in the development of both RA and OA, whereas several other pathways (eg, "MAPK signaling pathway," and "ECM-receptor interaction") presented significant differences between these disorders.This study provides further insights into the underlying pathogenesis of RA and OA, which may facilitate the diagnosis and treatment of these diseases.
29392511 Comparative efficacy and safety of biosimilar adalimumab and originator adalimumab in comb 2018 May We aimed to assess the relative efficacy and safety of biosimilar adalimumab and originator adalimumab plus methotrexate (MTX) compared to those of placebo plus MTX in patients with active rheumatoid arthritis (RA) who showed an inadequate response to MTX. We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of biosimilar + MTX and adalimumab + MTX versus placebo + MTX (MTX group) in patients with active RA despite treatment with MTX. A total of eight RCTs involving 2543 patients met the inclusion criteria. The ACR20 response rate was significantly higher in the biosimilar + MTX (odds ratio [OR] 2.91, 95% credible interval [CrI] 1.57-5.74) and adalimumab + MTX (OR 2.80, 95% CrI 1.81-4.46) groups than in the MTX group, with no difference in the ACR20 response rate between the biosimilar + MTX and adalimumab + MTX groups. Biosimilar + MTX had the highest probability of being the best treatment in terms of the ACR20 response rate (surface under the cumulative ranking curve [SUCRA] = 0.7896), followed by adalimumab + MTX (SUCRA = 0.7082) and MTX (SUCRA = 0.0022). The ACR50 and ACR70 response rates showed a distribution pattern similar to that of the ACR20 response rate. Safety based on the number of serious adverse events did not differ significantly among the three interventions in the follow-up period of 12 to 24 weeks. Biosimilar and originator adalimumab, in combination with MTX, represent an effective intervention for active RA despite treatment with MTX. No significant difference was found between biosimilar and originator adalimumab in terms of efficacy and safety. However, follow-up in RCTs is short and not all safety outcomes can be assessed in RCTs. Thus, additional long-term evaluations are needed.
30570241 Inflammatory markers predict insulin sensitivity in active rheumatoid arthritis but not in 2018 Dec 20 Whether the insulin resistance commonly observed in patients with inflammatory arthritis is a disease-specific feature and/or is limited to a disease phase (i.e., it occurs only during phases of high disease activity) is unknown. Fifty-three rheumatoid arthritis (RA) and 44 psoriatic arthritis (PsA) patients were recruited consecutively along with 194 controls matched for age, sex and body mass index for a case-control study. All underwent an oral glucose tolerance test, the results of which were analysed to derive the following indexes: homeostatic model of insulin resistance (HOMA-IR), insulin sensitivity index (ISI) and early insulin sensitivity index (EISI). These data were related to anthropometric, clinical and laboratory findings. Metabolic parameters of patients and controls were similar. Neither inflammatory markers nor disease activity scores were related to glucose metabolism for the generality of RA and PsA patients; however, by restricting the analysis to the subset of RA patients with residual disease activity, an association emerged between erythrocyte sedimentation rate, on the one hand, and fasting insulin (β=0.46, p=0.047) and HOMA-IR (β=0.44, p=0.02), on the other. Moreover, C-reactive protein (CRP) levels were associated with plasma glucose and insulin levels measured 120 min after the glucose load (β=0.91, p=0.0003 and β=0.77, p=0.0006, respectively); ISI and EISI were predicted by CRP (β=-0.79, p=0.0006; β=-0.80, p=0.0001, respectively). The same did not hold true for PsA patients. The association between systemic inflammation and insulin resistance indexes is a feature of RA with residual disease activity, not a universal feature of inflammatory arthritides.
29737371 Efficacy and safety of interleukin-1 antagonists in rheumatoid arthritis: a systematic rev 2018 Aug Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017. The American College of Rheumatology 20% (ACR20) improvement was the primary efficacy outcome measure. Total number of adverse drug events, serious adverse drug events, total treatment withdrawals, and treatment-related withdrawals were safety outcome measures. Ten studies were included in this review. One study did not fulfil quantitative criteria and was assessed qualitatively. Six clinical trials and three extension studies were included in meta-analysis. Patients treated with anakinra are 42% more likely to have ACR20 response than patients without IL-1Ra (pooled RR 1.42; 95% CI 1.01, 2.00). Patients on 30-150 mg anakinra have lower Health Assessment Questionnaire (HAQ) score than patients without IL-1Ra (SMD - 0.28; 95% CI - 0.53, - 0.03). The inflammatory marker erythrocyte sedimentation rate (ESR) was significantly lower among patients treated with 30-150 mg anakinra (SMD - 0.44; 95% CI - 0.65, - 0.23). Patients on anakinra have a 34% more risk of treatment-related withdrawal than placebo. The other parameters were not found to be statistically significant. Anakinra has a significant improvement in ACR20, HAQ, and ESR. The ACR20 response is maintained after 48 weeks of treatment. Anakinra shows higher episodes of treatment-related withdrawals than placebo.
30299241 Efficacy of tocilizumab monotherapy after response to combined tocilizumab and methotrexat 2019 May OBJECTIVES: The aim of the JUST-ACT study was to assess whether the add-on effect of tocilizumab (TCZ) to background methotrexate (MTX) observed in MTX-inadequate responders with active rheumatoid arthritis (RA), would be sustained when MTX is withdrawn. METHODS: A double-blind, parallel-group, phase 3 study in biologic-naïve RA patients with a disease activity score 28 (DAS28)>3.2 despite MTX which were treated with TCZ+MTX for an initial 16-week period. Patients who at week 16 achieved low disease activity (LDA) (DAS28≤3.2) were randomised to continue with TCZ+MTX or switch to TCZ + placebo (PBO) for an additional 12 weeks. The primary endpoint was the change in DAS28-ESR from the randomisation at week 16 to week 28. Non-inferiority was confirmed if the upper limit of the two-sided 95%CI for the treatment difference between TCZ+MTX and TCZ monotherapy groups was lower than the selected non-inferiority margin of 0.6. RESULTS: 261 patients completed the first 16 weeks of TCZ+MTX treatment and 165 were randomised (83 to TCZ+MTX and 82 to TCZ+PBO). For the primary endpoint, the adjusted treatment difference (95% CI) in mean change of DAS28-ESR was -0.06 (-0.40 to 0.27), and therefore the non-inferiority of switching to TCZ monotherapy versus continuing with TCZ+MTX was demonstrated. In both treatment groups, the percentage of patients in clinical remission from 16 to 28 weeks was similar as were the improvements in disease activity, functional disability and quality of life. CONCLUSIONS: In MTX non-responder patients achieving LDA with TCZ+MTX, switching to TCZ monotherapy is non-inferior to continuing the combination.
29676105 [Effects of Tongbi capsule on joint lesions in rabbits with rheumatoid arthritis]. 2018 Mar The purpose of this experiment is to observe the effects of Tongbi capsule on joint lesions in rabbit with rheumatoid arthritis induced by ovalbumin and explore the mechanism in order to provide reference for clinical application of Tongbi capsule. Rheumatoid arthritis in rabbits was induced by subcutaneous injection of emulsions of ovalbumin and Freund's complete adjuvant and intra articular injection of ovalbumin. After successful modeling, 30 New Zealand rabbits with arthritis were randomly divided into model control group, the high, medium and low dose groups of Tongbi capsule (90, 45, 22.5 mg·kg⁻¹) and prednisone group (5 mg·kg⁻¹). Another six normal rabbits were used as normal control group. After 24 hours of modeling, the rabbits in Tongbi capsule groups received intragastric (i.g.) administrations of Tongbi capsule at 90, 45, 22.5 mg·kg⁻¹·d⁻¹, and the rabbits of prednisone group received i.g. administrations of prednisone at 5 mg·kg⁻¹·d⁻¹ for 2 weeks. The rabbits in normal and model groups received the same volume of distilled water at the same time. The swelling degree of rabbit knee joint and local skin temperature were observed daily. After two weeks of administration, pathological changes of rabbit knee joint were examined by magnetic resonance imaging (MRI); the morphological changes of articular cartilage and synovial membrane were observed by microscope; and the contents of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme linked immunosorbent assay (ELISA).The results showed that 24 h after modeling, the knee joints of the rabbits were swollen, with red or dark redlocal skin, and fever, elevated local skin temperature and increased diameters of knee joints. Two weeks after modeling, the swelling of rabbit knee joints was obvious in model group; the joint cavities were filled with purulent fluid; joint synovial membranes were obviously thickened, and even joint cavities were fibrotic and cartilage surfaces showed slight defect; the surface of articular cartilage was obvious fibrosis; synovial epithelial cell proliferation was obvious and accompanied by extensive inflammatory cell infiltration; the levels of IL-1 and TNF-α were significantly higher as compared with those seen in model rabbits (P<0.05, P<0.01). After 1 and 2 weeks of administration, knee joint diameters and local skin temperatures were smaller or lower than thosein model group (P<0.05, P<0.01); The lesions of joint cartilage and synovial of all rabbits in each group were less than those in model group; IL-1 and TNF-α levels in serum were also lower than those in model group (P<0.05, P<0.01). The results reveal that high and medium doses of Tongbi capsule can suppress rheumatoid arthritis induced by ovalbumin in rabbits, reduce joint swelling, inhibit synovial epithelial and fiber hyperplasia and inflammatory cell infiltration, and alleviate articular cartilage damage. The mechanism may be associated with decreasing IL-1 and TNF-α levels in serum.
30335822 Tyro3/Axl/Mertk-deficient mice develop bone marrow edema which is an early pathological ma 2018 Rheumatoid arthritis is an auto-immune disease of the synovial joints, hallmarked by chronic inflammation and subsequent progressive tissue destruction. TYRO3, AXL and MER (gene name Mertk) (TAM) receptors are part of a negative feedback signaling system in the immune reaction and mediate efferocytosis thereby tempering the inflammatory process. We have shown that Axl-/- and Mertk-/- mice develop more severe arthritis whereas activating these receptors by overexpressing their ligands Pros1 and Gas6 ameliorates arthritis. Mice genetically ablated for the three genes of the TAM receptor family Tyro3/Axl/Mertk (TAM triple knock-out or TKO) have been described to spontaneously develop macroscopic signs of arthritis. In this study we aimed to analyze arthritis development in TAM TKO mice histologically to determine the extent and sequence of pathological changes in the joint. Ankle joints of three different age groups, adolescence (14 weeks), mature adult (34 weeks) and middle-age (52 weeks), of TAM TKO or wild-type mice were examined macroscopically, histologically and immunohistochemically. Surprisingly, until the age of 52 weeks, none of the mice examined developed spontaneous macroscopic signs of arthritis. There was no synovial inflammation nor any signs of damage to the cartilage or bone. However, bone marrow edema was observed in TAM TKO mice in the two latter age groups. The infiltrate in the bone marrow was characterized by both myeloid cells and lymphocytes. This study showed that TAM TKO mice developed a pre-stage (pre-clinical phase) of arthritis marked by bone marrow edema.
29871962 Severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced 2018 Jun 5 Methotrexate is one of the most commonly used drugs in autoimmune disorders like rheumatoid arthritis. Gastrointestinal symptoms like nausea and stomatitis, skin rashes, alopecia, central nervous system symptoms like headache and confusion, hepatotoxicity and myelosuppression are some of the adverse effects. However, low oral doses on a weekly basis seldom show any signs of toxicity. Leucovorin or folinic acid is given along with methotrexate as rescue to reduce the toxic effects like bone marrow suppression. Non-steroidal anti-inflammatory drugs, like aceclofenac, are also used in chronic inflammatory conditions like rheumatoid arthritis and osteoarthritis. Nephrotoxicity is one of the adverse effects of both methotrexate and non-steroidal anti-inflammatory drugs; and its combined administration should be done with caution. This is a case of an elderly woman, a known case of rheumatoid arthritis, who presented in severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced acute kidney injury.
30538031 Platelet-derived microparticles generated in vitro resemble circulating vesicles of patien 2019 Feb Patients with rheumatoid arthritis (RA) have increased amount of platelet-derived microparticles (PMPs) positive for citrullinated peptides (CPs) that form immune complexes (PMPs-ICs). Monocytes are important inflammatory mediators that play a role in the clearance of PMPs-ICs. We aimed to generate PMPs-ICs in vitro and determine its effect on monocytes from patients with RA and healthy individuals (HI). PMPs from patients showed platelet markers, mitochondria content, and phosphatidylserine exposure similar to PMPs from HI. However, patients had a higher frequency of IgG+ and CPs+ vesicles than HI. PMPs-ICs generated in vitro were similar to the circulating vesicles of patients with respect to IgG- and CPs-positivity. PMPs-ICs induced pro-inflammatory cytokines and CX3CR1 expression in monocytes from HI, and IL-10 and CD36 upregulation in monocytes from patients. These results suggest that PMPs-ICs induce activation of monocytes, with a pro-inflammatory response in HI and a more tolerant response in cells of patients with RA.
30039267 The association between 10-year fracture risk by FRAX and osteoporotic fractures with dise 2018 Oct As rheumatoid arthritis (RA) is an independent risk factor for osteoporotic fractures, the severity of disease activity may correlate with fracture risk. Our objectives were to determine the prevalence of major osteoporotic and hip fractures in patients with RA and to identify the factors related to their 10-year probabilities. This study enrolled 232 patients with RA, aged 40-90 years, who participated in the Siriraj RA Cohort in 2016 and 2017. Demographic data, disease activity scores 28 (DAS28), and health assessment questionnaires (HAQ) were collected. All participants were evaluated for asymptomatic vertebral fractures by thoracolumbar spine radiography. The osteoporotic fracture risks were determined using the fracture risk assessment tool (FRAX). Most subjects were postmenopausal women in their sixth decade; the median disease duration was 12.95 years. Forty-six percent of patients had osteoporotic fractures, and most (87%) were vertebral fractures. Eighty-one patients had asymptomatic vertebral compression fractures. Of those, 57%, 25%, and 18% had low, moderate, and high 10-year probabilities of major osteoporotic fractures, respectively, while 51%, 34%, and 15% had low, moderate, and high 10-year probabilities of hip fractures, respectively. Factors significantly associated with the 10-year probabilities of major osteoporotic and hip fractures were disease duration (p 0.017, 0.009), menopause duration (p < 0.001 both), cumulative disease activity (DAS28; p 0.004, 0.029), and cumulative functional disability (HAQ; p < 0.001 both). Moderate to high 10-year probabilities of major osteoporotic and hip fractures are common in RA. Cumulative disease severity is a high risk for osteoporotic fractures.
29704913 Effects of oral contraceptives on rheumatoid arthritis in Korean menopausal women: A natio 2018 Jun Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with a multifactorial etiology. The higher prevalence of RA in women than in men may originate from differences in sex hormone levels or types. Ethnicity may interact with hormonal factors to produce various observed differences in the prevalence of RA. Oral contraceptives (OCs) are a source of exogenous sex hormones and can affect the prevalence of RA. We investigated the effects of OCs on RA in Korean menopausal women using a national data set. Data were collected from a cross-sectional study of 8789 eligible participants who completed the 2008-2012 Korea National Health and Nutrition Examination Survey. To balance the distribution of baseline characteristics between those participants who had ever used OCs and those who had not, we employed propensity score matching to adjust for differences. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the effects of OCs on the incidence of RA. The development of RA in Korean women rapidly increased during the perimenopause. After propensity score matching, the use of OCs was associated with RA (OR 1.24, 95% CI 1.01-1.51, P = 0.04). However, hormone replacement therapy (HRT) was not associated with RA regardless of whether OCs had been used (OR 0.80, 95% CI 0.62-1.04, P = 0.09, and OR 1.00, 95% CI 0.66-1.52, P = 0.99, respectively). Our findings suggest that factors associated with sex hormones influence the prevalence of RA.
29468340 Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission 2018 Jun The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.
29720237 Factors associated with physicians' prescriptions for rheumatoid arthritis drugs not fille 2018 May 2 BACKGROUND: This study estimated the extent and predictors of primary nonadherence (i.e., prescriptions made by physicians but not initiated by patients) to methotrexate and to biologics or tofacitinib in rheumatoid arthritis (RA) patients who were newly prescribed these medications. METHODS: Using administrative claims linked with electronic health records (EHRs) from multiple healthcare provider organizations in the USA, RA patients who received a new prescription for methotrexate or biologics/tofacitinib were identified from EHRs. Claims data were used to ascertain filling or administration status. A logistic regression model for predicting primary nonadherence was developed and tested in training and test samples. Predictors were selected based on clinical judgment and LASSO logistic regression. RESULTS: A total of 36.8% of patients newly prescribed methotrexate failed to initiate methotrexate within 2 months; 40.6% of patients newly prescribed biologics/tofacitinib failed to initiate within 3 months. Factors associated with methotrexate primary nonadherence included age, race, region, body mass index, count of active drug ingredients, and certain previously diagnosed and treated conditions at baseline. Factors associated with biologics/tofacitinib primary nonadherence included age, insurance, and certain previously treated conditions at baseline. The area under the receiver operating characteristic curve of the logistic regression model estimated in the training sample and applied to the independent test sample was 0.86 and 0.78 for predicting primary nonadherence to methotrexate and to biologics/tofacitinib, respectively. CONCLUSIONS: This study confirmed that failure to initiate new prescriptions for methotrexate and biologics/tofacitinib was common in RA patients. It is feasible to predict patients at high risk of primary nonadherence to methotrexate and to biologics/tofacitinib and to target such patients for early interventions to promote adherence.
29383454 Increased frequency of temporal acoustic window failure in rheumatoid arthritis: a manifes 2018 May Assessment of intracranial vessels includes transcranial Doppler (TCD). TCD performance requires intact temporal acoustic windows (TAW). Failure of TAW (TAWF) is present in 8-20% of people. There have been no reports on TAWF in rheumatoid arthritis (RA). Altogether, 62 female RA patients were included. Among them, 20 were MTX-treated and biologic-free, 20 received infliximab, and 22 tocilizumab. The controls included 60 non-RA women. TAWF, temporal bone thickness, and texture were determined by ultrasound and CT. BMD and T-scores of multiple bones were determined by DEXA. Several bone biomarkers were assessed by ELISA. In RA, 54.8% of the patients had TAWF on at least one side. Neither TAW could be identified in 34% of RA subjects. In contrast, only 20.0% of control subjects had TAWF on either or both sides (p < 0.001). In RA vs controls, 53.0 vs 2.9% of subjects exerted the trilayer, "sandwich-like" structure of TAW (p < 0.001). Finally, in RA vs controls, the mean temporal bone thickness values of the right TAW were 3.58 ± 1.43 vs 2.92 ± 1.22 mm (p = NS), while those of the left TAW were 4.16 ± 1.56 vs 2.90 ± 1.16 mm (p = 0.001). There was close association between TAWF, bone thickness, and texture (p < 0.05). These TAW parameters all correlated with age; however, TAW failure and texture also correlated with serum osteoprotegerin. TAW bone thickness inversely correlated with hip BMD (p < 0.05). TAWF, thicker, and heterogeneous temporal bones were associated with RA. These features have been associated with bone loss and OPG production. Bone loss seen in RA may result in OPG release and stimulation of bone formation around TAW.
30191608 miR-145 eliminates lipopolysaccharides-induced inflammatory injury in human fibroblast-lik 2018 Dec Recently, it has been accepted that miR-based therapy may be beneficial for rheumatoid arthritis (RA). This study aimed to evaluate the potential involvement of miR-145 in RA in vitro. The expression of miR-145 in the human fibroblast-like synoviocyte line MH7A was overexpressed by miR-mimic transfection, after which cells were subjected to lipopolysaccharides (LPS). Cell viability, apoptosis, and the release of pro-inflammatory cytokines were measured. The result showed that the apoptosis and the release of IL-1β, IL-6, IL-8, and TNF-α were significantly induced by LPS. Meanwhile, LPS treatment led to downregulation of miR-145. miR-145 overexpression in LPS-untreated MH7A cells had no impacts on cell apoptosis and inflammation. But, restoring miR-145 expression in LPS-stimulated cells by supplementation of a miR-145 mimic protected MH7A cells against LPS-induced apoptosis and inflammation. Furthermore, miR-145 overexpression in LPS-untreated MH7A cells slightly blocked the PI3K/ATK and mTOR pathways, whereas miR-145 overexpression in LPS-stimulated cells notably repressed the LPS-induced activation of PI3K/ATK and MAPK/mTOR pathways. Our study suggested that miR-145 protected MH7A cells against LPS-induced apoptosis and inflammation by inhibiting the PI3K/AKT and MAPK/mTOR pathways.