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ID PMID Title PublicationDate abstract
24989966 Influence of angulation on metacarpal bone mineral density measurements using digital X-ra 2015 May OBJECTIVE: Digital X-ray radiogrammetry (DXR) is a computer-assisted technique used to quantify cortical bone density of the metacarpals. The influence of metacarpal bone rotation and type of cast material on bone mineral density (BMD) measurements using the DXR technique was tested. METHODS: The bone mineral density of the hand was measured by DXR, and rotation error (DXR-RE) as coefficients of variation were calculated, to verify reliability and reproducibility of this radiogeometric technique to assess in particular minor disease-related changes in the metacarpal bone mass. The reproducibility of the DXR measurements was also investigated using different cast materials (mull, elastic, and plastic). RESULTS: There were no significant changes in absolute values of DXR-BMD observed between 0 to [Formula: see text] angulation. The relative DXR-RE ranged between 0 % (degree 1) and 0.70 % (degrees 15 and 19) for DXR-BMD. Regarding the different cast materials, DXR-BMD revealed a coefficient of variation with 0.41 % (mull cast) and 0.21 % (elastic cast). For the plastic cast, the DXR technique was not able to perform an analysis of DXR-BMD. CONCLUSION: The study revealed no significant influence of metacarpal rotation on the measurements of metacarpal bone mineral density as estimated by DXR. DXR measurements are not optimal when cast material is used. DXR can accurately quantify periarticular cortical bone mass. This is significant especially for rheumatoid arthritis and related conditions where X-ray imaging of arthritic hands with varying degrees of deformity is performed.
26391694 Self-assessment of Rheumatoid Arthritis Disease Activity Using a Smartphone Application. D 2016 INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". BACKGROUND: Rheumatoid arthritis (RA) is a progressive inflammatory disease that causes damage to multiple joints, decline in functional status, and premature mortality. Thus, effective and frequent objective assessments are necessary. Then, we developed a self-assessment system for RA patients based on a smartphone application. OBJECTIVE: The purpose of this study was to investigate the feasibility of a self-assessment system for RA patients using a smartphone application. METHODS: We measured daily disease activity in nine RA patients who used the smartphone application for a period of three months. A disease activity score (DAS28) predictive model was used and feedback comments relating to disease activity were shown to patients via the smartphone application each day. To assess participants' RA disease activity, the DAS28 based on the C-reactive protein level was measured by a rheumatologist during monthly clinical visits. RESULTS: The disease activity measured by the application correlated well with the patients' actual disease activity during the 3-month period, as assessed by clinical examination. Furthermore, most participants gave favourable responses to a questionnaire administered at the end of the 3-month period containing questions relating to the ease of use and usefulness of the system. CONCLUSIONS: The results of this feasibility study indicated that the DAS28 predictive model can longitudinally predict DAS28 and may be an acceptable and useful tool for assessment of RA disease activity for both patients and healthcare providers.
26097183 A BAFF receptor His159Tyr mutation in Sjögren's syndrome-related lymphoproliferation. 2015 Oct OBJECTIVE: To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF-R) in patients with Sjögren's syndrome (SS). METHODS: The BAFF-R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)-based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS-lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real-time PCR and Western blotting were performed for the quantification of both NF-κB1 and NF-κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS-lymphoma carrying the mutation (SS-lymphoma-BAFF-RHis159Tyr -derived B cells) compared to B cells from patients with SS-lymphoma who were not carriers of the mutation and healthy controls. RESULTS: Both the SS-lymphoma and SS-nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF-R mutation compared to healthy controls (8.6% of SS-lymphoma patients and 6.2% of SS-nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF-R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS-related MALT lymphoma in the younger age at onset (age <40 years) group in the presence of the BAFF-R mutation was 6.1 (95% confidence interval 2.0-18.7) (P < 0.01). Expression of NF-κB at both the mRNA and protein level was up-regulated in SS-lymphoma-BAFF-RHis159Tyr -derived B cells. CONCLUSION: This study identifies an increased prevalence of the BAFF-R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF-RHis159Tyr -mediated activation of the alternate NF-κB pathway might contribute to the pathogenesis of SS-related lymphoproliferative disease.
27681594 Bone-protective Functions of Netrin 1 Protein. 2016 Nov 11 Netrin 1 was initially identified as an axon guidance factor, and recent studies indicate that it inhibits chemokine-directed monocyte migration. Despite its importance as a neuroimmune guidance cue, the role of netrin 1 in osteoclasts is largely unknown. Here we detected high netrin 1 levels in the synovial fluid of rheumatoid arthritis patients. Netrin 1 is potently expressed in osteoblasts and synovial fibroblasts, and IL-17 robustly enhances netrin 1 expression in these cells. The binding of netrin 1 to its receptor UNC5b on osteoclasts resulted in activation of SHP1, which inhibited VAV3 phosphorylation and RAC1 activation. This significantly impaired the actin polymerization and fusion, but not the differentiation of osteoclast. Strikingly, netrin 1 treatment prevented bone erosion in an autoimmune arthritis model and age-related bone destruction. Therefore, the netrin 1-UNC5b axis is a novel therapeutic target for bone-destructive diseases.
26879354 The Rate of Adherence to Antiarthritis Medications and Associated Factors among Patients w 2016 Mar OBJECTIVE: Reported adherence in rheumatoid arthritis (RA) varies widely (10.5-98.5%). Variability may result in part from different methods used to measure adherence. Our aims were to quantify adherence to antiarthritis medications for each method and to identify variability and associated factors. METHODS: The systematic literature review examined PubMed, the Cochrane central database, and article reference lists from 1970 to November 2014. Papers with medication adherence data (disease-modifying antirheumatic drugs, steroids, and nonsteroidal antiinflammatory drugs) in adult patients with RA or data on associated factors were included. Adherence rate was recorded for each method. Random-effect metaanalysis estimated adherence for different evaluation methods. RESULTS: Adherence rate was 66% (95% CI 0.58-0.75). There were no differences in adherence among different measurement methods (interview, questionnaires, etc.). Regression analysis showed that adherence decreases during followup. Among 100 possible factors potentially effecting adherence, 7 adherence-associated factors were found in at least 2 different studies. These were the use of infliximab compared with etanercept or methotrexate (MTX), use of MTX compared to sulfasalazine or to etanercept, belief in the necessity of the medications, older age, and white race. CONCLUSION: Overall adherence rate was 66%. We suggest that readers appraise adherence studies according to the medications evaluated, the validity of the method, and the scales and cutpoints.
26028353 Update on the role of Interleukin 17 in rheumatologic autoimmune diseases. 2015 Oct Interleukin 17 is a proinflammatory cytokine produced by CD4+ T cells when in the presence of a distinct set of cytokines and other cells. Preclinical and clinical studies have assigned a role to IL-17 in tissue inflammation and damage in patients with rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis and systemic lupus erythematosus. Antibodies blocking the action of IL-17 have already been approved to treat patients with psoriasis and it is expected that they may also benefit patients with other rheumatic diseases.
27775453 The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs 2017 May OBJECTIVES: To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). METHOD: Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. RESULTS: No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. CONCLUSIONS: Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.
25543267 Consensus statement on a framework for the management of comorbidity and extra-articular m 2015 Mar The objective of the study was to develop evidence-based and practical recommendations for the detection and management of comorbidity in patients with rheumatoid arthritis (RA) in daily practice. We used a modified RAND/UCLA methodology and systematic review (SR). The process map and specific recommendations, based on the SR, were established in discussion groups. A two round Delphi survey permitted (1) to prioritize the recommendations, (2) to refine them, and (3) to evaluate their agreement by a large group of users. The recommendations cover: (1) which comorbidities should be investigated in clinical practice at the first and following visits (including treatments, risk factors and patient's features that might interfere with RA management); (2) how and when should comorbidities and risk factors be investigated; (3) how to manage specific comorbidities, related or non-related to RA, including major adverse events of RA treatment, and to promote health (general and musculoskeletal health); and (4) specific recommendations to assure an integral care approach for RA patients with any comorbidity, such as health care models for chronic inflammatory patients, early arthritis units, relationships with primary care, specialized nursing care, and self-management. These recommendations are intended to guide rheumatologists, patients, and other stakeholders, on the early diagnosis and management of comorbidity in RA, in order to improve disease outcomes.
25617221 Surface replacement arthroplasty of the proximal interphalangeal joint using the SR PIP im 2015 Mar PURPOSE: To evaluate the long-term results of proximal interphalangeal (PIP) joint surface replacement arthroplasty for arthritis using the SR PIP implant (Small Bone Innovations, New York, NY). METHODS: This is a long-term retrospective analysis of results in 39 of 43 joints first reported in 2008. Subjective results were based upon a mailed questionnaire. Active range of motion was measured by a certified hand therapist, and x-rays were obtained to analyze changes occurring since the first study. RESULTS: The average follow-up time was 9.3 years. The average active PIP joint arc of motion in the present cohort of patients went from 64° at the first report (2008) to 56° at this time. Radiographic comparisons revealed no major changes since the first study. Ten of 11 revisions were done for pain due to loosening and were performed at an average of 20 months after the primary procedure. No further revisions were necessary in the interim. Overall, subjective measures of satisfaction and symptomatic and functional improvement remained unchanged. CONCLUSIONS: Surface replacement arthroplasty using the SR PIP implant continues to be an option for patients with osteoarthritis of the PIP joint. Long-term subjective and objective outcomes are comparable to those reported using other implants. This and other studies suggest that this procedure is not appropriate for most rheumatoid joints. In the interim between studies, we saw a reduction in the average PIP joint arc of motion, although this change did not reach statistical significance. Our original revision incidence of 26% has not changed. Subjective evaluation and radiologic findings did not change between studies. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
27184046 A randomized, controlled trial of efficacy and safety of Anbainuo, a bio-similar etanercep 2016 Sep The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group-significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. -3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.
27662596 Immunosuppressive effect of ASP2408, a novel CD86-selective variant of CTLA4-Ig, in rats a 2016 Nov The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods. Here we evaluated the effect of ASP2408 in vitro using cynomolgus monkey and rat T cell proliferation assays and in vivo using cynomolgus monkey tetanus toxoid (TTx) immunization and a rat rheumatoid arthritis model. ASP2408 was 290-fold and 21-fold more potent in suppressing in vitro monkey T cell proliferation than abatacept and belatacept, respectively. ASP2408 inhibited anti-TTx immunological reactions in cynomolgus monkey at a 10-fold lower dose level than belatacept, through complete CD86 and partial CD80 receptor occupancies, and also suppressed inflammation in the rat collagen-induced arthritis model. Overall, improved immunosuppressive potency of ASP2408 relative to abatacept and belatacept correlated well with improved CD86 binding affinity. These results may support the advantage of preferential enhancement of CD86 binding affinity to inhibit T cell-mediated immune response and improved dosing convenience in humans relative to abatacept or belatacept.
26864307 Patient rated outcomes study into the surgical interventions available for the rheumatoid 2016 Apr INTRODUCTION: A multitude of surgical interventions are recognised for the treatment of the rheumatoid hand and wrist, however there seems to be a distinct lack of patient rated outcome measures (PROMs) studies reporting on the efficacy of these procedures. The aim of this study was to assess the PROMs related to hand and wrist surgery in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: A single surgeon series identified 94 patients (133 hands) with RA who had undergone one of eight surgical procedures (Swanson's arthroplasty, finger joint or wrist arthrodesis, carpal tunnel decompression, posterior interosseous nerve denervation, RA nodule excision, synovectomy/tenosynovectomy and tendon repair/release) with a mean follow-up period of 3 years. The primary outcome measures were the same for all patients and comprised the validated modified score for the assessment and quantification of chronic rheumatoid affections of the hand (M-SACRAH) and a separate satisfaction questionnaire. RESULTS: Highly significant improvements in both function and pain scores are reported across the cohort as a whole following hand surgery, with this pattern replicated within all of the operative subgroups. In keeping with these favourable results very high levels of overall satisfaction were reported with 93 % of patients reporting themselves to be very or fairly satisfied with their procedure. CONCLUSIONS: Overall, patient reported outcomes in functional, stiffness and pain domains of the M-SACRAH questionnaire appear very favourable across the range of surgical procedures that can be performed in the rheumatoid hand. We believe this data supports the use of all the procedures explored, and will be helpful in patient guidance.
27886693 Gaps in Aging Research as it Applies to Rheumatologic Clinical Care. 2017 Feb The incidence and prevalence of rheumatologic conditions are increasing and the rheumatology workforce must be aware of aging-specific issues. This article reviews specific barriers to understanding the biology of aging and aging-related mechanisms that may underlie development of rheumatologic diseases in older adults. It summarizes gaps in the assessment, outcomes measurement, and treatment of these diseases in this unique population. It also highlights potential solutions to these barriers and suggests possible ways to bridge the gap, from a research and education standpoint, so that clinicians can be better prepared to effectively manage older adults with rheumatologic conditions.
27852376 [Rheumatoid arthritis involving tibialis posterior tendon: study on the early diagnostic v 2016 Nov 8 Objective: To explore the value of power Doppler ultrasonography (PDUS) in the early diagnosis of tibialis posterior tendon injury induced by rheumatoid arthritis (RA). Method: From January 2014 to December 2015, a total of 48 cases (60 feet) of RA tendinopathy group were selected as the research subjects from Guanghua Hospital; 12 cases(20 feet) of non-RA tendinopathy group and 10 cases (20 feet) of healthy volunteers were selected as control group.The blood flow signals of pannus were observed by PDUS to determine whether the tendon was injured or the degree of the injury. The following indexes were compared and analyzed by Chi-square testing: (1)positive rate of blood flow signal; (2)grade of blood flow signal; (3)spatial distribution of blood flow signal: diffusibility or local. Results: Of 70 cases(100 feet) in the study, the positive blood flow signals were only in the RA(88.3%) and non-RA group(40.0%) .Grade â…¢ in RA was 20.0%, while this was not observed in non-RA . Grade â…¡ in RA and non-RA was 36.7% and 10.0% , respectively. There were significant differences in the positive rate and grades between RA and non-RA group (P<0.01). The spatial distribution of blood flow signal in RA was significantly different from that in non-RA. In RA, they can be detected in the whole tendon.However, they were mainly distributed around the scaphoid in non-RA. In this study, three patients with grade â…¢were treated with surgery. The intraoperative findings were consistent with the preoperative ultrasound results. Conclusions: PDUS can be used to detect the neovascular formation of tendon synovitis. It can detect the early tendon injury before the appearance of foot deformity induced by RA, which can guide clinical early intervention treatment and prevent the occurrence of deformity and other serious consequences.
25732870 Gαq controls rheumatoid arthritis via regulation of Th17 differentiation. 2015 Aug Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq(-/-) mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq(-/-) mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.
27319613 Sleep disturbance in patients with rheumatoid arthritis is related to fatigue, disease act 2017 Mar OBJECTIVES: To explore factors related to sleep disturbance in patients with rheumatoid arthritis (RA). METHOD: Cross-sectional data from 986 patients in the Oslo RA Register (ORAR) collected in 2009 were included. Sleep problems were assessed by four measures: the Medical Outcomes Study (MOS) sleep disturbance scale, and the sleep components of the Rheumatoid Arthritis Impact of Disease (RAID) score, the Multi-Dimensional Health Assessment Questionnaire (MDHAQ), and the 15-dimensional quality of life questionnaire (15D). Patient-reported outcomes (PROs) were recorded using standard questionnaires for physical and mental function [the HAQ and the MOS 36-item Short-Form Health Survey (SF-36), disease activity (the RA Disease Activity Index, RADAI), utility (SF-6D), and visual analogue scales (VAS) for pain, fatigue, and disease activity]. Demographics including comorbidity were collected. Information on use of medication for RA and sleep disturbance was obtained using checklists. Multivariate analyses were used to identify factors independently associated with sleep problems by four different measures. RESULTS: The mean (standard deviation, SD) age of the patients was 59.4 (12.5) years, 76.9% were females, and the mean (SD) disease duration was 13.7 (10.7) years. The correlation between the various sleep measures was high (r(2) = 0.71-0.78). Sleep disturbance was moderately correlated to pain (r(2) = 0.41-0.61), fatigue (r(2) = 0.44-0.58), physical function (r(2) = 0.33-0.48), RADAI (r(2) = 0.42-0.55), and utility (r(2) = 0.49-0.61). RAID sleep demonstrated the highest correlation with other PROs. RADAI, fatigue, the mental component score of SF-36, physical function, body mass index (BMI), and use of Z-drugs/benzodiazepines were independently associated with two or more measures of sleep problems (all p < 0.001). CONCLUSIONS: Sleep disturbance measured by four different measures was independently related to other PROs including fatigue, pain, and disease activity in RA patients.
27032755 Value of body mass index in the diagnosis of obesity according to DEXA in well-controlled 2017 Jan BACKGROUND: Rheumatoid arthritis (RA) has an indirect effect on body composition. Body mass index (BMI) is not a valid predictor of body fat in RA patients. OBJECTIVE: To evaluate the accuracy of BMI in identifying obesity diagnosed according to dual energy X-ray absorptiometry (DXA) in well-controlled RA patients. METHODS: An observational, cross-sectional, descriptive, analytical study. We used 3 different cutoffs for obesity as determined by DXA: >35% total fat, >40% total fat, and >35% central fat mass (central obesity). RESULTS: One hundred one patients were included. We found that 35% total fat corresponded to a BMI of 24kg/m(2), with a sensitivity of 90% and specificity of 75% (area under the curve [AUC] 0.917); 40% total fat to a BMI of 25kg/m(2), with a sensitivity of 86% and specificity of 39% (AUC 0.822); and 35% central fat mass to a BMI of 22kg/m(2), with a sensitivity of 97% and specificity of 84% (AUC 0.951). CONCLUSION: Obesity according to DXA was underdiagnosed when the classic BMI cutoffs were used in well-controlled RA patients.
28002483 Physical Characteristics of a Citrullinated Pro-Filaggrin Epitope Recognized by Anti-Citru 2016 Rheumatoid arthritis (RA) is an autoimmune disease of complex etiology. A characteristic feature of a subset of RA is the presence of anti-citrullinated protein antibodies (ACPA), which correlate with a progressive disease course. In this study, we employed streptavidin capture enzyme-linked immunosorbent assay to analyze ACPA reactivity. Using the pro-filaggrin peptide HQCHQEST-Cit-GRSRGRCGRSGS, as template, we analyzed the reactivity of RA sera and healthy donor sera to various peptides in order to determine the physical characteristics of the citrullinated pro-filaggrin epitope and to examine whether biotin labelling influence antibody recognition. The full-length cyclic pro-filaggrin peptide and a linear form with a N-terminal biotin, was recognized to the same level, whereas, a notable difference in ACPA reactivity to the linear peptides with a C-terminal biotin was found, probably due to steric hindrance. Screening of linear and cyclic truncated peptides, revealed that small cyclic peptides containing 10-12 amino acids are favored over the linear. Moreover, the charged amino acids C-terminal to citrulline were found to be essential for antibody reactivity, most important was the charged amino acid in position 4 C-terminal to citrulline. Collectively, peptide structure, length, the presence of charged amino acids and biotin labelling markedly influence antibody reactivity. In relation to the clinical diagnostics of ACPA, these findings may reflect the differences in diagnostic assays used for detection of ACPA, which relates to differences in sensitivity and specificity dependent on the assay applied.
27641309 Comparative effectiveness of adalimumab and etanercept for rheumatoid arthritis in the Bra 2016 Nov AIM: Biological disease-modifying antirheumatic drugs (bDMARDs) are used to treat rheumatoid arthritis (RA) with adalimumab and etanercept the most used bDMARDs in Brazil. This open prospective cohort study evaluated their effectiveness and safety among RA patients in the Brazilian Public Health System given their costs. METHODS: The Clinical Disease Activity Index was primarily used to assess their effectiveness after 6 and 12 months of follow-up. The Health Assessment Questionnaire and EuroQol-5D were also used. RESULTS: A total of 266 RA patients started treatment with adalimumab or etanercept. Adalimumab was the most widely used bDMARD (70%). In total, 46% achieved remission or low-disease activity at 12 months with no difference in effectiveness between them (p = 0.306). bDMARDs were more effective in patients who had better functionality at treatment onset and had spent longer in education. CONCLUSION: This real-world study demonstrated that adalimumab and etanercept are equal alternatives for RA treatment and both were well tolerated.
26980577 Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature 2016 May OBJECTIVE: To evaluate the relative risk (RR) of pulmonary disease among patients with rheumatoid arthritis (RA) treated with leflunomide (LEF). METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to April 15, 2014. We included double-blind randomized controlled trials (RCT) of LEF versus placebo or active comparator agents in adults with RA. Studies with fewer than 50 subjects or shorter than 12 weeks were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. We compared RR differences using the Mantel-Haenszel random-effects method to assess total respiratory adverse events, infectious respiratory adverse events, noninfectious respiratory adverse events, interstitial lung disease, and death. RESULTS: Our literature search returned 5673 results. A total of 8 studies, 4 with placebo comparators, met our inclusion criteria. There were 708 respiratory adverse events documented in 4579 participants. Six cases of pneumonitis occurred, all in the comparator group. Four pulmonary deaths were reported, none in the LEF group. LEF was not associated with an increased risk of total adverse respiratory events (RR 0.99, 95% CI 0.56-1.78) or infectious respiratory adverse events (RR 1.02, 95% CI 0.58-1.82). LEF was associated with a decreased risk of noninfectious respiratory adverse events (RR 0.64, 95% CI 0.41-0.97). CONCLUSION: Our study found no evidence of increased respiratory adverse events in RCT of LEF treatment.