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ID PMID Title PublicationDate abstract
30321524 Utility of estimated glomerular filtration rate using cystatin C and its interpretation in 2018 Dec BACKGROUND: Patients with rheumatoid arthritis (RA) often have reduced muscle mass. Estimated glomerular filtration ratio using the serum cystatin C concentration (eGFRcys) is more accurate than eGFR using the serum creatinine (eGFRcreat) because cystatin C is not influenced by muscle mass, but glucocorticoid therapy may affect serum cystatin C concentration. METHODS: Fifty patients with RA were included in this study. Renal inulin clearance (Cin) was measured and compared with eGFRcreat, eGFRcys, or the mean of eGFRcreat and eGFRcys (eGFRavg). RESULTS: The mean creatine kinase (CK) concentration was low (36.8 ± 24.4 U/l).The eGFRcreat and eGFRcys regression lines were significantly different from y = x. The mean eGFRcreat value was significantly higher than Cin and that of eGFRcys was lower than Cin. The difference between eGFRcys and Cin was negatively correlated with daily PSL dose. The mean eGFRcys value of patients taking <10 mg PSL was not different from Cin and the eGFRcys regression line was not different from y = x. CONCLUSION: eGFRcys of patients taking a daily PSL dose ≥10 mg was inaccurate, while eGFRcys was underestimated. eGFRcys was more accurate than eGFRcreat or eGFRavg for patients taking a daily PSL dose of <10 mg.
30103715 Radiocarpal fusion and midcarpal resection interposition arthroplasty: long-term results i 2018 Aug 14 BACKGROUND: The aim of this retrospective study is to evaluate distal resection interposition arthroplasty of the wrist as a tool to restore mobility as well as to restore stability in severely destroyed wrist joints. METHODS: Thirty-four wrists in 28 rheumatoid arthritis patients were included. The mean follow-up time was 9 years after surgical treatment with clinical and radiological examination. The results were accessed based on a modification of Clayton ́s scoring system as well as a functional questionnaire. RESULTS: 71% patients were satisfied with pain, function and activities of daily life. Better results were reported by patients with a young age, early surgical intervention, a shorter duration of the disease, and lesser involvement of other joints. CONCLUSIONS: The results for radiocarpal arthrodesis were comparable to those of synovectomy or arthrodesis of the wrist. The results after total wrist joint arthroplasty varies probably as the result of different patient groups, implant types and evolution of prosthetic designs, and are not comparable with the present study.
30646250 Risk of Thyroxine-Treated Autoimmune Thyroid Disease Associated With Disease Onset in Pati 2018 Oct 5 IMPORTANCE: Autoimmune thyroid disease ([AITD] including hypothyroidism and hyperthyroidism) is the most common organ-specific autoimmune disorder and is more prevalent among patients with rheumatoid arthritis (RA). Real-world studies on when and how this increased risk of AITD develops, in association with the time before or after the onset of RA, are lacking. OBJECTIVE: To estimate the risk of thyroxine-treated AITD among patients with RA at different time points before and after the diagnosis of RA. DESIGN, SETTING, AND PARTICIPANTS: A nationwide register-based case-control and cohort study was conducted between January 1, 2006, and June 30, 2013, with a maximum follow-up time of 7 years before and 8 years after diagnosis of RA. The study used the Swedish Rheumatology Quality Register and linkage to other nationwide registers to identify 8090 adults with new-onset RA and a random population-based sample of 80 782 referents matched by age, sex, and residential area. Statistical analysis was performed from July 1, 2015, to June 30, 2017. EXPOSURES: Presence of AITD in the participants in the case-control design and RA in the participants in the cohort design. MAIN OUTCOMES AND MEASURES: Prevalence and relative risk of incident AITD before (odds ratios) and after (hazard ratios) diagnosis of RA compared with the population as reference. RESULTS: There were 8090 patients with RA (5529 women and 2561 men; mean [SD] age, 58.3 [15.2] years) and 80 782 population-based participants as reference who were identified. By the time of diagnosis of RA, the prevalence of AITD was 10.3% among the patients with RA (n = 832) vs 7.1% among the controls (5725 of 80 350) (odds ratio, 1.5; 95% CI, 1.4-1.7). This increased risk of AITD developed during the 5 years (range, 2-5 years) before diagnosis of RA (odds ratio, 1.5; 95% CI, 1.2-1.8) and peaked by the time of diagnosis of RA (range, 0-3 months before diagnosis of RA) (odds ratio, 5.3; 95% CI, 3.7-7.6). From diagnosis of RA and onward, the risk of developing AITD decreased (range, 2-5 years after diagnosis of RA) (hazard ratio, 0.7; 95% CI, 0.5-1.0). CONCLUSIONS AND RELEVANCE: Compared with the general population, Swedish patients with RA appear to have a higher prevalence of thyroxine-treated AITD at diagnosis of RA and an increased incidence of AITD during the 5-year period before diagnosis of RA. After diagnosis of RA, the risk of developing AITD is suggested to decrease below the expected rate. Besides temporal changes in diagnostic intensity, this pattern of risk raises the question whether AITD may influence the pathogenesis of RA (or vice versa) and, conversely, the question whether antirheumatic therapies may prevent AITD.
29780157 Targeting Acquired Hemophilia A with Rheumatoid Arthritis by a Rituximab Shot: A Case Repo 2018 May 21 BACKGROUND Acquired hemophilia A (AH) is a rare hemorrhagic diathesis, characterized by the presence of autoantibodies directed against the pro-coagulant activity of factor VIII. It is associated with rheumatoid arthritis (RA) in 4% to 8% of cases and its prognosis remains severe. CASE REPORT A 66-year-old patient has been followed up for 20 years for deforming and severe RA, which was in low-disease activity. However, the patient presented a polyarticular flare involving the metacarpophalangeal and the proximal interphalangeal joints, the left elbow, and the right knee, which was warm and swollen. Articular puncture of this knee yielded a hematic fluid that did not coagulate. Its cytological analysis showed significant presence of red blood cells, which were also abundantly present in the other cell lines. Activated partial thromboplastin time was lengthened and not corrected by the addition of control plasma. Prothrombin time (Quick's test), fibrinogen level, and vitamin K-dependent factors were without abnormalities. In contrast, factor VIII was collapsed at 7% and the anti-factor VIII antibody was positive. The diagnosis of AH with anti-factor VIII inhibitor was thus retained. With regard to RA, the Disease Activity Score was 6.32 and exhibited a very active RA. Rituximab with methotrexate was begun and the evolution was favorable. After 6 months, the reappearance of the anti-factor VIII inhibitor was found, thus justifying a second cycle of rituximab. CONCLUSIONS AH is not exceptional in RA. Rituximab remains a relevant alternative for managing simultaneous AH with inhibitor and RA.
29205926 A retrospective review of the persistence on bDMARDs prescribed for the treatment of rheum 2018 Aug AIM: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. METHOD: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-α (anti-TNFα) agents were combined as they were equivalent. RESULTS: Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. CONCLUSIONS: Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.
29452423 Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in 2018 May 1 OBJECTIVES: RA is an articular chronic inflammatory disease that in a subgroup of patients can also present with extra-articular manifestations (EAMs). Despite intense investigation on this topic, reliable biomarkers for EAMs are lacking. In recent years several ACPAs, including those targeting anti-citrullinated alpha enolase peptide-1 (anti-CEP-1), have been identified in patients with RA. Data about the ability of anti-CEP-1 to predict the development of erosive disease are confliciting and no evidence concerning their possible association with EAMs in RA is currently available. The aim of this study was to investigate the prevalence and significance of anti-CEP-1 with regard to the association with erosive disease and EAMs in a large cohort of patients with RA. METHODS: Anti-CCP and anti-CEP-1 antibodies have been assessed on serum samples of RA patients, healthy donors and patients with SpA using commercially available ELISA kits. RESULTS: Anti-CEP-1 antibodies are detectable in over 40% of RA patients and are associated with erosive RA and with RA-associated interstitial lung disease (ILD). CONCLUSION: Anti-CEP-1 antibodies may represent a useful biomarker for RA-associated ILD and erosive disease to be employed in clinical practice.
29315512 Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells. 2018 Jul Acute inflammation is a complex and tightly regulated homeostatic process that includes leucocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as rheumatoid arthritis (RA), it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells, including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets.
30475847 eDRAM: Effective early disease risk assessment with matrix factorization on a large-scale 2018 Recently, a number of analytical approaches for probing medical databases have been developed to assist in disease risk assessment and to determine the association of a clinical condition with others, so that better and intelligent healthcare can be provided. The early assessment of disease risk is an emerging topic in medical informatics. If diseases are detected at an early stage, prognosis can be improved and medical resources can be used more efficiently. For example, if rheumatoid arthritis (RA) is detected at an early stage, appropriate medications can be used to prevent bone deterioration. In early disease risk assessment, finding important risk factors from large-scale medical databases and performing individual disease risk assessment have been challenging tasks. A number of recent studies have considered risk factor analysis approaches, such as association rule mining, sequential rule mining, regression, and expert advice. In this study, to improve disease risk assessment, machine learning and matrix factorization techniques were integrated to discover important and implicit risk factors. A novel framework is proposed that can effectively assess early disease risks, and RA is used as a case study. This framework comprises three main stages: data preprocessing, risk factor optimization, and early disease risk assessment. This is the first study integrating matrix factorization and machine learning for disease risk assessment that is applied to a nation-wide and longitudinal medical diagnostic database. In the experimental evaluations, a cohort established from a large-scale medical database was used that included 1007 RA-diagnosed patients and 921,192 control patients examined over a nine-year follow-up period (2000-2008). The evaluation results demonstrate that the proposed approach is more efficient and stable for disease risk assessment than state-of-the-art methods.
30278237 Disease-related outcomes influence prevalence of falls in people with rheumatoid arthritis 2019 Mar BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of falls, with potential adverse outcomes. There is a considerable variation across studies regarding the prevalence of falls and its correlation with clinical data, disease-related outcomes and physical performance tests. OBJECTIVE: The aim of this study was to evaluate the prevalence of falls and its association with clinical data, disease-related outcomes and physical performance tests. METHODS: In this cross-sectional study, 113 RA patients were divided into 3 groups - "non-fallers", "sporadic fallers" and "recurrent fallers" - and compared in terms of clinical data, Clinical Disease Activity Index (CDAI), lower-limb tender and swollen joint count, disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), Foot Function Index (FFI), Berg Balance Scale (BBS), Timed-up-and-go Test (TUG) and 5-Time Sit Down-To-Stand Up Test (SST5). Logistic regression analysis was performed to analyze the associations between the studied variables and the occurrence of falls, estimating odds ratios (ORs). We also analyzed the correlation between disease outcome measures (HAQ-DI and CDAI) and physical tests (BBS, TUG, SST5). RESULTS: Falls and fear of falling were reported by 59 (52.21%) and 71 (64.5%) patients, respectively. Significant associations were found between "recurrent fallers" and vertigo (OR=3.42; P=0.03), fear of falling (OR=3.44; P=0.01), low income (OR=2.02; P=0.04), CDAI (OR=1.08; P<0.01), HAQ-DI (OR=3.66; P<0.01), Lower-limb HAQ (OR=3.48; P<0.01), FFI-pain (OR=1.24; P=0.03), FFI-total (OR=1.23; P=0.04), lower-limb tender joint count (OR=1.22; P<0.01), BBS score (OR=1.14; P<0.01), TUG score (OR=1.13; P=0.03) and SST5 score (OR=1.06; P=0.02). On multivariate analysis, CDAI was the only significant predictor of recurrent falls (OR=1.08; P<0.01). Physical performance test scores (BBS, TUG, SST5) were correlated with the CDAI and HAQ-DI. CONCLUSION: The prevalence of falls in RA is high, most influenced by disease-related outcomes and linked to worse performance on physical tests (BBS, TUG and SST5).
29667557 Modification of Sexual Hormones in Rheumatoid Arthritis Patients by M2000 (β-D-mannuronic 2018 BACKGROUND: Based on in-vitro, in-vivo and human studies, the β-D-mannuronic acid (M2000) has been introduced as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive properties. OBJECTIVE: This study aimed to evaluate the efficacy of this drug on serum level of sex hormones (Estradiol, Progesterone, and DHEAS) in rheumatoid arthritis (RA) patients. METHODS: The present research was performed on 10 RA patients who had an inadequate response to conventional treatments (clinical trial identifier: IRCT2014011213739N2). During this trial, the patients were permitted to continue the conventional therapy along with adding M2000 orally at a dose of 500 mg twice daily for 12 weeks. Serum samples were collected in a normal group, patient group (at baseline) and treatment group (after 12 weeks). The samples were tested for evaluating the serum level of Estradiol, Progesterone, and DHEAS using chemiluminescent microparticle immunoassay. RESULTS: Data showed that the serum level of estradiol was reduced (both in men and women) during the treatment with M2000 (after 12 weeks), but there was no significant difference in the non-treated group with M2000 (p > 0.05). In addition, the serum level of progesterone and DHEAS significantly increased following the 12-week administration of M2000 in both male and female patients, compared to the non-treated group with M2000 (p < 0.001, p < 0.05, p < 0.05, p < 0.01, respectively). CONCLUSION: The present research showed that the sex hormones might be modified by M2000 therapy in RA patients by increasing the serum level of progesterone and DHEAS compared to healthy individuals.
29873569 The role of self-efficacy in pain intensity, function, psychological factors, health behav 2020 Jan Objective: The aim of this study was to systematically review and critically appraise the role of self-efficacy in pain intensity, function, psychological factors, health behaviors, and quality of life in people with rheumatoid arthritis, based on the analyses of longitudinal studies. Methods: An electronic search of PubMed, AMED, CINAHL, PsycINFO, and PubPsych was carried out from inception to July 2017. Study selection was based on longitudinal studies which have explored the role of self-efficacy in rheumatoid arthritis. The Newcastle-Ottawa Scale adapted version was used to evaluate the risk of bias, whereas the Grading of Recommendations Assessment, Development and Evaluation evaluated the quality of the evidence per outcome. Results: A total of 11 articles met the inclusion criteria. Our results suggest an association between higher self-efficacy and greater goal achievement, positive affect, acceptance of illness, problem-solving coping, physical function, physical activity participation, and quality of life. Inversely, there was also an association between higher self-efficacy and lower pain intensity, depressive symptoms, and anxiety. Conclusions: The findings of this systematic review suggest that self-efficacy might have a positive effect on the prognosis of this condition, although further longitudinal studies are needed.
30130534 Association of serum lipids with autoantibodies and inflammatory markers in rheumatoid art 2018 Nov BACKGROUND: We studied the relationship between serum lipids and autoantibodies and inflammatory markers in rheumatoid arthritis (RA) patients to explore the effect of serum lipids on the diagnosis and judgment of disease activity in RA patients. METHODS: Serum lipids including TCHO, TG, HDLC and LDLC and anti-CCP, RF, CRP, ESR of RA patients from May 2013 to August 2017 were retrospectively analyzed in the First Affiliated Hospital of Fujian Medical University. RESULTS: With the dilution factor increased, the concentrations of serum lipids and anti-CCP, CRP and RF showed the same downward trend, indicating that the detection methods of the above indicators were reasonable and would not be affected by hyperlipidemia. CRP and ESR levels were negatively correlated with HDLC concentration in male and female RA patients. However, the concentration of anti-CCP and RF were closely related to TG. In all the RA patients and female RA patients, the RF level was negatively correlated with the TG concentration. Moreover, with the TG concentration increased, the proportion of patients with high concentrations of anti-CCP levels decreased. In addition, in male RA patients, anti-CCP and ESR concentration increased with the increase of LDLC. CONCLUSION: The concentrations of HDLC, TG and LDLC were associated with the concentration of anti-CCP, RF, CRP and ESR in RA patients. Therefore, clinical diagnosis of RA and determination of disease activity should consider the impact of the concentration of serum lipids in order to make a reasonable judgment on the diagnosis of the disease.
29306884 Retrospective cohort study on risk of hearing loss in patients with rheumatoid arthritis u 2018 Jan 5 OBJECTIVES: Population studies on hearing loss (HL) associated with rheumatoid arthritis (RA) are lacking. This study investigated the risk of developing HL in patients with RA using a nationwide population cohort. SETTING: The population-based insurance claims data in the Taiwan National Health Insurance Research Database. DESIGN: Retrospective cohort study followed up RA cohort and control cohort without RA frequency matched by sex, age and diagnosis year. STUDY POPULATION: 18 267 patients with RA newly diagnosed in 2000-2006 and 73 068 controls without RA. MAIN OUTCOMES: Incidences of HL by the end of 2011 and the RA cohort to non-RA cohort HRs after adjusting for sex, age and comorbidities. RESULTS: The HL incidence was higher in the RA cohort than in the non-RA cohort (3.08 vs 1.62 per 1000 person-years), with an adjusted HR (aHR) of 1.91 (95% CI 1.70 to 2.14) for the RA cohort relative to the non-RA cohort after controlling for age, sex and comorbidities. Men and the elderly are at a higher risk. Cardiovascular comorbidities were associated with a further increased HL risk for patients with RA. Medications were associated with reduced HL incidence; patients with RA who used non-steroidal anti-inflammatory drugs (NSAIDs) had an aHR of 0.12 (95% CI 0.07 to 0.20), compared with non-users. CONCLUSIONS: This study demonstrates that patients with RA are at an increased risk of developing HL. Findings highlight the need of disease-modifying treatment and scheduled auditory examinations for HL prevention and early detection for patients with RA.
29359231 Temporal trends and regional disparity in rheumatoid arthritis and gout hospitalizations i 2018 Mar Hospitalization is an important component of rheumatoid arthritis (RA) and gout economic burden. This study aimed to assess temporal trends and regional disparities in RA and gout hospitalizations among people aged ≥ 20 years in Sweden during 1998-2015. Data on hospital admissions with a principal diagnosis of RA or gout were collected from the National Patient Register. Age-standardized hospitalization rates (ASHRs) were calculated by means of direct standardization. The absolute and relative regional disparities were assessed. The temporal trends in ASHR and proportion of RA and gout hospitalizations from all and musculoskeletal disorders hospitalizations were analyzed using joinpoint regression. Between 1998-2000 and 2013-2015, the ASHR for RA declined by 78.9% from 109.9 to 23.2 per 100,000 Swedish adults, while it almost doubled for gout (from 10.5 to 20.8 per 100,000 Swedish adults). While in 1998-2000, RA hospitalizations were 10.3 times more frequent than gout (0.54 vs 0.05% of all hospitalizations), this ratio declined to 1.1 in 2013-2015 (0.13 vs 0.11% of all hospitalizations). The joinpoint regression revealed that, on average, the ASHR for RA declined by 10.2% (95% CI: 9.3-11.1) per year whereas for gout, it rose by 4.3% (3.2-5.4) per year during 1998-2015. While the relative regional disparities were stable, the absolute regional disparity declined for RA and increased for gout over the study period. While substantial decline in RA hospitalization is encouraging, the substantial rise in gout hospitalization is of concern, reflecting potential increase in prevalence of gout and suboptimal management of the disease.
29794789 The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin 2018 May To investigate the impact of comorbid diseases on rheumatoid arthritis (RA) outcome.All patients diagnosed with RA since 2006, who were registered in our local Danbio registry, were included in this cohort study. Patients' demographics, serology results, and Disease Activity Score in 28 joints-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months of treatment initiation were collected. Patients' electronic hospital records were evaluated for a positive history of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency, and the presence of other diagnosed autoimmune diseases.1035 RA patients were included. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid diseases and female gender (P < .001); DM and greater age (P < .001); primary hyperparathyroidism and longer disease duration (P = .002); other diagnosed autoimmune diseases and antinuclear antibody positivity (P < .001). RA patients with thyroid diseases (P = .001) and other comorbid autoimmune diseases (P < .001) had significantly poorer initial response to the RA treatment compared to patients with isolated RA.Univariate analyses revealed that age, the presence of thyroid diseases, the presence of other diagnosed autoimmune diseases and DAS28-CRP at the time of diagnosis were significantly associated with ΔDAS28-CRP. Additionally, multivariate analysis demonstrated that ΔDAS28-CRP deterioration was significantly correlated to the presence of thyroid diseases (unstandardized regression coefficient (standard error); -0.188 (0.088), P = .030) and the presence of other diagnosed autoimmune diseases (-0.537 (0.208), P = .010).RA patients are at increased risk of specific comorbidities with possible impact on the treatment outcome. To improve this situation, periodic assessment of comorbidities should be considered.
29802482 Systemic sclerosis-rheumatoid arthritis overlap syndrome complicated with Sweet's syndrome 2018 Aug Herein, we report a case of a 34-year-old woman with systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome (OS) complicated with Sweet's syndrome. OS has been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTD) occurring at the same or at different times in the same patient. The CTD include RA, SSc, systemic lupus erythematosus (SLE), polymyositis, and dermatomyositis. Sweet's syndrome also known as acute febrile neutrophilic dermatosis was first described by Robert Sweet in 1964. Sweet's syndrome is characterized by fever, neutrophilia, erythematous skin lesions, and a diffuse dermal infiltrate of mature neutrophils. There are sets of associations that we will discuss in this article between OS and Sweet's syndrome.
29750836 Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arth 2018 Sep Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm(2) , and 0.48 mm(3) versus 1.0, 0.69 mm(2) , and 0.23 mm(3) , respectively; all p < 0.01). Findings on CR and MRI were significantly associated with more and larger interruptions on HR-pQCT (prevalence ratios [PRs] ranging from 1.03 to 7.74; all p < 0.01) in all subjects, and were consistent in patients with RA alone. Having RA was significantly associated with more and larger interruptions on HR-pQCT (PRs, 2.33 to 5.39; all p < 0.01), also after adjustment for findings on CR or MRI. More and larger cortical interruptions were found in the finger joints of patients with RA versus healthy subjects, also after adjustment for findings on CR or MRI, implying that HR-pQCT imaging may be of value in addition to CR and MRI for the evaluation of structural damage in patients with RA. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
29471421 Class 3 semaphorins modulate the invasive capacity of rheumatoid arthritis fibroblast-like 2018 May 1 OBJECTIVE: Class 3 semaphorins regulate diverse cellular processes relevant to the pathology of RA, including immune modulation, angiogenesis, apoptosis and invasive cell migration. Therefore, we analysed the potential role of class 3 semaphorins in the pathology of RA. METHODS: Protein and mRNA expression in RA synovial tissue, SF and fibroblast-like synoviocytes (FLS) were determined by immunoblotting and quantitative PCR (qPCR). RA FLS migration and invasion were determined using wound closure and transwell invasion assays, respectively. PlexinA1, neuropilin-1 and neuropilin-2 expression was knocked down using small interfering RNA (siRNA). Activation of FLS intracellular signalling pathways was assessed by immunoblotting. RESULTS: mRNA expression of semaphorins (Sema)3B, Sema3C, Sema3F and Sema3G was significantly lower in the synovial tissue of early arthritis patients at baseline who developed persistent disease compared with patients with self-limiting disease after 2 years follow-up. Sema3B and Sema3F expression was significantly lower in arthritis patients fulfilling classification criteria for RA compared with those who did not. FLS expression of Sema3A was induced after stimulation with TNF, IL-1β or lipopolysaccharides (LPS), while Sema3B and Sema3F expression was downregulated. Exogenously applied Sema3A induced the migration and invasive capacity of FLS, while stimulation with Sema3B or Sema3F reduced spontaneous FLS migration, and platelet-derived growth factor induced cell invasion, effects associated with differential regulation of MMP expression and mediated by the PlexinA1 and neuropilin-1 and -2 receptors. CONCLUSION: Our data suggest that modulation of class 3 semaphorin signaling could be a novel therapeutic strategy for modulating the invasive behaviour of FLS in RA.
29671942 Comparative efficacy and safety of biosimilar-infliximab and originator-infliximab in comb 2018 May OBJECTIVE: We aimed to assess the relative efficacy and safety of biosimilar-infliximab and originator-infliximab in combination with methotrexate (MTX) compared to placebo plus MTX in active rheumatoid arthritis (RA). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of biosimilar + MTX and infliximab + MTX and placebo + MTX (MTX group) in patients with active RA despite treatment with MTX. RESULTS: Seven RCts involving 2606 patients met the inclusion criteria. The American College of Rheumatology (ACR)20 response rate was significantly higher in the biosimilar + MTX group than in the MTX group (odds ratio [OR] 3.31, 95% credible interval [CrI] 1.74-6.06). Similarly, the ACR20 response rate was significantly higher in the infliximab + MTX group than in the MTX group (OR 3.15, 95% CrI 1.99-4.70). There was no difference in the ACR20 response rate between the biosimilar+ MTX and infliximab + MTX groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that treatment with biosimilar + MTX had the highest probability of achieving the ACR20 response rate (SUCRA = 0.7964), followed by infliximab + MTX (SUCRA = 0.7018) and MTX alone (SUCRA = 0.0018). The ACR50 and ACR70 response rates showed a similar distribution pattern to the ACR20 response rate. By contrast, the safety based on the number of serious adverse events (SAEs) did not differ significantly among the three interventions. CONCLUSIONS: Biosimilar- and originator-infliximab, in combination with MTX, represent effective interventions for active RA, with a low risk of SAEs. No significant difference between biosimilar- and originator-infliximab was found in terms of efficacy and safety.
30535993 Risk factors for progression and prognosis of rheumatoid arthritis-associated interstitial 2019 Apr BACKGROUND: Factors associated with progression and survivals in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have not been described in a large center China cohort. METHODS: Seven-hundred and ninety-one consecutive RA patients who completed lung HRCT were considered as potential participants in this retrospective cohort study. Determinants of ILD progression were identified through multivariable logistic analysis. Cox hazards analysis was used to determine significant variables associated with survival. RESULTS: Of 307 patients diagnosed with RA-ILD, 266 were finally included. The 3-year survival rate of RA-ILD patients was 81.24%, and the 5-year survival rate was 69.71%. A total of 82 deaths occurred during follow-up, of which 56 died of respiratory failure due to ILD progression and/or pneumonia while 14 with malignancies (8 with lung cancer). Logistic regression analysis showed that anti-CCP antibody high titer positive (OR: 4.03, 95% CI: 1.04-15.69) and DLCO% < 45% (OR: 8.31, 95% CI: 2.17-31.75) were independent risk factors for the ILD progression. Cox hazards analysis revealed that advanced age (> 60 years old) of RA-ILD diagnosis (HR: 2.32, 95% CI: 1.27-4.25) and extensive lung involvement on HRCT (HR: 2.19, 95% CI: 1.24-3.87) were associated with worse survival. Treatment with cyclophosphamide (HR: 0.43, 95% CI: 0.26-0.69) was associated with better survival. CONCLUSIONS: In RA-ILD patients, anti-CCP antibody high titer positive and DLCO% < 45% are risk factors for ILD progression. Advanced age and extensive lung involvement on HRCT, rather than the baseline UIP pattern, independently predict mortality after controlling for potentially influential variables. Furthermore, cyclophosphamide treatment helps to improve the prognosis in real-world experience.