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

ID PMID Title PublicationDate abstract
30032191 Dual inhibition of tumour necrosis factor and interleukin-17A with ABT-122: open-label lon 2018 Nov 1 OBJECTIVES: To evaluate the safety and maintenance of efficacy with ABT-122, a bi-specific monoclonal antibody targeting TNF and IL-17A, in patients with RA or PsA in open-label, 24-week extensions [open-label extensions (OLEs)] of 12-week, randomized, double-blind studies. METHODS: All patients received ABT-122 (RA, 120 mg; PsA, 240 mg) subcutaneously every other week on background MTX. Safety assessments included adverse events (AEs) and laboratory parameters. Efficacy was evaluated with ACR responses, 28-joint DAS using high-sensitivity CRP [DAS28 (hsCRP)], and Psoriasis Area and Severity Index (PsA study). RESULTS: The RA OLE study enrolled 158 patients; the PsA OLE study enrolled 168 patients. In the RA OLE study, the incidence of treatment emergent AEs (TEAEs; 41%) appeared similar to the double-blind study (36-43%). In the PsA OLE study, 57% of patients reported ⩾1 TEAE (double-blind study, 42-53%). Most TEAEs were mild or moderate in severity. There were no neutrophil abnormalities greater than grade 2. Grade 3 and/or 4 laboratory abnormalities were reported for lymphocytes, alanine aminotransferase, aspartate aminotransferase, bilirubin and haemoglobin; the number of these severe laboratory values was low (0.6-3.0%), except grade 3 lymphocyte count decreased (11.5%) in the RA study. In both OLE studies, efficacy assessed by ACR responses and other disease activity scores was maintained over the 24 weeks. CONCLUSION: ABT-122 demonstrated acceptable tolerability and maintenance of efficacy for up to 36 weeks in patients with RA or PsA receiving background MTX. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02433340 and NCT02429895.
29643425 A novel two-score system for interferon status segregates autoimmune diseases and correlat 2018 Apr 11 Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p < 0.001), while IFN-Score-B differentiated SLE and RA from HC (both p < 0.001). In SLE, both scores were associated with cutaneous and hematological (all p < 0.05) but not musculoskeletal disease activity. Comparing with bimodal (IFN-high/low) classification, significant differences in IFN-scores were found between diagnostic groups within the IFN-high group. Our continuous 2-score system is more clinically relevant than a simple bimodal classification of IFN status. This system should allow improvement in diagnosis, stratification, and therapy in IFN-mediated autoimmunity.
28256202 Intralymphatic Histiocytosis: A Report of 2 Cases. 2018 Jan Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques (sometimes forming a reticular pattern) as well as the presence of nodules and vesicles. Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area, prior surgery, or systemic disease, particularly rheumatoid arthritis. We report on 2 new cases, both associated with joint surgery in the affected area and osteoarticular disease (primary synovial osteochondromatosis and rheumatoid arthritis). This is a chronic disease and there is no specific treatment. Different treatment options were chosen in the 2 cases described. A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients.
30597393 Rheumatoid meningitis sine arthritis. 2019 Mar 15 Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even after 1 year of follow up. Clinicians should be aware of the possibility of rheumatoid meningitis without rheumatoid arthritis and keep it on the differential for patients with aseptic meningitis and otherwise negative work up.
30157931 Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T 2018 Aug 29 BACKGROUND: Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear. METHODS: In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed. RESULTS: Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression. CONCLUSIONS: Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.
29785401 Rheumatoid Arthritis and miRNAs: A Critical Review through a Functional View. 2018 Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction associated with an inflammatory environment. The etiology behind RA remains to be elucidated; most updated concepts include the participation of environmental, proteomic, epigenetic, and genetic factors. Epigenetic is considered the missing link to explain genetic diversification among RA patients. Within epigenetic factors participating in RA, miRNAs are defined as small noncoding molecules with a length of approximately 22 nucleotides, capable of gene expression modulation, either negatively through inhibition of translation and degradation of the mRNA or positively through increasing the translation rate. Over the last decade and due to the feasibility of the identification of miRNAs among different tissues and compartments, they have been proposed as biomarkers for diagnosis, prognosis, and response to treatment in different pathologies. Nevertheless, miRNAs seem to be important regulators of networks instead of single genes; their hypothetical use as biomarkers needs to rely on a functional integrative description of their effects in the biological process of autoimmune conditions which until now is missing. Therefore, we underwent a bibliographic search for review and original articles related to miRNAs and their possible implications in rheumatoid arthritis. We found 48 different studies using the key words "miRNAs" or "micro-RNAs" and "rheumatoid arthritis" with restriction of publication dates from 2011 to 2016, in humans, using the English language. After a critical reading, we provide in this paper a functional view with respect to miRNA biogenesis, interaction with targets that are expressed in specific cells and tissues, during different stages of inflammatory responses associated with RA, and recognized specific areas where miRNAs might also have a pathogenic role but remain undescribed. Our results will be useful in designing future research projects that can support miRNAs as biomarkers or therapeutic targets in RA.
29142029 Routine Use of Quantitative Disease Activity Measurements among US Rheumatologists: Implic 2018 Jan OBJECTIVE: The aim of our study was to examine why real-world practices and attitudes regarding quantitative measurements of rheumatoid arthritis (RA) have received limited attention. METHODS: An e-mail survey asked US rheumatologists to self-report on their use of quantitative measurements (metric). RESULTS: Among 439 respondents, metric rheumatologists (58%) were more likely to be in group practice and to use tumor necrosis factor inhibitors. The quantitative tools most commonly used were the Health Assessment Questionnaire (35.5%) and the Routine Assessment of Patient Index Data 3 (27.1%). Reasons for not measuring included time needed and electronic availability. Based on simulated case scenarios, providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic. CONCLUSION: Routine use of quantitative measurement for patients in the United States with RA is increasing over time but remains low.
30005689 Prediction of primary non-response to methotrexate therapy using demographic, clinical and 2018 Jul 13 BACKGROUND: Methotrexate (MTX) remains the disease-modifying anti-rheumatic drug of first choice in rheumatoid arthritis (RA) but response varies. Predicting non-response to MTX could enable earlier access to alternative or additional medications and control of disease progression. We aimed to identify baseline predictors of non-response to MTX and combine these into a prediction algorithm. METHODS: This study included patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre prospective observational study of patients with RA or undifferentiated polyarthritis, commencing MTX for the first time. Non-response to MTX at 6 months was defined as "no response" using the European League Against Rheumatism (EULAR) response criteria, discontinuation of MTX due to inefficacy or starting biologic therapy. The association of baseline demographic, clinical and psychosocial predictors with non-response was assessed using logistic regression. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. RESULTS: Of 1050 patients, 449 (43%) were classified as non-responders. Independent multivariable predictors of MTX non-response (OR (95% CI)) were rheumatoid factor (RF) negativity (0.62 (0.45, 0.86) for RF positivity versus negativity), higher Health Assessment Questionnaire score (1.64 (1.25, 2.15)), higher tender joint count (1.06 (1.02, 1.10)), lower Disease Activity score in 28 joints (0.29 (0.23, 0.39)) and higher Hospital Anxiety and Depression Scale anxiety score (1.07 (1.03, 1.12)). The optimism-corrected AUC was 0.74. CONCLUSIONS: This is the first model for MTX non-response to be developed in a large contemporary study of patients commencing MTX in which demographic, clinical and psychosocial predictors were considered. Patient anxiety was a predictor of non-response and could be addressed at treatment commencement.
28600618 Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis. 2018 Jan Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.
29478512 Protein Carbamylation: Chemistry, Pathophysiological Involvement, and Biomarkers. 2018 Protein carbamylation refers to a nonenzymatic modification, which consists in the binding of isocyanic acid on protein functional groups. This reaction is responsible for the alteration in structural and functional properties of proteins, which participate in their molecular aging. Protein molecular aging is now considered a molecular substratum for the development of chronic and inflammatory diseases, including atherosclerosis, chronic kidney disease, or rheumatoid arthritis. As a consequence, carbamylation-derived products have been proposed as interesting biomarkers in various pathological contexts and appropriate analytical methods have been developed for their quantification in biological fluids. The purpose of this review is (i) to describe the biochemical bases of the carbamylation reaction, (ii) to explain how it contributes to protein molecular aging, (iii) to provide evidence of its involvement in aging and chronic diseases, and (iv) to list the available biomarkers of carbamylation process and the related analytical methods.
29417713 Person-centred care in nurse-led outpatient rheumatology clinics: Conceptualization and in 2018 Jun BACKGROUND: Person-centred care (PCC) is considered a key component of effective illness management and high-quality care. However, the PCC concept is underdeveloped in outpatient care. In rheumatology, PCC is considered an unmet need and its further development and evaluation is of high priority. The aim of the present study was to conceptualize and operationalize PCC, in order to develop an instrument for measuring patient-perceived PCC in nurse-led outpatient rheumatology clinics. METHODS: A conceptual outpatient PCC framework was developed, based on the experiences of people with rheumatoid arthritis (RA), person-centredness principles and existing PCC frameworks. The resulting framework was operationalized into the PCC instrument for outpatient care in rheumatology (PCCoc/rheum), which was tested for acceptability and content validity among 50 individuals with RA attending a nurse-led outpatient clinic. RESULTS: The conceptual framework focuses on the meeting between the person with RA and the nurse, and comprises five interrelated domains: social environment, personalization, shared decision-making, empowerment and communication. Operationalization of the domains into a pool of items generated a preliminary PCCoc/rheum version, which was completed in a mean (standard deviation) of 5.3 (2.5) min. Respondents found items easy to understand (77%) and relevant (93%). The Content Validity Index of the PCCoc/rheum was 0.94 (item level range, 0.87-1.0). About 80% of respondents considered some items redundant. Based on these results, the PCCoc/rheum was revised into a 24-item questionnaire. CONCLUSIONS: A conceptual outpatient PCC framework and a 24-item questionnaire intended to measure PCC in nurse-led outpatient rheumatology clinics were developed. The extent to which the questionnaire represents a measurement instrument remains to be tested.
30345719 Back to the basics: Understanding joint swelling and tenderness at the wrist in rheumatoid 2019 Jan AIM: To compare ultrasound-detected inflammation with clinical manifestations at the wrist in rheumatoid arthritis (RA). METHOD: Wrists assessed serially by assessors blinded to ultrasound findings were categorized into 4 groups: 1 = S0T0 (not swollen; not tender); 2 = S0T1 (not swollen; tender); 3 = S1T0 (swollen; not tender); 4 = S1T1 (swollen; tender). Ultrasound synovitis and tenosynovitis were graded semi-quantitatively (0-3) and dichotomously (0 or 1), respectively. The (a) power Doppler (PD), gray-scale (GS) and combined (PD + GS) ultrasound (CUS) scores and (b) their positivity (score > 0) were analyzed using a general linear repeated measures mixed model (a) assuming Gaussian errors and (b) with binary distribution and logit link, respectively. Pairwise comparisons among wrist groups were performed within context of the models. RESULTS: In 122 wrist assessments (baseline = 64; 3 months = 58) from 32 treated RA patients (87.5% female; mean disease duration 42.8 months), significant differences among groups for (a) scores were: 4 vs 1 (PD, P = 0.0031; GS, P = 0.0159; CUS, P = 0.0045), 4 vs 2 (PD, P = 0.0176; GS, P = 0.0160; CUS, P = 0.0074), and 4 vs 3 (CUS, P = 0.0374); and (b) positivity were: 4 vs 1 (PD, P = 0.0007), 4 vs 2 (PD, P = 0.0234), and 3 vs 1 (PD, P = 0.0202). No significant differences in results were found for groups 2 vs 1. No significant effects were attributable to differences in wrist side or follow-up visit. CONCLUSION: Ultrasound detected substantial inflammation when wrist joint swelling and tenderness are both present. Joint swelling without tenderness is associated with significantly more frequent PD detection. Without swelling, joint tenderness is not associated with a significantly greater degree of ultrasound-detected inflammation.
29281812 Dynamic joint stiffness of the ankle in healthy and rheumatoid arthritis post-menopausal w 2018 Feb The purpose of this study was to compare rheumatoid arthritis post-menopausal women (RAPW) with pathological involvement of the lower limb joints and age-matched healthy post-menopausal women (AHPW) in regard to the dynamic joint stiffness of the ankle (DJS(ankle)) during the stance phase of gait. Data were collected from 18 RAPW and 18 AHPW. Gait was assessed by a three-dimensional motion analysis system synchronised with a force plate. Subjects walked barefoot at natural and self-selected speed, performing 14 valid trials (comprising 7 left and 7 right foot-steps on a force plate). The stance phase was split into three sub-phases that corresponded to the three angular displacements of the ankle that occurred during this phase, namely, controlled plantar flexion (CPF), controlled dorsiflexion (CDF), and powered plantar flexion (PPF). A linear model represented each sub-phase and computed DJS(ankle). Model fitting was assessed by the coefficient of determination (R(2)). The coefficient of variation (CV) was used to assess intra-individual variability. In all sub-phases, R(2) values for both groups were higher than 0.85. There were no differences in the R(2) values among groups. RAPW showed a higher DJS(ankle) during the CPF (p < 0.05). CDF and PPF yielded no differences among groups. During CPF, RAPW yielded a higher CV for DJS(ankle) (p < 0.01). RAPW also yielded lower ankle angular displacements during CPF and PPF (p < 0.05). Findings suggested that the stance phase of RAPW and AHPW can be studied by a linear ankle 'moment of force -- angle' relationship. During CPF, RAPW exhibited excessive ankle stiffness and presented a higher intra-individual DJS(ankle) variability.
29692005 Extension Study of PF-05280586, a Potential Rituximab Biosimilar, Versus Rituximab in Subj 2018 Nov OBJECTIVE: This extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF-05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF-05280586 after transition from rituximab reference products to PF-05280586, and follow-up of biomarker and efficacy assessments. METHODS: Subjects were offered ≤3 additional courses of treatment of PF-05280586, with or without a single transition from rituximab in Europe (rituximab-EU; MabThera) or the US (rituximab-US; Rituxan) to PF-05280586. Each course comprised 2 intravenous infusions (1,000 mg on days 1 and 15, separated by 24 weeks [± 8 weeks]). RESULTS: Of 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B cells between groups, and no apparent relationship between infusion-related reactions and antidrug antibodies with or without single transition from rituximab reference products to PF-05280586. Long-term safety and tolerability of PF-05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment-emergent adverse events independent of single drug transition. The percentage of subjects with a low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study. CONCLUSION: This study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from rituximab reference products to PF-05280586, without increased immunogenicity on single transition.
29303701 Increased levels of serum histone H4 and activated protein C in patients with active rheum 2018 May OBJECTIVES: We aimed to examine the levels of serum H4 and activated protein C (APC) in rheumatoid arthritis (RA) and other autoimmune conditions, and investigate the associations between H4 or APC levels and disease activity indicators in RA. METHODS: Serum H4 and APC distribution was examined in samples from patients with RA, systemic lupus erythematosus (SLE), polymyositis (PM), and ankylosing spondylitis (AS), as well as in samples from healthy controls, using commercial ELISA kits. Associations of serum H4 or APC levels with disease variables in patients with RA were evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant capacity of APC against RA and non-RA. RESULTS: The patients with RA, PM, and AS showed higher serum levels of H4 and APC than those from the healthy control individuals, while the SLE patients showed higher serum levels of APC only. Moderate positive correlations between H4 levels and absolute neutrophil count (ANC), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), brinogen (FIB), D-dimer (DD), and complement fraction 3 (C3) were observed. Positive correlations between APC levels and PLT, RF, DD, or DAS28 were additionally found. ROC curve analysis revealed that APC discriminated well between RA and non-RA. CONCLUSIONS: H4 and APC concentrations are elevated in patients with chronic in ammatory autoimmune diseases. The observed associations between H4 and APC and disease variables in patients with RA support a role for H4 and APC in the in ammatory process of the disease.
29425827 Association of HLA-DPB1 polymorphisms with rheumatoid arthritis: A systemic review and met 2018 Apr BACKGROUND: The current reports on the association between HLA-DPB1 alleles and rheumatoid arthritis (RA) results were controversial. Thus, we conducted a meta-analysis to assess whether DPB1 alleles are associated with increased risk of rheumatoid arthritis. METHODS: Systematic searches on PubMed, Embase, Elsevier, CNKI (China National Knowledge Infrastructure), Wanfang data and Cochrane Library prior to July 2017 were performed. The pooled odds ratios (ORs) and 95% confidence interval (95% CI) was used to assess the association between frequencies of DPB1 alleles and RA patients. RESULTS: Eight studies with 592 cases and 935 controls were included in this meta-analysis. Overall, the pooled ORs showed that frequencies of DPB1*0401 and *0601 were higher in the RA group compared with controls (*0401: OR: 1.586, 95%CI: 1.296-1.941, P<0.001; *0601: OR: 1.921, 95%CI: 1.142-3.229, P=0.014). Whereas, the frequencies of DPB1*0101, *0402 and *0501 were lower in the RA control than the controls (*0101: OR: 0.691, 95%CI: 0.481-0.993, P=0.046; *0402: OR: 0.707, 95%CI: 0.555-0.902, P=0.005; *0501: OR: 0.502, 95%CI: 0.329-0.767, P=0.001). No associations were observed for DPB1*0201, *0202, *0301 and *0901 (*0201: OR: 1.129, 95%CI: 0.882-1.446, P = 0.335; *0202: OR: 0.840, 95%CI: 0.940-1.441, P = 0.527; *0301: OR: 0.769, 95%CI: 0.577-1.026, P = 0.074; *0901: OR: 1.221, 95% CI: 0.541-2.755, P = 0.630). CONCLUSIONS: This meta-analysis demonstrates that high frequency expression of DPB1*0401 and *0601 are significantly associated with susceptibility to RA, it may be a risk factor for occurrence of RA. Low frequency expression of DPB1*0101, *0402 and *0501 may be negatively associated with RA, it may be a protective factor for occurrence of RA.
28882464 Metacarpophalangeal joint of the thumb arthrodesis using intramedullary interlocking screw 2018 Sep The study objective was to assess the results of a thumb metacarpophalangeal joint (MCPJ) arthrodesis using intramedullary interlocking screws at 25°, XMCP ™ (Extremity Medical, Parsippany, NJ). Radiographs evaluated the angle of arthrodesis, time of fusion and fixation of the implant. Clinical and functional outcomes were assessed using the DASH questionnaire and the VAS scale. Any complications found during surgery or the follow-up period were noted. We studied 9 patients. The mean follow-up was 27.6 months. Patients showed clinical and radiological evidence of fusion in an average of 8 weeks, the angle of fusion was 25°. There were no complications and no implant had to be removed. The XMCP™ system provides a reliable method for MCPJ arthrodesis for several indications and can be used with other procedures in the complex hand.
29148403 Treatment patterns in rheumatoid arthritis after discontinuation of methotrexate: data fro 2018 Mar OBJECTIVES: In active rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), guidelines support adding or switching to another conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or a biologic DMARD (bDMARD). The purpose of this analysis was to describe treatment practices in routine care and to evaluate determinants of regimen selection after MTX discontinuation. METHODS: Biologic-naïve patients in the Ontario Best Practice Research Initiatives registry discontinuing MTX due to primary/secondary failure, adverse events, or patient/physician decision were included. RESULTS: Of 313 patients discontinuing MTX, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) on double, and 55 (17.6%) on multiple csDMARDs. Patients on MTX monotherapy were older than patients on double or multiple csDMARDs (p=0.013), less likely to have joint erosions (p=0.009) and had lower patient global assessment (p=0.046) at MTX discontinuation. Post-MTX discontinuation, 169 (54.0%) transitioned to, or added new DMARD(s) (new csDMARD(s): 139 [44.4%]; bDMARD: 30 [9.6%]), and 144 (46.0%) opted for no new DMARD treatment. Patients on MTX monotherapy transitioning monotherapy, whereas patients on combination csDMARDs switched more to new csDMARDs and bDMARD combination therapy. Early RA (adjOR [95%CI]: 3.07 [1.40-6.72]) and treatment with multiple csDMARDs vs. MTX monotherapy (4.15 [1.35-12.8]) at MTX discontinuation were significant predictors of transitioning to or adding new csDMARD(s)/bDMARD treatment versus opting for no new DMARD treatment. CONCLUSIONS: Differences in subsequent treatment patterns exist between patients discontinuing MTX when used as monotherapy versus in combination with other csDMARDs where the former are more likely to use a subsequent monotherapy treatment.
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.
29733234 Glycosylation of random IgG distinguishes seropositive and seronegative rheumatoid arthrit 2018 May The N-glycosylation of human immunoglobulins, especially IgGs, plays a critical role in determining affinity of IgGs towards their effector (pro- and anti-inflammatory) receptors. However, it is still not clear whether altered glycosylation is involved in only antibody-dependent disorders like seropositive rheumatoid arthritis (RA) or also in pathologies with similar clinical manifestations, but no specific autoantibodies like seronegative RA. The clarification of that uncertainty was the aim of the current study. Another study aim was the detection of specific glycan forms responsible for altered exposure of native glycoepitopes. We studied sera from seropositive RA (n = 15) and seronegative RA (n = 12) patients for exposure of glycans in native IgG molecules, followed by determination of specific glycans by capillary electrophoresis with laser-induced fluorescent detection (CE-LIF). Aged-matched groups of normal healthy donors (NHD) and samples of intravenous immunoglobulin IgG preparations (IVIG) served as controls. There was significantly stronger binding of Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) lectins towards IgG from seropositive RA compared to seronegative RA or NHD. CE-LIF analysis revealed statistically significant increases in bisecting glycans FA2BG2 (p = .006) and FABG2S1 (p = .005) seropositive RA, accompanied by decrease of bisecting monogalactosylated glycan FA2(6)G1 (p = .074) and non-bisecting monosialylated glycan FA2(3)G1S1 (p = .055). The results suggest that seropositive RA is distinct from seronegative RA in terms of IgG glycan moieties, attributable to specific immunoglobulin molecules present in seropositive disease. These glycans were determined to be bisecting GlcNAc-bearing forms FA2BG2 and FABG2S1, and their appearance increased the availability of LCA and AAL lectin-binding sites in native IgG glycoepitopes.