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ID PMID Title PublicationDate abstract
31659868 Quantitative tracking of inflammatory activity at the peak and trough plasma levels of tof 2019 Dec PURPOSE: To assess the capability of in vivo positron emission tomography (PET) using (18) F-fluorodeoxyglucose ((18) F-FDG) to quantify changes in inflammatory activity in response to tofacitinib, a Janus kinase (JAK) inhibitor, over a timeframe of a few hours to few days in a preclinical model of rheumatoid arthritis (RA). METHODS: Twenty-four mice with collagen-induced arthritis in the following groups were assessed: Group 1, where the changes in PET measures for the extremity joints were evaluated at the peak and trough plasma drug levels after administration of a single dose of tofacitinib (4 hours apart); Group 2, where joint PET measures were assessed before treatment and after 6 days of administration of a daily dose of tofacitinib; and group 3 (controls), where joint PET measures were derived from the same mice, 6 days apart. RESULTS: At about peak plasma levels of the drug after a single tofacitinib administration, there was a reduction in PET measures compared to pretreatment values, suggesting decreased inflammatory activity. These measures were equivalent to those obtained after 6 days of daily dosing by tofacitinib. However, PET measures at trough plasma levels of the drug from tofacitinib administration were significantly higher than those at peak plasma drug levels and equivalent to pretreatment measures. There were insignificant changes in PET measures for the control animals. CONCLUSION: (18) F-FDG PET can detect changes in inflammatory activity occurring in response to the JAK inhibitor tofacitinib: (a) during peak and trough plasma drug levels, that is within mere hours of treatment; and (b) over a span of days.
31015032 Nanomedicines for improved targetability to inflamed synovium for treatment of rheumatoid 2019 Jun 10 Owing to its intricate autoimmune pathophysiology and significant risks of progression to other rheumatic co-morbidities (i.e., osteoporosis and osteoarthritis), a plausible therapeutic regimen is mandatory for early-stage management of rheumatoid arthritis (RA). Nevertheless, the conventional therapeutic agents particularly the corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) have shown grander success in the treatment of RA; however, long-term use of these agents is also associated with serious adverse events. To combat these issues and optimize therapeutic efficacy, nanotechnology-based interventions have been emerged as viable option. While, nanomedicines signposted superiority over the conventional pharmacological moieties; there are still many pharmacokinetic and pharmacodynamic challenges to nanomedicines following their intravenous or intra-articular administration. To circumvent these challenges, significant adaptations such as PEGylation, surface conjugation of targeting ligand(s), and site- responsive behavior (i.e., pH-, biochemical-, or thermal-responsiveness) have been implemented. Besides, multi-functionalization of nanomedicines has been emerging as an exceptional strategy to overcome pharmacokinetic challenges, improve targetability to inflamed synovium, maximise internalisation into the activated macrophages, and improved therapeutic outcomes for treatment of RA. Therefore, this review aims to conceptualize and recapitulate the substantial evidences regarding the pharmacokinetic and pharmacodynamic superiority of multi-functionalized nanomedicines over the naked nanomedicines for site-selective targeting to inflamed synovium and rational treatment of RA and other rheumatic co-morbidities. Pharmaceutical sustainability of the multi-functionalized nanomedicines for improved biocompatibility, profound interaction with the targeting tissue/cells/sub-cellular domain, and diminished systemic toxicity has also been pondered.
30864698 Upregulation of microRNA‑590 in rheumatoid arthritis promotes apoptosis of bone cells th 2019 May The aim of the present study was to further define the role of microRNA (miR)‑590 in osteoarthritis (OA) and to investigate the underlying mechanism. In brief, reverse transcription‑quantitative polymerase chain reaction was used to analyze miR‑590 expression in bone tissue samples from rats with OA. Results indicated the expression of miR‑590 was increased. miR‑590 upregulation induced apoptosis in bone cells, whereas miR‑590 downregulation reduced apoptosis of bone cells. Furthermore, miR‑590 upregulation suppressed the protein expression levels of transforming growth factor (TGF)‑β1, phosphoinositide 3‑kinase (PI3K) and phosphorylated (p)‑Akt in bone cells. However, downregulation of miR‑590 induced the protein expression levels of TGF‑β1, PI3K and p‑Akt in bone cells. In addition, TGF‑β1 attenuated the effects of miR‑590 upregulation on bone cell apoptosis and the inactivation of PI3K inhibited the effects of miR‑590 downregulation on bone cell apoptosis. Taken together, the present data suggested that miR‑590 promoted apoptosis in bone cells from rats with OA by regulating the TGF‑β1/PI3K signaling pathway.
31164519 [A Case of Small Bowel Perforation Caused by Malignant Lymphoma after Methotrexate Therapy 2019 Apr A 73-year-old woman had a history of medication, including methotrexate for rheumatoid arthritis, for 5 years. She had chronic epigastralgia for 2 weeks and found to have multiple submucosal tumors on upper gastrointestinal endoscopy in another hospital. She had a strong abdominal pain thereafter and diagnosed as having gastrointestinal perforation on the basis of CT scans. Abdominal examination revealed disseminated peritonitis, and emergency laparoscopic surgery was performed on the day of admission. A 1 cm perforation of the ileum was identified, and a 5 cm mass of the mesentery near the perforation was also identified. Small bowel partial resection, including both lesions, was performed. From the intraoperative findings, methotrexate-associated lymphoproliferative disorders(MTX-LPD)was suspected, and methotrexate was discontinued after the surgery. At a later date, the pathological result from both the surgical specimen and upper gastrointestinal endoscopy was diffuse large B cell lymphoma(DLBCL). CT scan, PET-CT scan, and upper gastrointestinal endoscopy were performed 1-2 months after surgery, and no tumor was identified. Currently, 6 months after the surgery, the patient is still alive without any progression of the lymphoma.
31665107 Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumato 2019 Dec 18 Background There is a need for additional biomarkers to assist in the diagnosis and prognosis of rheumatoid arthritis (RA). The aim of our study was to evaluate the (pre-analytical, analytical and clinical) performance of serum calprotectin as a marker of inflammation in RA. Methods The study population included 463 rheumatologic patients (including 111 RA patients and 352 controls) who for the first time consulted a rheumatologist, 20 healthy controls and 27 patients with an infectious disease. Calprotectin was measured (using four different assays) in serum or in serum and EDTA plasma (healthy controls and infectious disease group). For rheumatologic patients, results for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were available. Results Results for blood calprotectin were assay- and matrix-dependent, with higher values found in serum than in plasma. Serum calprotectin was higher in RA patients than in rheumatologic diseased controls and in healthy controls. Serum calprotectin was lower in RA patients than in patients with an infectious disease. Serum calprotectin was associated with disease activity (DAS score). The area under the curve (AUC) to discriminate RA from controls was 0.756 for CRP, 0.714 for ESR and 0.726-0.783 for calprotectin. Conclusions Our data document that calprotectin measurement is assay- and matrix-dependent. Serum calprotectin is associated with disease activity. Additional (prospective) studies are warranted to further evaluate the prognostic and diagnostic value of blood calprotectin measurements.
31300004 Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates 2019 Jul 12 BACKGROUND: Syndecans are heparan sulfate proteoglycans that occur in membrane-bound or soluble forms. Syndecan-3, the least well-characterised of the syndecan family, is highly expressed on synovial endothelial cells in rheumatoid arthritis patients. Here, it binds pro-inflammatory chemokines with evidence for a role in chemokine presentation and leukocyte trafficking into the joint, promoting the inflammatory response. In this study, we explored the role of soluble syndecan-3 as a binder of chemokines and as an anti-inflammatory and therapeutic molecule. METHODS: A human monocytic cell line and CD14+ PBMCs were utilised in both Boyden chamber and trans-endothelial migration assays. Soluble syndecan-3 was tested in antigen-induced and collagen-induced in vivo arthritis models in mice. ELISA and isothermal fluorescence titration assays assessed the binding affinities. Syndecan-3 expression was identified by flow cytometry and PCR, and levels of shedding by ELISA. RESULTS: Using in vitro and in vivo models, soluble syndecan-3 inhibited leukocyte migration in vitro in response to CCL7 and its administration in murine models of rheumatoid arthritis reduced histological disease severity. Using isothermal fluorescence titration, the binding affinity of soluble syndecan-3 to inflammatory chemokines CCL2, CCL7 and CXCL8 was determined, revealing little difference, with K(d)s in the low nM range. TNFα increased cell surface expression and shedding of syndecan-3 from cultured human endothelial cells. Furthermore, soluble syndecan-3 occurred naturally in the sera of patients with rheumatoid arthritis and periodontitis, and its levels correlated with syndecan-1. CONCLUSIONS: This study shows that the addition of soluble syndecan-3 may represent an alternative therapeutic approach in inflammatory disease.
31504978 Methotrexate and interstitial lung disease: controversies and questions. A narrative revie 2019 Nov 1 MTX, which is the anchor-drug for the treatment of RA, has been associated with lung injury and in particular with MTX-related pneumonitis (M-pneu). Although the frequency of M-pneu has been reported to range between 0.3 and 11.6%, more recent studies and meta-analyses have challenged that, suggesting that it is less common than previously thought. M-pneu is considered a hypersensitivity reaction usually occuring early after MTX commencement, and to be dose-independent. Furthermore, it does not seem to be truly related to the development of interstitial lung disease observed in some patients as part of the natural history of RA (RA-ILD). On the other hand, there are data suggesting that clinicians should be cautious when commencing MTX in patients with pre-existing lung disease. However, treatment should not be delayed or limited in progressive RA that could lead to RA-ILD, and MTX remains one of the central players in the treat-to-target approach. In this review, we aimed to summarize the current evidence from observational studies and clinical trials on lung disease in MTX-treated RA patients. We focus the discussion on the lack of association between M-pneu and RA-ILD.
30511928 Development and application of a PCR-HRM molecular diagnostic method of SNPs linked with T 2019 Aug 27 Background Clinical evidence indicates that genetic variations may interfere with the mechanism of drug action. Recently, it has been reported that the single nucleotide polymorphisms (SNPs) of STAT4, PTPN2, PSORS1C1 and TRAF3IP2RA genes are associated with the clinical efficacy of tumor necrosis factor (TNF) inhibitors in the treatment of rheumatoid arthritis (RA) patients. Therefore, the detection of the SNPs linked with TNF inhibitor efficacy may provide an important basis for the treatment of RA. This study intended to establish molecular diagnostic methods for genotyping the linked SNPs based on high resolution melting (HRM) curve analysis. Methods The polymerase chain reaction-HRM (PCR-HRM) curve analysis detecting systems were established by designing the primers of the four SNPs, rs7574865G>T, rs7234029A>G, rs2233945C>A and rs33980500C>T, and the performance and clinical applicability of which were evaluated by using the Sanger sequencing method and genotyping test for 208 clinical samples. Results The self-developed molecular diagnostic methods of PCR-HRM were confirmed to be able to correctly genotype the four SNPs, the sensitivity and specificity of which were 100% in this study. The repeatability and reproducibility tests showed that there is little variable in intra-assay and inter-assay (the coefficient of variation ranged from 0.01% to 0.07%). The slight changes of DNA template and primer concentrations, PCR cycle number and reaction system volume had no significant effect on the genotyping performance of the method. The PCR-HRM assays were also applied to other PCR thermocyclers with HRM function and use different saturation fluorescent dyes. Conclusions The PCR-HRM genotyping method established in this study can be applied to the routine molecular diagnosis of rs7574865, rs7234029, rs2233945 and rs33980500.
31376995 Increased hospitalization rates following heart failure diagnosis in rheumatoid arthritis 2020 Feb OBJECTIVE: To compare the frequency of and trends in hospitalizations after heart failure (HF) diagnosis in patients with and without rheumatoid arthritis (RA) during 1987-2015. METHODS: The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. RESULTS: The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalization rate after HF diagnosis was higher in RA vs non-RA (rate ratio [RR] 1.17; 95%CI 1.08-1.26). Hospitalization rates in both groups have been declining since 2005 and the difference between patients with and without RA may be decreasing after 2010. The magnitude of the increase was similar in both sexes and across all ages. Patients with RA were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF or other cardiovascular causes compared to non-RA patients. CONCLUSIONS: The hospitalization rate following HF diagnosis was higher in RA versus non-RA patients regardless of sex and age. Increased hospitalization risk in patients with RA was driven by increased rates of non-cardiovascular hospitalization.
30353563 Association of galectin-3 with markers of myocardial function, atherosclerosis, and vascul 2019 Jan BACKGROUND: Galectin-3 has emerged as a promising novel biomarker of cardiovascular fibrosis in patients with cardiovascular diseases. HYPOTHESIS: We investigated whether galectin-3 correlates with markers of vascular fibrosis, subclinical atherosclerosis, and cardiac function in patients with rheumatoid arthritis (RA), a disease accompanied by high cardiovascular risk. METHODS: RA and non-RA individuals underwent applanation tonometry, carotid ultrasound, and impedance cardiography, to obtain markers of arterial stiffness, subclinical atherosclerosis, and myocardial function, respectively. Cardiovascular risk was estimated from the Framingham Heart Study. Serum levels of galectin-3 were determined by enzyme-linked immunosorbent assay. RESULTS: Galectin-3 was elevated in RA patients (n = 85) compared to controls (n = 39), but this difference was no longer significant after adjustment for the presence of cardiovascular comorbidities. In the univariate analysis, galectin-3 significantly correlated with markers of vascular stiffness (including pulse wave velocity, central blood pressure, central and peripheral pulse pressure, and total arterial compliance); atherosclerosis (carotid intima-media thickness); myocardial blood flow (cardiac output, stroke volume) and contractibility (acceleration and velocity index); systemic vascular resistance, and estimated cardiovascular risk. Multivariate analysis models revealed an independent association between galectin-3 and both cardiac output (β = -0.274, P = 0.039), as well as systemic vascular resistance (β = 0.266, P = 0.039). CONCLUSIONS: In a relatively well-controlled cohort of RA patients with low-grade systemic inflammation and long-standing disease, serum galectin-3 might be useful as a marker of cardiac function and cardiovascular fibrosis.
31423560 Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseas 2019 Oct Interstitial lung disease (ILD) is a common manifestation of systemic autoimmune diseases and a leading cause of death in these patients. A proportion of patients with autoimmune ILDs develop a progressive fibrosing form of ILD, characterized by increasing fibrosis on high-resolution computed tomography, worsening of lung function, and early mortality. Autoimmune disease-related ILDs have a variable clinical course and not all patients will require treatment, but all patients should be monitored for signs of progression. Apart from systemic sclerosis-associated ILD, the limited evidence to support the efficacy of immunosuppression as a treatment for ILDs is based mainly on small retrospective series and expert opinion. Non-clinical data suggest that there are commonalities in the mechanisms that drive progressive fibrosis in ILDs with an immunological trigger as in other forms of progressive fibrosing ILD. This suggests that nintedanib and pirfenidone, drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis, may also slow the progression of ILD associated with systemic autoimmune diseases. In the SENSCIS® trial, nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD. The results of other large clinical trials will provide further insights into the role of anti-fibrotic therapies in the treatment of autoimmune disease-related ILDs.
31730022 Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumato 2019 Nov 15 BACKGROUND: Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool for identifying disease biomarkers. The aim of this study was to compare the metabolic blueprint of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) derived from RA and OA patients. METHODS: Somatic cells of RA patients (n = 3) and OA patients (n = 3) were isolated, transduced with a lentiviral plasmid, and reprogrammed into iPSCs displaying pluripotency. Metabolic profiling of RA and OA patient-derived FLS cells and iPSCs was performed using liquid chromatography/mass spectrometry and statistical analysis. After normalization by the sum of the peak intensities through LC/MS, 37 metabolites were detected across RA and OA patients. RESULTS: The metabolites of RA and OA were distinguishable according to the PLS-DA analysis. LysoPC (20:4), 4-methoxychalcone, phosphorylcholine, and nicotinamide (NAM) were significantly higher in RA iPSCs than in OA iPSCs (p < 0.05). The NMNAT-3 enzyme, which catalyzes an important step in the biosynthesis of NAD(+) from adenosine triphosphate, was also upregulated in RA iPSCs. Interestingly, the proliferation of RA iPSCs was significantly greater than OA iPSC proliferation (p < 0.05). NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. When iPSCs were treated with 100 nM of the NAM inhibitor tannic acid (TA), the proliferation of RA iPSCs was significantly reduced (p < 0.001). CONCLUSIONS: The metabolites of RA and OA FLS cells and RA and OA iPSCs were all clearly distinguishable from each other. NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. TA effectively inhibited the expression of NAM in RA iPSCs and is a possible effective treatment for RA patients.
31614911 Proinflammatory Effects of IL-1β Combined with IL-17A Promoted Cartilage Degradation and 2019 Oct 13 Combinations of IL-1β and other proinflammatory cytokines reportedly promote the severity of arthritis. We aimed to investigate the effects of IL-1β combined with IL-17A on cartilage degradation and synthesis in in vitro models. Cartilage explant degradation was determined using sulfated glycosaminoglycans (S-GAGs) levels, matrix metalloproteinase (MMP13) gene expression, uronic acid, and collagen contents. Cell morphology and accumulation of proteoglycans were evaluated using hematoxylin-eosin and safranin O staining, respectively. In the pellet culture model, expressions of cartilage-specific anabolic and catabolic genes were evaluated using real-time qRT-PCR. Early induction of MMP13 gene expression was found concomitantly with significant S-GAGs release. During the prolonged period, S-GAGs release was significantly elevated, while MMP-13 enzyme levels were persistently increased together with the reduction of the cartilaginous matrix molecules. The pellet culture showed anabolic gene downregulation, while expression of the proinflammatory cytokines, mediators, and MMP13 genes were elevated. After cytokine removal, these effects were restored to nearly basal levels. This study provides evidence that IL-1β combined with IL-17A promoted chronic inflammatory arthritis by activating the catabolic processes accompanied with the suppression of cartilage anabolism. These suggest that further applications, which suppress inflammatory enhancers, especially IL-17A, should be considered as a target for arthritis research and therapy.
31168411 Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a random 2019 OBJECTIVES: Glucocorticoids have anti-inflammatory, transrepression-mediated effects, although adverse events (AEs; transactivation-mediated effects) limit long-term use in patients with rheumatoid arthritis (RA). We evaluated the efficacy and safety of fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, versus prednisone or placebo. METHODS: In this 12-week, phase II, randomised controlled trial, 323 patients with moderate to severe RA were randomised 1:1:1:1:1:1:1 to fosdagrocorat (1 mg, 5 mg, 10 mg or 15 mg), prednisone (5 mg or 10 mg) or placebo, once daily. The primary endpoints (week 8) were American College of Rheumatology 20% improvement criteria (ACR20) responses, and percentage changes from baseline in biomarkers of bone formation (procollagen type 1 N-terminal peptide [P1NP]) and resorption (urinary N-telopeptide to urinary creatinine ratio [uNTx:uCr]). Safety was assessed. RESULTS: ACR20 responses with fosdagrocorat 10 mg and 15 mg were superior to placebo, and fosdagrocorat 15 mg was non-inferior to prednisone 10 mg (week 8 model-predicted ACR20 responses: 47%, 61%, 69% and 73% vs 51%, 71% and 37% with fosdagrocorat 1 mg, 5 mg, 10 mg and 15 mg vs prednisone 5 mg, 10 mg and placebo, respectively). Percentage changes from baseline in P1NP with fosdagrocorat 1 mg, 5 mg and 10 mg met non-inferiority criteria to prednisone 5 mg. Corresponding changes in uNTx:uCr varied considerably. All fosdagrocorat doses reduced glycosylated haemoglobin levels. AEs were similar between groups; 63 (19.5%) patients reported treatment-related AEs; 9 (2.8%) patients reported serious AEs. No patients had adrenal insufficiency, treatment-related significant infections or laboratory abnormalities. No deaths were reported. CONCLUSION: In patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg. TRIAL REGISTRATION NUMBER: NCT01393639.
30877214 Evaluation of the Implementation of Guidelines on the Treatment of Osteoporosis in Patient 2020 Jan OBJECTIVE: To assess whether the 2003 and 2014 French guidelines on the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) and the 2012 update of the French guidelines for the treatment of postmenopausal osteoporosis (PMOP) were applied in patients with rheumatoid arthritis (RA). METHODS: We conducted a cross-sectional study of 776 patients with RA (19 centers). We collected the data required for the application of the various recommendations (age, sex, prednisone intake, low-energy fracture, history in the immediate family of hip fractures, and bone densitometry), anti-osteoporotic drugs, and the various factors that may be associated with the application of the recommendations. RESULTS: Of the patients who should have received antiosteoporosis treatment, there were 22.6% actually treated (according to the 2014 guidelines), 27.3% actually treated according to the 2003 guidelines, and of postmenopausal women, 23.6% (according to the 2012 PMOP guidelines). Applying the 2014 GIOP guidelines increased the theoretical number of patients requiring treatment relative to the 2003 GIOP guidelines (77% vs 53%; p < 0.001). In multivariate analysis, being treated was associated with a spinal T score ≤ -2 SD according to the 2014 guidelines; with not taking part in physical activity for more than 30 min a day according to the 2003 guidelines; and with older age, lower body mass index, and a T score ≤ -2.5 SD in at least 1 site according to the PMOP guidelines. CONCLUSION: Patients with RA had inadequate prevention of GIOP and PMOP. The management of osteoporosis needs to be improved in this population.
30871593 Impact of synthetic and biological immunomodulatory therapy on the duration of 17DD yellow 2019 Mar 14 BACKGROUND: The 17DD-yellow fever (YF) vaccine induces a long-lasting protective immunity, resulting from humoral and cellular immunological memory. The treatment of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARD) may affect pre-existing 17DD-vaccine protective immunity and increase the risk of acquiring YF infection. Our goal was to determine whether DMARD would affect the duration of YF-specific protective immunity in RA patients. METHODS: A total of 122 RA patients, previously immunized with the 17DD-YF vaccine (1-5, 5-9, and ≥ 10 years) and currently under DMARD therapy, were enrolled in the present investigation. Immunomodulatory therapy encompasses the use of conventional synthetic DMARD alone (csDMARD) or combines with biological DMARD (cs+bDMARD). A total of 226 healthy subjects were recruited as a control group (CONT). Neutralizing antibody responses were measured by a plaque-reduction neutralization test (PRNT), and cellular immunity was evaluated by an in vitro 17DD-YF-specific peripheral blood lymphoproliferative assay. RESULTS: The data demonstrated that csDMARD therapy did not affect the duration of protective immunity induced by the 17DD-YF vaccine compared to that of CONT, as both presented a significant time-dependent decline at 10 years after vaccination. Conversely, cs+bDMARD therapy induced a premature depletion in the main determinants of the vaccine protective response, with diminished PRNT seropositivity levels between 5 and 9 years and impaired effector memory in CD8(+) T cells as early as 1-5 years after 17DD-YF vaccination. CONCLUSIONS: These findings could support changing the vaccination schedule of this population, with the possibility of a planned booster dose upon the suspension of bDMARD in cases where this is allowed, even before 10 years following 17DD-YF vaccination. The benefit of a planned booster dose should be evaluated in further studies. TRIAL REGISTRATION: RBR-946bv5 . Date of registration: March 05, 2018. Retrospectively registered.
31280937 Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional 2020 Feb OBJECTIVES: To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). METHODS: Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan-Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. RESULTS: 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. CONCLUSION: In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.
31054771 Trends in Prevalence of Functional Disability in Rheumatoid Arthritis Compared With the Ge 2019 Jun The objective of the study was to assess trends in functional disability (FD) in patients with rheumatoid arthritis (RA) vs individuals without RA. This retrospective population-based study included 586 patients with RA and 531 individuals without RA. Information on activities of daily living was obtained from self-report questionnaires. The prevalence of FD was higher in those with RA (586 [26%]) vs those without RA (531 [11%]) at RA incidence/index date (P<.001), with persistent excess over the follow-up and calendar time. Patients with RA had a 15% or higher prevalence of FD than individuals without RA in most age groups. Patients with RA have a higher prevalence of FD across RA duration, age, and calendar time than those without RA.
30679233 Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumato 2019 Jan 24 OBJECTIVE: To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis. DESIGN: Population based prospective study. SETTING: 53 university and 54 non-university clinical centres in France. PARTICIPANTS: 3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months. INTERVENTION: Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis. MAIN OUTCOME MEASURE: The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LED(wf)), which measures the difference between average duration of survival without failure. RESULTS: Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LED(wf) 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events. CONCLUSION: Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.
31273493 When can I go home after my knee replacement? Factors affecting the duration of in-hospita 2019 Dec BACKGROUND: Despite a sevenfold decline in the number of postoperative nights (21-3) after a total knee arthroplasty (TKA) over the last four decades, predictors of length of stay (LOS) are not fully understood. We attempted to ascertain these factors by analyzing a large cohort of patients. METHODS: Prospectively collected data between January 2016 and March 2017 were retrospectively analyzed at our institute. Charts of 1663 consecutive, simple primary unilateral and bilateral TKAs were reviewed for the LOS excluding staggered bilateral, complex primary and revision knees. STATISTICAL ANALYSIS: Preoperative variables [demographics, cash/credit status, historical, clinical, laboratory findings, Knee Society Function Scores and Oxford Knee Scores (OKSs)] were scrutinized by multivariate regression to identify significant factors affecting LOS and formulate model equations for patients and health caregivers. Results were incorporated into an iOS application, which was tested for accuracy. RESULTS: Among 1524 unilateral and 139 bilateral TKAs, mean LOS was 4.4 and 5.2 days, respectively. Five factors, namely insurance, flexion/hyperextension deformity, preoperative OKS and a rheumatoid etiology, were significantly associated with prolonged LOS in unilateral knees. The impact of these independent variables on LOS could be calculated by: [Formula: see text]For bilateral cases, the only significant variable extending LOS was a low preoperative OKS and the equation is given as follows: [Formula: see text]The iOS-app-predicted LOS and actual LOS were similar (p > 0.05) for 115 prospectively operated knees. CONCLUSION: Poor preoperative OKS, rheumatoid etiology, flexion and hyperextension deformity and delays in insurance affected unilateral TKR LOS, while poor preoperative OKS alone affected LOS in bilateral cases.