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ID PMID Title PublicationDate abstract
30248041 Evaluation of rational drug use knowledge level in patients with musculoskeletal disorders 2019 BACKGROUND: For treatment of chronic musculoskeletal disorders pains to be successful, drug interventions are required. OBJECTIVE: In this study, we aimed to evaluate the Rational Drug Use Knowledge Level (RDUKL) in patients with musculoskeletal disorders and some relevant factors. METHOD: The study was carried out in October 2017 on patients treated in the Physical Therapy Rehabilitation Hospital in Turkey. The prepared questionnaire and RDUKL scale were administered to 239 patients by face-to-face interviews. The ANOVA test, chi-squared test and logistic regression model were used for the statistical evaluation. RESULTS: Forty-three percent of the study group was found to have Rational Drug Use Knowledge (RDUK). The patients who used medicines under family supervision had twice as much RDUK as those who did not use medicines under family supervision, and those who were university graduates had six times as much RDUK as those who had primary education or below. Scale score was found to be low in patients with fibromyalgia and high in patients with rheumatoid arthritis (p< 0.05). CONCLUSION: RDUKL was found to be low in the group with chronic diseases and high average age. Besides training, it is important to provide patients with family support about their illness and its treatment. Thus, positive contributions can be made to the increase of the RDUKL.
30269048 Ultra-low-dose CT detects synovitis in patients with suspected rheumatoid arthritis. 2019 Jan PURPOSE: To prove the feasibility and measure the diagnostic accuracy of contrast-enhanced ultra-low-dose CT (ULD-CT) for the depiction of inflammatory soft-tissue changes (synovitis, tenosynovitis and peritendonitis) in patients with arthritis of the hand. MATERIALS AND METHODS: In this institutional review board-approved study, 36 consecutive patients over the age of 50 with suspected rheumatoid arthritis underwent ULD-CT (estimated radiation exposure <0.01  mSv) and MRI of the hand with weight-adapted intravenous contrast administration. ULD-CT subtraction and MR images were assessed for synovitis, tenosynovitis and peritendonitis by three readers using a modified Rheumatoid Arthritis MRI Score (RAMRIS). Patients were asked which modality they would prefer for future examinations. Sensitivity and specificity of ULD-CT for detection of inflammatory changes were calculated using MRI as standard of reference. The sum scores were correlated using Pearson's r. RESULTS: All 36 patients showed synovitis in MRI. ULD-CT had 69% sensitivity on the patient level and 65% on the joint level with 87% specificity. Sensitivity was higher in patients with more severe inflammation (80% for MRI RAMRIS >1). There was almost perfect correlation between the modified RAMRIS sum scores of ULD-CT and MRI (Pearson's r=0.94). Regarding preferences for future examinations, 85% preferred ULD-CT over MRI. ULD-CT detected more differential diagnoses than MRI (8 vs 2/12). CONCLUSION: Contrast-enhanced ULD-CT of the hand allows for depiction of soft-tissue inflammation at the hand and can be achieved using very low radiation exposure (<0.01 mSv). ULD-CT may evolve to a fast and comfortable alternative to MRI, although it is not as sensitive as MRI for detecting mild disease.
30677239 Clinical outcomes of patients with active rheumatoid arthritis with normal acute phase rea 2019 May AIM: Despite high clinical disease activity, some patients with active rheumatoid arthritis (RA) have normal acute phase reactant (APR) values. This study aimed to determine the clinical outcomes of active RA patients with normal APR values. METHOD: Of 5376 patients with RA enrolled in the Korean observational study network for arthritis (KORONA) registry, 400 patients with disease duration of <2 years who had Clinical Disease Activity Index (CDAI) score of >2.8 at baseline, biologic-naïve, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) drawn at both baseline and 2-year follow-up visits were identified. Patients were grouped according to baseline APR levels: normal APRs, one APR elevated, and both APRs elevated. RESULTS: Baseline tender and swollen joint counts, mean CDAI and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were significantly lower in the normal APRs group compared with APR-elevated groups (P < 0.0001). At 2-year follow-up, mean CDAI scores, HAQ-DI, and percentage of the patient achieving remission were not significantly different between the normal APRs group compared with the APR-elevated groups regardless of the baseline disease activity. However, in patients with baseline CDAI moderate to high disease activity, the normal APRs group less frequently required initiation of the biologic disease-modifying anti-rheumatic drugs compared with the APR-elevated groups (P = 0.044). CONCLUSION: Active RA patients with normal APR values have milder disease presentation, but similar clinical outcomes to those with elevated APRs.
30658176 Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis 2019 Jun Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59-79% of cohort participants) and resolving pain (19-27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3-2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6-1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PERSPECTIVE: Immunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.
31113467 Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis. 2019 May 21 BACKGROUND: Numerous preclinical studies have revealed a critical role of cysteine-rich 61 (Cyr61) in the pathogenesis of rheumatoid arthritis (RA). But there is little literature discussing the clinical value of circulation Cyr61 in RA patients. The aim of our study is to investigate the serum Cyr61 level and its association with disease activity in RA patients. METHODS: A training cohort was derived from consecutive RA patients who visited our clinic from Jun 2014 to Nov 2018. Serum samples were obtained at the enrollment time. To further confirm discovery, an independent validation cohort was set up based on a registered clinical trial. Paired serum samples of active RA patients were respectively collected at baseline and 12 weeks after uniformed treatment. Serum Cyr61 concentration was detected by enzyme-linked immunosorbent assay. The comparison of Cyr61 between RA patients and controls, the correlation between Cyr61 levels with disease activity, and the change of Cyr61 after treatment were analyzed by appropriate statistical analyses. RESULTS: A total of 177 definite RA patients and 50 age- and gender-matched healthy controls were enrolled in the training cohort. Significantly elevated serum Cyr61 concentration was found in RA patients, demonstrating excellent diagnostic ability to discriminate RA from healthy controls (area under the curve (AUC) = 0.98, P <  0.001). In addition, the Cyr61 level in active RA patients was significantly lower than that in patients in remission/low disease activity, and it was inversely correlated with composite disease activity scores and almost all of the components in statistic. Further study in the validation cohort (n = 77) showed a significant increase of the Cyr61 level at 12 weeks in ACR responders (ACR20/50/70), while no significant change of the Cyr61 level from baseline was observed in non-responders. CONCLUSIONS: Serum Cyr61 levels were remarkably increased in RA patients compared with those in healthy controls. The Cyr61 concentration was inversely correlated with RA disease activity and upregulated in those therapeutic responders. TRIAL REGISTRATION: Combination Therapy Prevents the Relapse of RA, NCT02320630 . Registered 19 December 2014.
29885039 Responsiveness of Patient-Reported Outcomes Measurement Information System Measures in Rhe 2019 Apr OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS) is a calibrated item bank used to assess patient-reported outcomes across multiple domains. The purpose of this study was to describe the performance of selected PROMIS measures in patients with rheumatoid arthritis (RA) with active disease who were initiating a disease-modifying antirheumatic drug (DMARD). METHODS: Participants in an ongoing prospective observational study completed 8 PROMIS measures before and after DMARD initiation. Linear regression models were performed to identify cross-sectional associations between baseline PROMIS measures and disease activity, measured using the Clinical Disease Activity Index (CDAI). Paired t-tests were performed to evaluate responsiveness after 12 weeks of DMARD treatment. Associations between changes in PROMIS measures and changes in the CDAI score were assessed using linear regression. RESULTS: Among the 156 participants who completed the first study visit, the mean ± SD baseline CDAI score was 25.5 ± 14.0. Baseline scores for PROMIS measures of physical health, pain, and sleep were associated with the baseline CDAI score (P ≤ 0.05). Among the 106 participants with 12-week data, all PROMIS scores improved after DMARD initiation (P ≤ 0.05). With the exception of depression, changes in all assessed PROMIS measures were correlated with changes in the CDAI score (standardized βs from |0.23| to |0.38|). CONCLUSION: These data provide support for the utility of PROMIS measures for the assessment of physical and mental health in individuals with active RA. All PROMIS measures improved significantly after DMARD initiation, with the magnitudes of association between changes in PROMIS measures and changes in the CDAI score in the low-to-moderate range.
31505424 miR-410-3p regulates proliferation and apoptosis of fibroblast-like synoviocytes by target 2019 Nov In our previous study, miR-410-3p had been confirmed to regulate inflammatory cytokine release in rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). However, other biological functions of miR-410-3p in RA FLSs still remain unexplored. In the present study, we focused on the effect of miR-410-3p on proliferation, apoptosis, and cell cycle of RA FLSs, and explored the potential underlying mechanism. miR-410-3p mRNA levels in the synovium and FLSs of patients with RA and of healthy controls were quantitated by RT-qPCR. The levels of miR-410-3p were reduced in both synovium and FLSs from patients with RA. Next, we focused on the roles of miR-410-3p in cell viability, apoptosis, and cell cycle, by transfecting miR-410-3p mimics and inhibitor into RA FLSs, and conducting CCK-8 assay, EdU staining and flow cytometry. Results showed that miR-410-3p up-regulation suppressed proliferation, promoted apoptosis and G1-S phase transition while miR-410-3p down-regulation had opposite effects. YY1 was verified as a direct target gene of miR-410-3p through the luciferase reporter system; YY1 up-regulation was able to rescue the effects of miR-410-3p in RA FLSs. Taken together, our current findings might provide a potential therapeutic target for RA.
30315988 Update of French society for rheumatology recommendations for managing rheumatoid arthriti 2019 Mar The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and non-pharmacological treatments. The recommendations deal with the diagnostic strategy for RA, treatment targets, management organization, drug selection based on the treatment line and prognostic factors, management of remissions, and global patient management. Disease-modifying anti-rheumatic drug (DMARD) therapy should be started as early as possible. Validated composite scores should be determined at regular intervals to assess disease activity - according to the tight disease control concept - to achieve the treatment target, i.e., a remission. Methotrexate is the recommended first-line DMARD. The treatment should be optimized when methotrexate is poorly tolerated or inadequately effective. While waiting for conventional synthetic DMARDs to take effect, glucocorticoid therapy can be used, for a brief period to keep the cumulative dose low. When a sustained remission without structural progression is achieved in a patient who is not taking glucocorticoid therapy, targeted therapy de-escalation according to tight disease control principles should be considered. Patients should be periodically screened for comorbidities and their risk factors, which should be evaluated and treated.
30634089 Beneficio económico de los ensayos clínicos controlados patrocinados: El gasto evitable 2019 Dec OBJECTIVES: To estimate the following: (1) the avoidable cost of biologic (bDMARDs) and conventional synthetic Rheumatoid Arthritis (RA) modifying antirheumatic drugs (csDMARDs) during controlled clinical trials (CCTs), their extension period, and for bDMARDs in post study drug programs; and (2) to evaluate the impact on health insurances. METHODS: We analyzed 13 CCTs (233 patients) that evaluated bDMARDs. Avoidable cost was what the health insurance should have paid if the patient had not received the medication from the CCT sponsor and was estimated with a micro-costing approach (bottom-up method). Results were expressed as mean ± standard deviation (SD) or percentages. Approved by the Ethics Committee. RESULTS: Mean age was 50.62 SD 11.8 years, 84% were women, 72% (n = 166) had health insurance. The mean annual cost of bDMARDs was US$ 30 567.40 while the cost for csDMARDs was US$ 104.90 during the CCTs. The mean annual cost in extension periods and post study drug programs for bDMARDs was US$ 36 016.20 and for csDMARs during the extension period was US$ 81.70. The avoidable cost for public health insurances exceeded one million dollars per year. CONCLUSION: This work describes for the first time in Argentina the significant economic benefit that may represent for RA patients' health insurances the participation in CCTs with bDMARDs. It shows that during the execution of the CCT, its extension periods, or post study access programs, while medication provision is guaranteed, the economic burden imposed by the treatment of the RA is relieved.
30843355 Elevated expression of interleukin-37 in patients with rheumatoid arthritis. 2019 Jun AIM: This study aims to discuss plasma and messenger RNA (mRNA) levels of interleukin (IL)-37 in rheumatoid arthritis (RA) patients and evaluate the potential of plasma IL-37 as a biomarker for RA. METHOD: Plasma IL-37 levels and IL-37 mRNA relative concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). We discussed the association of IL-37 levels and clinical, laboratory parameters in RA patients in a training cohort. Plasma IL-37 levels were tested for discriminatory capacity by receiver operating characteristic (ROC) curve analysis. We then validated plasma IL-37 expression in a cohort of 598 patients (230 RA, 107 systemic lupus erythematosus [SLE], 100 osteoarthritis [OA], 62 gout, 51 primary Sjögren's syndrome [pSS], 48 ankylosing spondylitis [AS]). RESULTS: Both plasma levels of IL-37 and mRNA levels of IL-37 were elevated in RA patients compared to those in healthy controls in the training cohort, and there was a good diagnostic ability to predict RA (area under the curve [AUC] = 0.97). Plasma IL-37 levels were significantly related to Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) (r(s)  = 0.459, P < 0.001). The levels of IL-37 mRNA were related to plasma IL-37 levels (r(s)  = 0.642, P < 0.001), DAS28-ESR (r = 0.641, P < 0.001) and C-reactive protein (r(s)  = 0.603, P < 0.001). In the validation cohort, when plasma IL-37 in RA patients compared with that in SLE, OA, gout, pSS and AS patients, the AUC was 0.86, 0.87, 0.91, 0.87, 0.92, respectively. CONCLUSION: IL-37 expression was increased in RA patients, and correlated with disease activity. IL-37 may be a biomarker for the diagnosis of RA.
30101636 Anti-cyclic citrullinated peptide antibodies, 28-joint Disease Activity Score, and magneti 2019 Jan OBJECTIVE: To investigate the clinical and radiographic status, and to identify baseline predictors of functional status and erosive progression at 11 years' follow-up of early rheumatoid arthritis (RA) patients. METHODS: Patients enrolled in the Danish investigator-initiated randomized controlled CIMESTRA trial, which investigated a 2 year treat-to-target intervention with methotrexate and intra-articular glucocorticoids with or without cyclosporine, were followed up. The 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) score, and total Sharp van der Heijde score (TSS) were assessed at baseline and 11 years. Baseline magnetic resonance imaging (MRI) of unilateral wrists was scored (OMERACT RAMRIS). Multivariable linear regression analyses of baseline variables [TSS, HAQ, DAS28, age, anti-cyclic citrullinated peptide (anti-CCP) status, gender, MRI erosion score, MRI synovitis score, MRI bone marrow oedema score] were performed in 96 patients with HAQ(11yrs) and ∆TSS(0-11yrs) as dependent variables. Since outcomes were similar in the two treatment arms, data were pooled. RESULTS: In total, 120 of 160 patients completed 11 years' follow-up. They were 63 (55-72) years old, 68% were in DAS28 remission (≤ 2.4), HAQ(11yrs) was 0.25 (0-0.75), mean ∆TSS(0-11yrs) was 0.96 ± 1.52 units/year; 53%, 20%, and 27% received conventional treatment, biologics, and no treatment, respectively; and 34% had not progressed radiographically since baseline. Increased DAS28 (p = 0.02) and anti-CCP (p = 0.03) predicted HAQ(11yrs), whereas anti-CCP (p = 0.03) and MRI bone marrow oedema (p = 0.01) predicted ∆TSS(0-11yrs) in multivariable analyses. CONCLUSIONS: Early and strict synovitis suppression with methotrexate and intra-articular glucocorticoids led to persistently high remission rates and limited erosive progression at 11 years. In this well-treated cohort, baseline anti-CCP status, DAS28, and MRI bone marrow oedema predicted functional status and/or erosive progression.
30148433 A combination model to predict relapse and successful conventional DMARDs de-escalation in 2019 Jan OBJECTIVES: To determine the long-term outcomes of RA patients in sustained clinical remission under different therapeutic strategies and explore the risk factors to relapse. METHODS: RA patients in sustained clinical remission (DAS28(CRP) ≤2.6 for at least 6 months) were enrolled. Their baseline clinical features, ultrasonography and x-ray of hands were collected. The usage of conventional synthetic disease-modified anti-rheumatic drugs (csDMARDs) at baseline and every follow-up visits were recorded. Patients were divided into maintain-therapy group or de-escalate-therapy group according to their treatment during follow-up. The time-point of follow-up visits reaching 2 years or flare (DAS28(CRP)>2.6) was defined as the endpoint of the study. The risk factors to predict flare was analysed by logistic regression model. RESULTS: 94 patients were enrolled in the study, with 59 in de-escalate-therapy group and 35 in maintain-therapy group. During an average of 20.8 months of follow-up, 40 (42.6%) patients relapsed, with 31 (52.5%) from de-escalate-therapy group and 9 (25.7%) from maintain-therapy group. De-escalate-therapy increased the risk of flare by 2.3 times (OR=3.38, p=0.044). Baseline DAS28(CRP) (OR=6.97, p=0.038), presence of subclinical synovitis (OR=3.67, p=0.024), combination of 2 csDMARDs (OR=3.72, p=0.030) were the risk factors for relapse, and the best cut-off value of DAS28(CRP) for relapse prediction through ROC curve was 1.82. Taking the three parameters into the model for a combined prediction probability, the area under the ROC curve was 0.722 (95% CI 0.61, 0.82, p=0.000). CONCLUSIONS: De-escalation therapy was associated with higher risk of relapse in RA patients with sustained clinical remission. A combination model of DAS28(CRP)<1.82 and no subclinical synovitis may help to predict successful csDMARDs reduction in RA patients with sustained clinical remission receiving csDMARDs monotherapy.
31455869 Mechanisms of lung disease development in rheumatoid arthritis. 2019 Oct Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes joint inflammation and damage. Extra-articular manifestations occur in many patients and can include lung involvement in the form of airway or parenchymal inflammation and fibrosis. Although the pathophysiology of articular RA has been extensively investigated, the mechanisms causing airway and parenchymal lung disease are not well defined. Infections, cigarette-smoking, mucosal dysbiosis, host genetics and premature senescence are all potentially important contributors to the development of lung disease in patients with RA. RA-associated lung disease (which can predate the onset of articular disease by many years) probably originates from chronic airway and alveolar epithelial injury that occurs in an individual with a genetic background that permits the development of autoimmunity, leading to chronic inflammation and subsequent airway and lung parenchymal remodelling and fibrosis. Further investigations into the specific mechanisms by which lung disease develops in RA will be crucial for the development of effective therapies. Identifying mechanisms by which environmental and host factors cooperate in the induction of autoimmunity in the lung might also help to establish the order of early events in RA.
30733963 The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retent 2019 INTRODUCTION: To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). METHODS: The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. RESULTS: 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. CONCLUSIONS: Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.
31372762 Beyond the antibodies: serum metabolomic profiling of myasthenia gravis. 2019 Aug 1 INTRODUCTION: Myasthenia gravis (MG) is a chronic, potentially debilitating autoimmune disease characterized by weakness and rapid fatigue of the voluntary muscles that worsens on exertion. Left untreated, MG symptoms may cause significant morbidity or even death. To date, no robust biological marker is available to follow the course of the disease. Therefore, new diagnostic approaches and biological markers are essential not only for improved diagnosis of the disease but for improved outcomes. OBJECTIVES: The present study applied a two-control, multi-label metabolomics profiling approach as a potential strategy for the identification of biomarkers unique to myasthenia gravis (MG). METHODS: Metabolic analyses using acid- and dansyl-labelled serum from seropositive MG (n = 46), rheumatoid arthritis (RA) (n = 23) and healthy controls (HC) (n = 49) were performed on samples from adult patients presenting to the University of Alberta Hospital neuromuscular and rheumatology clinics. Comparisons between patients with MG vs. HC, and RA vs. HC were made using univariate and multivariate statistics. RESULTS: Serum biomarker patterns were statistically significantly different between groups. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models exhibited considerable distinction between all groups. Metabolites were then filtered to remove peak pairs common to both disease cohorts. Combined metabolite panels revealed clear separation between MG and HC for both library-matched (AUROC: 0.92 ± 0.03) and highest AUC patients (AUROC: 0.94 ± 0.05). CONCLUSION: In patients presenting to the clinic with seropositive MG, metabolomic profiling is capable of distinguishing patients with disease from those without. These results provide an important first step towards a potential biomarker for improving MG identification.
30886733 Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rh 2019 OBJECTIVE: To compare efficacy and safety of subcutaneous sarilumab 200 mg and 150 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARDs) versus other targeted DMARDs+csDMARDs and placebo+csDMARDs, in inadequate responders to csDMARDs (csDMARD-IR) or tumour necrosis factor α inhibitors (TNFi-IR). METHODS: Systematic literature review and network meta-analyses (NMA) conducted on 24 week efficacy and safety outcomes: Health Assessment Questionnaire Disability Index, modified total sharp score (mTSS, including 52 weeks), American College of Rheumatology (ACR) 20/50/70, European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28)<2.6; serious infections/serious adverse events (including 52 weeks). RESULTS: 53 trials were selected for NMA. csDMARD-IR: Sarilumab 200 mg+csDMARDs and 150 mg+csDMARDs were superior versus placebo+csDMARDs on all outcomes. Against most targeted DMARDs, sarilumab 200 mg showed no statistically significant differences, except superiority to baricitinib 2 mg, tofacitinib and certolizumab on 24 week mTSS. Sarilumab 150 mg was similar to all targeted DMARDs. TNFi-IR: Sarilumab 200 mg was similar to abatacept, golimumab, tocilizumab 4 mg and 8 mg/kg intravenously and rituximab on ACR20/50/70, superior to baricitinib 2 mg on ACR50 and DAS28<2.6 and to abatacept, golimumab, tocilizumab 4 mg/kg intravenously and rituximab on DAS28<2.6. Sarilumab 150 mg was similar to targeted DMARDs but superior to baricitinib 2 mg and rituximab on DAS28<2.6 and inferior to tocilizumab 8 mg on ACR20 and DAS28<2.6. Serious adverse events, including serious infections, appeared similar for sarilumab versus comparators. CONCLUSIONS: Results suggest that in csDMARD-IR and TNFi-IR (a smaller network), sarilumab+csDMARD had superior efficacy and similar safety versus placebo+csDMARDs and at least similar efficacy and safety versus other targeted DMARDs+csDMARDs.
30951251 Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid A 2019 Sep OBJECTIVE: To evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD). METHODS: We investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules. RESULTS: Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules. CONCLUSION: Active articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.
31090187 Increased risk of opportunistic infection in early rheumatoid arthritis. 2019 Jul AIM: To estimate incidence rate (IR) and risk factors for opportunistic infections (OI) in early rheumatoid arthritis (RA) patients. METHODS: Retrospective cohorts were identified in the Korean National Claims Database. Incident RA cases were recruited in 2010 (n = 14 081). Follow up was ended at the time of development of new OI or at the date of last visit within 12 months of diagnosis. The IR and standardized incidence ratio (SIR) of OI in early and overall RA (n = 226 838) over a year were calculated. A multivariable regression model was used to identify risk factors for OI in early RA. RESULTS: The IR of OI in early and overall RA were 3.81/100 and 3.67/100 person-years, respectively. The SIR for OI in early RA was 1.14 (95% CI, 1.05-1.23). Herpes zoster (SIR = 1.12, 95% CI, 1.03-1.22) and candidiasis (SIR = 2.40, 95% CI, 1.55-3.54) were common in early RA. Age (50 < age ≤ 60 [OR 1.74, 95% CI, 1.30-2.33], 60 < age ≤ 70 [OR 1.85, 95% CI, 1.36-2.52], age > 70 [OR 1.89, 95% CI, 1.34-2.68]), female sex (OR 1.40, 95% CI, 1.12-1.74), comorbidities (one comorbidity [OR 1.53, 95% CI, 1.24-1.89], ≥ two comorbidities [OR 1.84, 95% CI, 1.47-2.29]), and corticosteroid use of 5 mg/d or more (OR 1.38, 95% CI, 1.13-1.69) were significantly associated with increased risk of OI in early RA. CONCLUSION: Opportunistic infections, especially for herpes zoster and candidiasis, tend to occur more often in early RA than in overall RA. Age, female sex, comorbidities and corticosteroid use are related to increased OI in early RA patients.
30690561 Prevalence and distribution of cartilage damage at the metacarpal head level in rheumatoid 2019 Jul 1 OBJECTIVES: To determine the prevalence and distribution of US-detected qualitative cartilage damage at metacarpal heads of patients with RA and hand OA. METHODS: Fifty-two RA patients and 34 patients with hand OA were enrolled. US examination of the metacarpal head cartilage from the II to V finger of both hands was performed. A total of 414 MCP joints in RA and 266 MCP joints in OA patients were scanned with a linear probe up to 22 MHz. Qualitative assessments using a previously described scoring system for cartilage damage were performed. The prevalence and distribution of cartilage damage were analysed. Multivariate regression analysis was used to determine the predictive value of age, gender, BMI, disease duration and the presence of RF and anti-CCP antibodies for US-detected cartilage damage. RESULTS: The metacarpal head cartilage was positive for cartilage damage in 35.7% (148/414) of MCP joints in RA and in 43.6% (116/266) of MCP joints in OA patients. In RA, the hyaline cartilage of the II and III metacarpal heads (bilaterally) was the most frequently affected. In OA, cartilage damage was more homogeneously distributed in all MCP joints. Multivariate regression analysis showed that age and disease duration, but not gender, BMI or autoantibody status, were independent predictors of US-detected cartilage damage in RA. CONCLUSION: Cartilage damage was found in more than one-third of the MCP joints in both RA and OA patients, and in RA patients, the II and III MCP joints were the most damaged.
31464236 Spectrum of glomerulonephritis in Egyptian patients with rheumatoid arthritis: A Universit 2019 Jul Rheumatoid arthritis (RA) is accompanied by a variety of nephropathies. It is often difficult to distinguish between disease-associated and drug-associated renal diseases. Three hundred and seventy-six RA patients with renal involvement were included in our study; they were subjected to full history and clinical examination, kidney function, 24-h urinary protein, and kidney biopsy. All our patients were on methotrexate, low dose steroids, and nonsteroidal anti-inflammatory drugs, in addition to the previous medications. About 79.3%, 20.7%, 6.9%, and 5.9% of our patients were on leflunomide, hydroxychloroquine, etanercept, and infliximab, respectively. Renal presentation was in the form of nephrotic syndrome (33.5%), persistent subnephrotic proteinuria (12.2%), persistent proteinuria and recurrent hematuria (13.3%), acute nephritis (23.9), recurrent hematuria (7.4%), and creatinine >1.5 mg/dL (10.6%). Renal biopsies were glomerular amyloidosis (28.1%), mesangioproliferative (19.1%), membranous (6.1%), crescent (16.8%), focal segmental glomerulosclerosis (18.6%), and minimal changes (11.7%). There was a statistically significant difference in the incidence of membranous nephritis between patients who took leflunomide, and hydroxychloroquine and those did not. Etanercept in our study seems not to be related to any form of renal involvement, while infliximab is related to focal segmental sclerosis and amyloidosis of tubulointerstitial type. Kidney involvement in RA is not a rare complication. Any type of histopathological changes can be present, with amyloidosis on top of the list. Hydroxychloroquine and leflunomide are accused in membranous nephropathy. Infliximab is associated with focal segmental sclerosis and amyloidosis of tubulointerstial type, and etanercept appear to be safe as regards kidney affection.