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ID PMID Title PublicationDate abstract
30252968 Interactions between rheumatoid arthritis synovial fibroblast migration and endothelial ce 2019 Feb Leukocytes travel within the circulation and enter connective tissues by interactions with endothelium of postcapillary venules mediated by cell adhesion molecules, summarized as the leukocyte adhesion cascade. In the severe combined immunodeficient (SCID) mouse model, rheumatoid arthritis (RA) synovial fibroblasts (SF) migrated to distant cartilage through the vasculature. Therefore, RASF adhesion toward endothelial cells (EC) and E- and P-selectins were analyzed. Cell-to-cell binding assays between SF and EC were performed. Interactions of SF with tumor necrosis factor α (TNFα)-activated EC or selectins were analyzed in flow adhesion assays. Immunohistochemistry for E-selectin ligand CD15s was performed. CD15s induction in RASF by human serum or media was evaluated. Wild-type and E(-/-/) P(-/-) Selectin-SCID mice were used for inverse-wrap surgery. After laser-mediated microdissection, real-time PCR for E-/P-selectin/vascular cell adhesion molecule 1 was performed. Adhesion between SF/EC under static conditions was highest in Roswell Park Memorial Institute-cultured RASF to TNFαα-activated human umbilical vein endothelial cells (2.25-fold) and RASF adhesion was higher toward venous than arterial EC (Dulbecco's modified eagle medium P = 0.0419, RPMI P = 0.0119). In flow chamber assays, RASF adhesion to E-selectin was higher than to P-selectin (e.g. 0.9 dyn cm(-2) P = 0.0001). Osteoarthritis synovial fibroblasts showed lower rolling/adhesion properties (e.g. 0.5 dyn cm(-2) , P = 0.0010). RASF adhesion to TNFαα-activated EC was increased (e.g. 0.9 dyn cm(-2) , P = 0.0061). CD15s induction in RASF was strongest in RA serum. Vimentin/CD15s double-positive cells were detectable. In E-/P-selectin-deficient mice, contralateral invasion was reduced (P = 0.023). E- and P-selectin, and vascular cell adhesion molecule 1 expression in EC of implants was confirmed. Our data indicate that the milieu within vessels induces CD15s which enables RASF to interact with E-selectin/EC under flow. Therefore, RASF may migrate to distant sites and leave the vasculature similarly to leukocytes.
30570833 Risk of Hospitalized Infection and Initiation of Abatacept Versus Tumor Necrosis Factor In 2020 Jan OBJECTIVE: We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS: Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS: We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION: In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
31221815 MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast- 2019 Jul 31 Behavior alterations in fibroblast-like synoviocytes (FLS) contribute to a pivotal role in pathogenesis of rheumatoid arthritis (RA). MiRNAs are closely involved in a variety of pathologic conditions. In the present study, we aimed to screen for the aberrant expression of miRNAs in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to further identify the altered expression of miR-26a-5p in RA-FLS and to investigate the role of miR-26a-5p in RA. The altered expression of miR-26a-5p in RA-FLS was screened by microarray analysis and confirmed by quantitative real time PCR. The effect of miR-26a-5p on proliferation, cell cycle, apoptosis, and invasion in RA-FLS were studied. The verification of miR-26a-5p target mRNA and downstream signaling pathway was elucidated by bioinformatics analysis, dual luciferase reporter assay, and western blot. Expression of miR-26a-5p was higher in RA-FLS than in fibroblast-like synoviocytes from osteoarthritis patients and trauma patients. Overexpression of miR-26a-5p RA-FLS promoted cells proliferation, G1/S transition, cells invasion, and resisted apoptosis in RA-FLS, whereas it led to contrary effects when inhibiting the expression of miR-26a-5p. The 3'UTR of tensin homolog (PTEN) was directly targetted by miR-26a-5p and activation of phosphoinositide 3-kinase (PI3K)/AKT pathway was observed when overexpression of miR-26a-5p. Our study suggested that miR-26a-5p has a complementary role in cells proliferation, invasion, and apoptosis of RA-FLS, which may be attributed to its activation effect on PI3K/AKT signaling pathway via targetting PTEN. MiR-26a-5p is likely to be a clinically helpful target for novel therapeutic strategies in RA.
30802622 Latent tuberculosis infection and non-infectious co-morbidities: Diabetes mellitus type 2, 2019 Mar The prevalence of non-communicable diseases is increasing worldwide, which coincides with the persistence of infectious diseases including tuberculosis. These can synergistically affect individual and population health. Three non-communicable diseases that are relevant because of their associated morbidity, mortality and disability are type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis. There is some evidence that patients with these conditions are at increased risk of acquiring latent tuberculosis infection (LTBI) and of this progressing to active disease. Unfortunately, evidence on accurate testing and effective prophylactic treatment in these populations is lacking. This review discusses current evidence and recommendations for management of LTBI in these patients.
31091104 Evaluation of Targeting Efficiency of Joints with Anticollagen II Antibodies. 2019 Jun 3 Diseases of the joints affect over 10% of the world's population, resulting in significant morbidity. There is an unmet need in strategies for specific delivery of therapeutics to the joints. Collagen type II is synthesized by chondrocytes and is mainly restricted to the cartilage and tendons. Arthrogen-CIA is a commercially available anticollagen II antibody cocktail that reacts with 5 different epitopes on human, bovine, and mouse collagen II. Arthrogen has been used for induction of experimental rheumatoid arthritis (RA) in mice because of high complement activation on the cartilage surface. Native collagen II might serve as a useful target for potential delivery of therapeutics to the joint. To evaluate the efficiency and specificity of targeting collagen II, Arthrogen was labeled with near-infrared (NIR) dye IRDye 800 or IRDye 680. Using ex vivo NIR imaging, we demonstrate that Arthrogen efficiently and specifically accumulated in the limb joints regardless of the label dye or injection route (intravenous and subcutaneous). After subcutaneous injection, the mean fluorescence of the hind limb joints was 19 times higher than that of the heart, 8.7 times higher than that of the liver, and 3.7 times higher than that of the kidney. Control mouse IgG did not show appreciable accumulation. Microscopically, the antibody accumulated on the cartilage surface of joints and on endosteal surfaces. A monoclonal antibody against a single epitope of collagen II showed similar binding affinity and elimination half-life, but about three times lower targeting efficiency than Arthrogen in vitro and ex vivo, and about two times lower targeting efficiency in vivo. We suggest that an antibody against multiple epitopes of collagen II could be developed into a highly effective and specific targeting strategy for diseases of the joints or spine.
30286609 The prevalence of depression and insomnia symptoms among patients with rheumatoid arthriti 2019 Mar The objective of the study was to assess the prevalence of symptoms of depression and insomnia among patients with rheumatoid arthritis and osteoarthritis in comparison with individuals without chronic diseases. The study was carried out at National Institute of Geriatrics, Rheumatology and Rehabilitation, included 229 persons. The participants were divided into the following groups: group I - 120 patients with rheumatoid arthritis, group II - 58 patients with osteoarthritis, group III - 51 healthy individuals no confirmed depression (control group). Symptoms of depression were confirmed by a multiple-choice self-reported Beck Depression Inventory questionnaire. Symptoms of depression confirmed with depression inventory≥ 10 occurred as follows: patients with rheumatoid arthritis - 75.83%, patients with osteoarthritis - 50%, control group - 23.53% (p<0.0001), with the prevalence of insomnia (AIS≥6) at: 71%, 32% and 33%, respectively (p<0.001). In group I mean values of FIRST and AIS were 23.06 and 8.36 respectively, with group II: 21.71 and 7.84, respectively. In all subjects with AIS≥6, the depression inventory was statistically significantly (p<0.005) higher than in the subjects with AIS<6 (respectively: 17.02 vs 12.13; 15.6 vs 8.05; 5.45 vs 1.81). Patients with rheumatoid arthritis find it difficult to cope with stress. Insomnia as a reaction to stress occurs more often in this group.
31853733 Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid 2020 Mar INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients. METHODS: We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016. RESULTS: We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi). CONCLUSIONS: The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed. Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting. Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019. Key Points • One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution. • Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.
31865241 ASIC1a promotes synovial invasion of rheumatoid arthritis via Ca(2+)/Rac1 pathway. 2020 Feb Acid-sensitive ion channels (ASICs) as Ca(2+) and Na(+) cation channels are activated by changing in extracellular pH, which expressed in various diseases and participated in underlying pathogenesis. ASIC1a is involved in migration and invasion of various tumor cells. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) located at the edge of the synovium were identified as key players in the pathophysiological process of rheumatoid arthritis and reported to have many similar properties to tumor cells. Here, we investigated the roles of ASIC1a in synovial invasion in vivo and the migration and invasion of RA-FLSs in vitro. Our results showed ASIC1a highly expressed in RA synovial tissues and RA-FLSs. Inhibition of ASIC1a by PCTX-1 reduces synovial invasion and the expressions of MMP2, MMP9, p-FAK to protect articular cartilage in AA rats. Moreover, the acidity-promoted invasion and migration as well as the expressions of MMP2, MMP9, p-FAK of RA-FLSs were down-regulated by ASIC1a-RNAi and PCTX-1 while they were increased by overexpression-ASIC1a. ASIC1a mediated Ca(2+) influx and the activation of Ras-related C3 botulinum toxin substrate 1(Rac1), which was decreased by the intracellular calcium chelating agent BAPTA-AM. Meanwhile, the migration and invasion as well as the expressions of MMP2, MMP9, p-FAK of RA-FLSs were decreased by Rac1 specific blocker NSC23766. In conclusion, this study indicated that ASIC1a may be a master regulator of synovial invasion via Ca(2+)/Rac1 pathway.
29718746 Japan College of Rheumatology guideline for the use of methotrexate in patients with rheum 2019 Jan Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for treatment of RA in Japan in 1999 at the recommended dose of 6-8 mg/week; it was approved as first-line drug with the maximum dose of 16 mg/week in February 2011. However, more than half of Japanese patients with RA are unable to tolerate a dose of 16 mg/week of MTX. Moreover, some serious adverse events during the treatment with MTX, such as pneumocystis pneumonia (PCP) and lymphoproliferative disorders (LPD) have been observed much more frequently in Japan than in other countries. Therefore, this article, an abridged English translation summarizing the 2016 update of the Japan College of Rheumatology (JCR) guideline for the use of MTX in Japanese patients with RA, is not intended to be valid for global use; however, it is helpful for the Japanese community of rheumatology and its understanding might be useful to the global community of rheumatology.
31236568 Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rhe 2019 Dec 1 OBJECTIVES: To investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response. METHODS: The Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed. RESULTS: In the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU. CONCLUSION: All regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients' prognosis. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639.
30593416 Pleiotropic functions of plasmacytoid dendritic cells in the pathogenesis of the rheumatoi 2019 Jan Rheumatoid arthritis is a chronic autoimmune inflammatory disease with an unclear etiology. The disease is characterized by infiltration of synovial tissue with immune cells, among which there are dendritic cells that play multifaceted roles in the pathogenesis of the disease. Here we shall assume that plasmacytoid dendritic cells are able to change their phenotype under the influence of various stimuli, thereby modulating the course of the disease, contributing to both the development of exacerbations and the induction of remissions depending on the phenotype they have acquired. This property can be used to develop new methods of immunotherapy.
31253980 A genetics-led approach defines the drug target landscape of 30 immune-related traits. 2019 Jul Most candidate drugs currently fail later-stage clinical trials, largely due to poor prediction of efficacy on early target selection(1). Drug targets with genetic support are more likely to be therapeutically valid(2,3), but the translational use of genome-scale data such as from genome-wide association studies for drug target discovery in complex diseases remains challenging(4-6). Here, we show that integration of functional genomic and immune-related annotations, together with knowledge of network connectivity, maximizes the informativeness of genetics for target validation, defining the target prioritization landscape for 30 immune traits at the gene and pathway level. We demonstrate how our genetics-led drug target prioritization approach (the priority index) successfully identifies current therapeutics, predicts activity in high-throughput cellular screens (including L1000, CRISPR, mutagenesis and patient-derived cell assays), enables prioritization of under-explored targets and allows for determination of target-level trait relationships. The priority index is an open-access, scalable system accelerating early-stage drug target selection for immune-mediated disease.
30796902 Anti-oxidant and anti-inflammatory effects of cinnamaldehyde and eugenol on mononuclear ce 2019 Jun 5 Rheumatoid arthritis (RA) is an autoimmune disorder affecting joints and frequently characterized by initial local and later systemic inflammation. The present study was conducted with the aim to determine the anti-inflammatory and antioxidant effects of cinnamaldehyde and eugenol in the peripheral blood mononuclear cells (PBMC) of RA patients. PBMCs obtained from RA patients were treated with varying concentrations of cinnamaldehyde and eugenol. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were monitored in the 24-h culture supernatant of PBMCs. Reactive oxygen species formation, biomolecular oxidation and the activities of antioxidant enzymes were also determined. FTIR analysis was done to determine structural alterations in the PBMCs. Molecular docking was performed to gain an insight into the binding mechanism of eugenol and cinnamaldehyde with pro-inflammatory cytokines. The levels of pro-inflammatory cytokines and markers of oxidative stress were found to be elevated in the PBMC culture of RA patients as compared to the healthy controls. Cinnamaldehyde and eugenol have significantly reduced the levels of cytokines. Reactive oxygen species formation, biomolecular oxidation and antioxidant defense response were also ameliorated by treating PBMCs with both the compounds. FTIR results further confirms cinnamaldehyde and eugenol mediated protection to biomolecules of PBMCs of RA patients. Molecular docking results indicates interaction of cinnamaldehyde and eugenol with key residues of TNF-α and IL-6. Cinnamaldehyde and eugenol were found to exert potent anti-inflammatory and anti-oxidant effects on the PBMC culture of RA patients. So, these compounds may be used as an adjunct in the management of RA.
29807445 Predictive factors for structural remission using abatacept: Results from the ABROAD study 2019 May OBJECTIVE: To investigate the effect of abatacept (ABA) on preventing joint destruction in biological disease-modifying anti-rheumatic drug (bDMARD)-naïve rheumatoid arthritis (RA) patients in real-world clinical practice. PATIENTS AND METHODS: RA patients were collected from the ABROAD (ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD) study cohort. They had moderate or high disease activity and were treated with ABA as a first-line bDMARD. Radiographic change between baseline and 1 year after ABA treatment was assessed with the van der Heijde's modified Total Sharp Score (mTSS). Predictive factors for structural remission (St-REM), defined as ΔmTSS ≤0.5/year, were determined. RESULTS: Among 118 patients, 81 (67.5%) achieved St-REM. Disease duration <3 years (odds ratio (OR) = 3.152, p = .007) and slower radiographic progression (shown as 'baseline mTSS/year <3', OR = 3.727, p = .004) were independently significant baseline predictive factors for St-REM irrespective of age and sex. St-REM prevalence increased significantly if clinical remission based on the Simplified Disease Activity Index was achieved at least once until 24 weeks after ABA treatment. CONCLUSION: Shorter disease duration, smaller radiographic progression at baseline, and rapid clinical response were predictive factors for sustained St-REM after ABA therapy in bDMARD-naïve RA patients.
30770544 Immune cell metabolism in autoimmunity. 2019 Aug Immune metabolism is a rapidly moving field. While most of the research has been conducted to define the metabolism of healthy immune cells in the mouse, it is recognized that the overactive immune system that drives autoimmune diseases presents metabolic abnormalities that provide therapeutic opportunities, as well as a means to understand the fundamental mechanisms of autoimmune activation more clearly. Here, we review recent publications that have reported how the major metabolic pathways are affected in autoimmune diseases, with a focus on rheumatic diseases.
30634866 Time to update the ICF by including socioemotional qualities of participation? The develop 2020 May Purpose: The aim of was to identify and illustrate in what situations and with what qualities people with early RA experience participation in every day's life.Methods: Fifty-nine patients (age 18-63 years) were interviewed; 25 men and 34 women. Content analysis was used to identify meaning units that were sorted based on the type of situations described and later on, categories based on quality aspects of participation were developed.Results: Participation was described as: 1. being part of a group, where a sense of belonging arose. 2. In doing activities with others for example at work or in leisure. 3. When sharing everyday chores and responsibilities for example in domestic duties. 4. When experiencing influence on actions such as when being asked for opinions on how to conduct a specific task. 5. When having the possibility to give direction of goals in rehabilitation, or elsewhere. 6. When sharing decision making and experiencing a high degree of influence in the situation.Conclusions: Participation from an individual's perspective is about belonging and having influence that mediates a positive feeling of being included and that you matter as a person. The results are important when using participation as a goal in clinical care. It is important to expand participation beyond the definitions in ICF and guidelines to include the patients' socio-emotional participation in order to promote health.Implications for rehabilitationFacilitation of participation in daily activities is an important part of rehabilitation.Participation is expressed as determined by a person's unique life circumstances often in engagement with others.It is important to expand participation beyond the definitions in ICF and guidelines to include the patients' socio-emotional participation in order to promote health.Collected information about socioemotional participation can serve as a starting point for interventions aimed at the patient's social environment and also provide support for health professions how to involve significant others in the rehabilitation.
30745815 Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rh 2019 The Angiopoietin-2 (Ang2) gene encodes angiogenic factor, and the polymorphisms of Ang2 gene predict risk of various human diseases. We want to investigate whether the single nucleotide polymorphisms (SNPs) of the Ang2 gene can predict the risk of rheumatoid arthritis (RA). Between 2016 and 2018, we recruited 335 RA patients and 700 control participants. Comparative genotyping for SNPs rs2442598, rs734701, rs1823375 and rs12674822 was performed. We found that when compared with the subjects with the A/A genotype of SNP rs2442598, the subjects with the T/T genotype were 1.78 times likely to develop RA. The subjects with C/C genotype of SNP rs734701 were 0.53 times likely to develop RA than the subjects with TT genotype, suggesting the protective effect. The subjects with G/G genotype of SNP rs1823375 were 1.77 times likely to develop RA than the subjects with C/C genotype. The subjects with A/C and C/C genotype of SNP rs11137037 were 1.65 and 2.04 times likely to develop RA than the subjects with A/A genotype. The subjects with G/T and T/T genotype of SNP rs12674822 were 2.42 and 2.25 times likely to develop RA than the subjects with G/G genotype. The T allele over rs734701 can lead to higher serum erythrocyte sedimentation rate level (p = 0.006). The A allele over rs11137037 was associated with longer duration between disease onset and blood sampling (p = 0.003). Our study suggested that Ang2 might be a diagnostic marker and therapeutic target for RA therapy. Therapeutic agents that directly or indirectly modulate the activity of Ang2 may be the promising modalities for RA treatment.
31297605 [Treatment algorithm for rheumatoid arthritis : According to the S2e guidelines 2018]. 2019 Aug Every patient suffering from active rheumatoid arthritis should be treated with disease-modifying antirheumatic drugs (DMARD) but methotrexate initially remains the first choice treatment. Treatment should comply with the treat-to-target principle. The therapeutic aim is remission if attainable or at least a low disease activity. Remission is defined as a simplified disease activity score index (SDAI) of ≤3.3 or as fulfilling the so-called Boolean criteria. A first evaluation of the response is due after 12 weeks. At this time there should be a measurable response defined as an improvement of at least 50% of the composite score, e.g. the DAS28. If no improvement has been achieved, treatment should be continued with either a second DMARD strategy conventionally with synthetic DMARDs (csDMARDs) or an alternative with biological (bDMARD) or targeted synthetic (tsDMARDs) DMARD, depending on whether there are risk factors for a severe disease progression. A change within bDMARDs and tsDMARDs as well as therapeutic de-escalation are both possible measures in the further course of treatment.
31439227 Optimization of ultrasonographic examination for the diagnosis of erosive Rheumatoid Arthr 2019 Sep OBJECTIVE: to determine thresholds and better scenario for the diagnosis of erosive rheumatoid arthritis (RA) by ultrasonography (US) in RA in comparison to osteoarthritic (OA) patients. METHODS: Patients, prospectively included, fulfilling ACR 1987; ACR/EULAR 2010 criteria for RA or hand OA criteria. Radiographic assessment (RX): Sharp erosion score, evaluated by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). Definition of eroded RX RA: EULAR 2013 Definition. In US, erosions were scored on six bilateral joints (MCP2-3, 5; MTP2-3, 5) with a four-grade scale. RESULTS: A total of 168 patients were included: 122 RA (32 early RA < 2 years; 90 late RA ≥ 2 years); 46 OA patients. On RX: 42 RA patients (6 early; 36 late) and 5 OA patients have erosive diseases (sensitivity: 34.4%, specificity: 89.1%). On US, 95 RA patients (21 early; 78 late) and 12 OA patients have erosive diseases. Considering at least two joint facets eroded (threshold 1) or at least one joint facet eroded at grade 2 (threshold 2), sensitivities were good (68 and 72.1%), specificities excellent (89.1 and 100%). With only six targeted joint facets examined (6/30), sensitivities and specificities remained good (59.8 and 60.0%) and excellent (95.6 and 100%) with threshold 1 and 2 respectively. For all scenarios, agreement between RX and US for erosive RA was excellent ranged from 88.1% to 92.8%. CONCLUSION: US erosion assessment of six targeted joint facets detected 1.7 times more erosive RA patients than RX in late and early RA with good sensitivity and excellent specificity.
31639034 Very early MRI responses to therapy as a predictor of later radiographic progression in ea 2019 Oct 21 BACKGROUND: The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). METHODS: This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. RESULTS: Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p <  0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p <  0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p <  0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p <  0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression. CONCLUSIONS: MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01164579 .