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ID PMID Title PublicationDate abstract
28473207 Quantification of cartilage oligomeric matrix protein (COMP) and a COMP neoepitope in syno 2017 Sep OBJECTIVE: To develop automated immunoassays for the quantification of Cartilage Oligomeric Matrix Protein (COMP) and a COMP neoepitope in synovial fluid and to investigate their diagnostic potential in different joint conditions. METHODS: Two sandwich immunoassays were developed for the quantification of COMP and a COMP neoepitope, using an automated analyser (IDS-iSYS, Immunodiagnostic Systems, Boldon, UK). Assay performance was evaluated in terms of sensitivity, recovery, linearity, and intra- and inter-assay precision. Clinical performance was evaluated by analysing synovial fluid from patients diagnosed with rheumatoid arthritis (RA), reactive arthritis (ReA), osteoarthritis (OA) or acute trauma (AT). RESULTS: Both automated assays showed good performance for all parameters tested. Quantification of these biomarkers showed the highest median values for Total COMP in the OA group, followed by the AT group, the ReA group, and the RA group. For the COMP neoepitope the AT group showed the highest median value, followed by the ReA group, the OA group, and the RA group. The ratio COMP neoepitope/Total COMP showed distinct differences between the patients groups, as well as between RA patients with slow or rapid progression of joint damage. CONCLUSIONS: The newly developed automated assays have a good technical performance, can reliably quantify different epitopes on the COMP molecule and show different levels of the two biomarkers in synovial fluid in patients with different joint diseases. The combination of these two assays, measuring their ratio, shows promise for early detection of patients with RA with different prognosis regarding progression of joint damage.
27781272 Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen a 2017 Jun BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). MATERIAL AND METHODS: Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. RESULTS: All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. CONCLUSION: In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of periodontitis.
28487948 Effect of aloe‑emodin on the proliferation and apoptosis of human synovial MH7A cells; a 2017 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia. Methotrexate (MTX), an antifolate derivative, is used for the treatment of RA, as it exerts antiproliferative efftects on lymphocytes and synovial cells. Aloe‑emodin (AE) is a primary component of anthraquinones in Aloe vera and exerts antiproliferative and apoptotic effects on various tumor cells. In the present study, the effect of AE on the proliferation and apoptosis of MH7A human RA synovial cells was examined. In addition, the effect of AE was compared with that of the established RA therapeutic MTX. MH7A cells were incubated with 5, 10, 20 or 40 µM AE, or 0.01, 0.05, 0.1 or 1 µM MTX, for 24, 48 or 72 h. Subsequently, total cell numbers were assessed using trypan blue staining and Cell Counting kit‑8. Furthermore, MH7A cells incubated with AE or MTX for 48 h were evaluated for apoptosis following Annexin V/propidium iodide (PI) staining, and for cell cycle distribution following PI staining. The results indicated that ≥10 µM AE and ≥0.05 µM MTX effectively decreased the numbers of viable MH7A cells. In addition, 40 µM AE and 1 µM MTX induced apoptosis in MH7A cells. Cell cycle analysis revealed that ≥20 µM AE induced G2/M phase arrest, whereas ≥0.1 µM MTX induced S phase arrest. These observations suggested that AE treatment inhibited the growth of MH7A cells by arresting the cell cycle at a different checkpoint compared with MTX treatment. Thus, AE may be a potential therapeutic agent for the treatment of RA, and may be complimentary to MTX, based on its antiproliferative effect on synovial cells.
29246162 Use of a baseline risk score to identify the risk of serious infectious events in patients 2017 Dec 15 BACKGROUND: The risk of serious infectious events (SIEs) is increased in patients with rheumatoid arthritis (RA). The aim of this study was to develop an age-adjusted comorbidity index (AACI) to predict, using baseline characteristics, the SIE risk in patients with RA treated with certolizumab pegol (CZP). METHODS: Data of CZP-treated patients with RA were pooled from the RAPID1/RAPID2 randomized controlled trials (RCT CZP) and their open-label extensions (All CZP). Predictors of the first SIE were examined using multivariate Cox models. The AACI was developed by assigning specific weights to patient age and comorbidities on the basis of relative SIE risk. SIE rates were predicted using AACI score and baseline glucocorticoid use, and they were compared with observed rates. The percentage of patients in each SIE risk group achieving low disease activity (LDA)/remission was examined at 1 year of treatment. RESULTS: Among 1224 RCT CZP patients, 40 reported ≥ 1 SIE (incidence rate [IR] 5.09/100 patient-years [PY]), and 201 of 1506 All CZP patients reported ≥ 1 SIE (IR 3.66/100 PY). Age ≥ 70 years, diabetes mellitus, and chronic obstructive pulmonary disease/asthma made the greatest contributions to AACI score. SIE rates predicted using AACI and glucocorticoid use at baseline showed good agreement with observed SIE rates across low-risk and high-risk groups. At 1 year, more high-risk All CZP patients than low-risk All CZP patients reported SIEs (IR 8.4/100 PY vs. IR 3.4/100 PY). Rates of LDA/remission were similar between groups. CONCLUSIONS: AACI and glucocorticoid use were strong baseline predictors of SIE risk in CZP-treated patients with RA. Predicted SIE risk was not associated with patients' likelihood of clinical response. This SIE risk score may provide a valuable tool for clinicians when considering the risk of infection in individual patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00152386 (registered 7 September 2005); NCT00160602 (registered 8 September 2005); NCT00175877 (registered 9 September 2005); and NCT00160641 (registered 8 September 2005).
28538163 Metabolic signatures of T-cells and macrophages in rheumatoid arthritis. 2017 Jun In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors. Here, we use the model system of rheumatoid arthritis (RA) to discuss immunometabolism from the vantage point of T-cells and macrophages that encounter fundamentally different metabolic stress scenarios in the RA host. We outline the general principle that both insufficient nutrient supply, as well as nutrient excess generate cellular stress responses and guide immune function. ATP(low), NADPH(high), ROS(low) T-cells hyperproliferate and are forced into premature senescence. ATP(high), ROS(high) macrophages dimerize the glycolytic enzyme pyruvate kinase to amplify STAT3-dependent inflammatory effector functions. A corollary of this model is that simple nutraceutical interventions will be insufficient to re-educate the immune system in RA. Instead, interference with cell-type-exclusive and differentiation-stage-dependent metabolic setpoints will be needed to reprogram arthritogenic pathways.
28461642 Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumato 2017 Jul OBJECTIVE: The aims of this study were to evaluate whether treatment with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) affects the risk of developing severe extraarticular rheumatoid arthritis (ExRA) manifestations and to investigate potential predictors for developing ExRA. METHODS: A dynamic community-based cohort of patients with RA was studied (n = 1977). Clinical records were reviewed and cases of severe ExRA were identified. Information on exposure to TNF inhibitors was obtained from a regional register. Exposure to TNF inhibitors was analyzed in a time-dependent fashion and the incidence of severe ExRA in exposed patients was compared with the incidence in unexposed patients. Cox regression models were used to assess potential predictors of severe ExRA. RESULTS: During treatment with TNF inhibitors, there were 17 patients with new onset of severe ExRA in 2400 person-years at risk (PY; 0.71/100 PY, 95% CI 0.41-1.13) compared with 104 in 15,599 PY (0.67/100 PY, 95% CI 0.54-0.81) in patients without TNF inhibitors. This corresponded to an incidence rate ratio of 1.06 (95% CI 0.60-1.78). The age- and sex-adjusted HR for ExRA in anti-TNF-treated patients was 1.21 (95% CI 1.02-1.43), with similar findings in models adjusted for time-dependent Health Assessment Questionnaire and propensity for anti-TNF treatment. Male sex, positive rheumatoid factor (RF), long disease duration, and greater disability were predictors for ExRA. CONCLUSION: This study suggests that patients treated with TNF inhibitors are at a slightly increased risk of developing severe ExRA. RF-positive patients with disabling disease of long duration were more likely to develop severe ExRA.
28538835 Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with 2017 May 18 Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.
28099218 Perceptions in Rheumatoid Arthritis: Comparative Study Between Patients and Their Close Fa 2017 Aug OBJECTIVE: To compare perceptions of patients with rheumatoid arthritis (RA) to those of their families regarding pain and subjective experience of the disease. METHODS: It was a monocentric study, including 120 RA patients (according to the American College of Rheumatology criteria). The questionnaires were developed during meetings of RA patients, rheumatologists, and methodologists while referring to the literature. The patient questionnaire comprised 22 items organized in 4 sections: pain, perceived experience of the disease, activity restrictions, and help received. Concordance among patients, family, and friends replies was evaluated using the kappa coefficient. RESULTS: The mean age was 42 ± 12 years with female predominance 110 (91.7%). The family member was usually the spouse (46.3%). Joint pain was described by patients as spontaneous (98.3%), unpredictable (95.9%), and variable (95.1%). RA had negatively affected work-related activities (100%), recreational activities (98.4%), family life (87.6%), relationships with friends (77.7%), sexual activities (50.4%), plans for having children (47.1%), and intimate relationships (46.3%). Concordance between patients and family perceptions was mediocre for pain severity (kappa: 0.3) and main joint-pain characteristics, excellent for majority items of experience of the disease (kappa > 0.80). Family tended to underestimate pain severity and to overestimate negative effects of RA on patient's life. CONCLUSION: We found a good agreement between patients' and family members' perceptions. It is essential that any family support be in accordance with patients' needs. Our qualitative analysis objectified, in addition to a major physical impact of the disease, a negative psychosocial effect.
28884373 Prevalence of and factors associated with renal dysfunction in rheumatoid arthritis patien 2017 Dec This study was designed to determine the prevalence of renal dysfunction in rheumatoid arthritis (RA) patients and to identify factors associated with this complication. Between October 2014 and May 2015, we consecutively recruited RA patients at rheumatology sections of community hospitals in Japan. Each patient's absolute and body surface area (BSA)-indexed estimated glomerular filtration rate (eGFR) values were measured twice over a 3-month interval. Renal dysfunction was defined as absolute eGFR or BSA-indexed eGFR < 60. Albuminuria and hematuria were also recorded. Associations between renal dysfunction and possible risk factors were examined by multivariate logistic regression analyses. A total of 1908 outpatients with RA were included in this study. The prevalence of renal dysfunction based on absolute eGFR and BSA-indexed eGFR was 33.8 and 18.6%, respectively. Albuminuria was observed in 8.1% of this patient cohort, and the prevalence of hematuria was 7.5%. Advanced age (odds ratio [OR] 7.24, p < 0.001), female sex (OR 3.12, p < 0.001), hypertension (OR 2.22, p < 0.001), and obesity (OR 0.59, p < 0.001) were independently associated with the risk of absolute eGFR-based renal dysfunction. Advanced age (OR 5.19, p < 0.001) and hypertension (OR 3.05, p < 0.001) also had associations with BSA-indexed eGFR-based renal dysfunction. RA duration, stages, severity, and cumulative steroid dose were considered significant risk factors in univariate analyses, but their associations were less potent after adjustment for other covariates. Renal dysfunction is relatively common in RA patients and is mainly associated with advanced age and hypertension but not with RA-related factors.
28948414 CD147-mediated chemotaxis of CD4(+)CD161(+) T cells may contribute to local inflammation i 2018 Jan CD161 is used as a surrogate marker for Th17 cells, which are implicated in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the percentage, clinical significance, and CD98 and CD147 expression of CD4(+)CD161(+) T cells. The potential role of CD147 and CD98 in cyclophilin A-induced chemotaxis of CD4(+)CD161(+) T cells was analyzed. Thirty-seven RA patients, 15 paired synovial fluid (SF) of RA, and 22 healthy controls were recruited. The cell populations and surface expression of CD98 and CD147 were analyzed by flow cytometry. Spearman's rank correlation coefficient and multiple linear regression were applied to calculate the correlations. Chemotaxis assay was used to investigate CD4(+)CD161(+) T cell migration. We found that the percentage of CD4(+)CD161(+) T cells and their expression of CD147 and CD98 in SF were higher than in the peripheral blood of RA patients. Percentage of SF CD4(+)CD161(+) T cells was positively correlated with 28-Joint Disease Activity Score (DAS28). CD147 monoclonal antibody (HAb18) attenuated the chemotactic ability of CD4(+)CD161(+) T cells. An increased CD4(+)CD161(+) T cell percentage and expression of CD147 and CD98 were shown in RA SF. Percentage of SF CD4(+)CD161(+) T cells can be used as a predictive marker of disease activity in RA. CD147 block significantly decreased the chemotactic index of CD4(+)CD161(+) cells induced by cyclophilin A (CypA). These results imply that the accumulation of CD4(+)CD161(+) T cells in SF and their high expression of CD147 may be associated with CypA-mediated chemotaxis and contribute to local inflammation in RA.
28455828 Prevalence of hearing impairment in patients with rheumatoid arthritis, granulomatosis wit 2017 Jul Hearing loss in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), or rheumatoid arthritis (RA), is controversial. Many studies lack measurements of bone-conduction thresholds to sufficiently differentiate between sensorineural hearing loss and conductive hearing loss. In addition, many studies lack control groups or comparisons to an age-related normal hearing threshold. This study investigates hearing performance with an extended audiological battery using psychoacoustic and objective measures. A total of 22 adults with RA, 16 with GPA, 20 with SLE, and two age- and gender-matched control groups (n = 34 for GPA and RA and n = 42 for SLE) were included. Pure-tone hearing thresholds, speech perception in quiet and noise, tympanometry, and high-resolution otoacoustic emissions were assessed. GPA patients exhibited impaired pure-tone hearing compared to the control group, whereas SLE and RA patients did not. In GPA patients, a larger air-bone gap indicated conductive hearing loss. In addition, speech perception was reduced exclusively in GPA patients. A significant correlation was found between hearing loss and both the cumulative steroid dose and number of organ manifestations in GPA and SLE patients. Our data indicate that GPA and SLE patients are at moderate-to-high risk of conductive hearing loss. In contrast, RA patients are at low risk of disease-associated hearing loss.
28061847 Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. 2017 Jan 6 BACKGROUND: A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health. METHODS: This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA). RESULTS: In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction. CONCLUSIONS: A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.
28004435 Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervou 2017 Jun A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.
27429379 CHOROIDAL THICKNESS IN MULTISYSTEMIC AUTOIMMUNE DISEASES WITHOUT OPHTHALMOLOGIC MANIFESTAT 2017 Mar PURPOSE: To evaluate choroidal morphology and thickness at the posterior pole of individuals affected by multisystemic autoimmune diseases and without known ophthalmologic manifestations. METHODS: Retrospective cross-sectional study including 75 patients with autoimmune diseases (divided according to their specific disease) and 80 healthy controls. A spectral-domain optical coherence tomography using enhanced depth imaging was performed and choroidal thickness was measured in the center of fovea and at 500 μm intervals along a horizontal section. RESULTS: Lupus patients presented a thicker subfoveal choroid than controls (408.624 vs. 356.536, P < 0.001) and in all the other measurements (P < 0.001 to P = 0.003). Rheumatoid arthritis and other autoimmune diseases had an overall thinner choroid than controls (297.867 vs. 356.536 subfoveally, P = 0.004; P = 0.005-0.019 in other measurements). Results were adjusted for the covariates age (P = 0.007), spherical equivalent (P < 0.001), and systemic steroids dose (P = 0.004). Hypertension (P = 0.102), diabetes mellitus (P = 0.672), time since the beginning of therapy with hydroxychloroquine (P = 0.104) and its cumulative dose (P = 0.307), or use of other immunosuppressives (P = 0.281) had no influence on the mean choroidal thickness. No morphologic abnormalities were found. CONCLUSION: The choroid may be subclinically involved in autoimmune diseases. However, the choroidal response seems to differ depending on the autoimmune disease. Infiltrative mechanisms specific for lupus may justify the thickened choroid found in these patients.
28461643 Development and Validation of the OMERACT Rheumatoid Arthritis Magnetic Resonance Tenosyno 2017 Nov OBJECTIVE: To develop and validate a magnetic resonance imaging (MRI) tenosynovitis (TS) score for tendons at the wrist and metacarpophalangeal (MCP) joint levels in patients with rheumatoid arthritis (RA). METHODS: Axial T1-weighted precontrast and postcontrast fat-saturated MR image sets of the hands of 43 patients with RA initiating rituximab therapy were obtained at baseline and after 14, 26, 38, or 52 weeks. The MR images were scored twice by 4 readers. Nine tendon compartments of the wrist and 4 flexor tendon compartments at the MCP joints were assessed. Tenosynovitis was scored as follows: 0: No; 1: < 1.5 mm; 2: ≥ 1.5 mm but < 3 mm; 3: ≥ 3 mm peritendinous effusion and/or postcontrast enhancement. Intrareader and interreader intraclass correlation coefficients (ICC), smallest detectable change (SDC), percentage of exact and close agreement (PEA/PCA), and standardized response mean (SRM) were calculated. RESULTS: Intrareader and interreader ICC for status and change scores were very good (≥ 0.80) for total scores for all readers. Intrareader SDC was ≤ 3.0 and interreader SDC was < 2.0. The overall PEA/PCA intrareader and interreader agreements for change scores in all tendons were 73.8%/97.6% and 47.9%/85.0%, respectively. Average SRM was moderate for total scores and 60.5% of the patients had a tenosynovitis change score ≥ SDC. CONCLUSION: The TS score showed high intrareader and interreader agreement for wrist and finger tendons, with moderate responsiveness, and the majority of the patients showed a change above the SDC. This scoring system may be included as a component of the RAMRIS.
29116543 Remission assessment of rheumatoid arthritis in daily practice in China: a cross-sectional 2018 Mar The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. A total of 1945 patients with RA were included in the study. The proportions of patients who fulfilled the DAS28-ESR, CDAI, SDAI, and ACR/EULAR remission criteria were 10.90%, 6.17%, 5.04% , and 1.75%, respectively. Most patients had taken at least one disease-modifying anti-rheumatic drug (DMARD), and the most common prescriptions included leflunomide (LEF) and methotrexate (MTX). DMARD combined with botanics were the most common and dominant strategy for RA management (29.16%). Overall, 433 patients (22.27%) had at least one adverse event. Gastrointestinal adverse events (41.27%) were the most frequently reported events. The incidence of side effects in patients using biologics DMARDs (bDMARDs) was significantly lower than that in those taking MTX, LEF, or sulfasalazine (SSZ). The remission rate of RA disease activity, as assessed in Chinese clinical practice, was very low. Adverse effects of the medicine occurred in approximately one in five RA patients, with bDMARDs were demonstrated to be the medication with the lowest side effects.
28089978 Rituximab Retreatment in Rheumatoid Arthritis in a Real-life Cohort: Data from the CERERRA 2017 Feb OBJECTIVE: Several aspects of rituximab (RTX) retreatment in rheumatoid arthritis (RA) need to be further elucidated. The aim of this study was to describe the effect of repeated courses of RTX on disease activity and to compare 2 retreatment strategies, fixed-interval versus on-flare retreatment, in a large international, observational, collaborative study. METHODS: In the first analysis, patients with RA who received at least 4 cycles with RTX were included. In the second analysis, patients who received at least 1 RTX retreatment and for whom information about the strategy for retreatment was available were identified. Two retreatment strategies (fixed-interval vs on-flare) were compared by fitting-adjusted, mixed-effects models of 28-joint Disease Activity Score (DAS28) over time for first and second retreatment. RESULTS: A total of 1530 patients met the eligibility criteria for the first analysis. Significant reductions of mean DAS28 between the starts of subsequent treatment cycles were observed (at start of first treatment cycle: 5.5; second: 4.3; third: 3.8; and fourth: 3.5), suggesting improved response after each additional cycle (p < 0.0001 for all pairwise comparisons). A total of 800 patients qualified for the second analysis: 616 were retreated on flare and 184 at fixed interval. For the first retreatment, the fixed-interval retreatment group yielded significantly better results than the on-flare group (estimated marginal mean DAS28 = 3.8, 95% CI 3.6-4.1 vs 4.6, 95% CI 4.5-4.7, p < 0.0001). Similar results were found for the second retreatment. CONCLUSION: Repeated treatment with RTX leads to further clinical improvement after the first course of RTX. A fixed-interval retreatment strategy seems to be more effective than on-flare retreatment.
27440258 Serum tocilizumab trough concentration can be used to monitor systemic IL-6 receptor block 2017 Mar OBJECTIVES: To investigate the pharmacokinetics (PK) and dynamics of tocilizumab (TCZ) in daily practice. METHOD: An observational study of 66 consecutive RA patients treated with TCZ 8 mg/kg once every 4 weeks intravenously, monitored for 24 weeks. Spearman's rank test was used to investigate the correlation between TCZ concentration and C-reactive protein (CRP). Clinical improvement was assessed at week 24 using the Disease Activity Score in 28 joints (DAS28) compared to baseline, and its relationship with TCZ concentration was investigated using linear regression analyses. TCZ trough concentrations and anti-drug antibodies were measured using an enzyme-linked immunosorbent assay (ELISA) and antigen binding test, respectively. RESULTS: At baseline, 26 patients (39.4%) had a CRP level above 10 mg/L with a median (interquartile range, IQR) of 37.7 (21.9-49.7) mg/L. A TCZ concentration above 1 mg/L was sufficient to normalize CRP levels. Spearman's rank test showed a correlation coefficient of -0.460 (p < 0.0001). The TCZ concentration varied widely, with concentrations < 1 mg/L in 17-31% of patients, depending on the time point of measurement. Anti-TCZ antibodies were detected in one sample. Linear regression analyses showed a coefficient of 0.080 with a 95% confidence interval (CI) of 0.039-0.113 (p < 0.001) for the association between TCZ concentration and ΔDAS28. No confounders were identified. CONCLUSIONS: The TCZ standard regimen results in a wide variety of serum TCZ trough concentrations; this is mostly due to target binding and to a lesser extent to immunogenicity. The majority of patients obtained TCZ concentrations > 1 mg/L, which is sufficient for CRP normalization. Therefore, dose taper strategies might be possible in a substantial proportion of patients.
28516869 Recommendations for infectious disease screening in migrants to Western Europe with inflam 2017 Sep OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.
28511285 Association of Increased F4/80(high) Macrophages With Suppression of Serum-Transfer Arthri 2017 Sep OBJECTIVE: Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis. METHODS: Mice with Flip deleted in myeloid cells (Flip(f/f) LysM(c/+) mice) and littermate controls were used. Arthritis was induced by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by clinical score and change in ankle thickness, and joints were examined by histology and immunohistochemistry. Cells were isolated from the ankles and bone marrow of the mice and examined by flow cytometry, real-time quantitative reverse transcriptase-polymerase chain reaction, or Western blotting. RESULTS: In contrast to expectations, Flip(f/f) LysM(c/+) mice developed more severe arthritis early in the clinical course, but peak arthritis was attenuated and the resolution phase more complete than in control mice. Prior to the induction of serum-transfer arthritis, the number of tissue-resident macrophages was reduced. On day 9 after arthritis induction, the number of F4/80(high) macrophages in the joints of the Flip(f/f) LysM(c/+) mice was not decreased, but increased. FLIP was reduced in the F4/80(high) macrophages in the ankles of the Flip(f/f) LysM(c/+) mice, while F4/80(high) macrophages expressed an antiinflammatory phenotype in both the Flip(f/f) LysM(c/+) and control mice. CONCLUSION: Our observations suggest that reducing FLIP in macrophages by increasing the number of antiinflammatory macrophages may be an effective therapeutic approach to suppress inflammation, depending on the disease stage.