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ID PMID Title PublicationDate abstract
27564223 Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in 2017 Jan OBJECTIVE: To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease-modifying antirheumatic drug treatment. METHODS: A total of 2,701 patients were recruited over 25 years to 2 UK-based RA inception cohorts: the Early Rheumatoid Arthritis Study (9 centers; 1986-2001) and the Early Rheumatoid Arthritis Network (23 centers; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed-effects models, including random effects for recruitment center. RESULTS: Age at onset increased from 53.2 to 57.7 years in 1990 and 2010, respectively (2.6 months/year; 95% confidence interval [95% CI] 1.2, 4.1). Sex ratio, the proportion living in deprived areas, and smoking status were unchanged (P > 0.05) and there were no changes in the proportion seropositive or erosive at baseline (P > 0.05). After controlling for treatment at the time of assessment, erythrocyte sedimentation rate decreased and hemoglobin increased over time (P > 0.05); however, the Health Assessment Questionnaire (HAQ), the Disease Activity Score (DAS), the DAS in 28 joints, and joint counts were unchanged (P > 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions, including hypertension. There was a significant increase in body mass index (0.15 units/year; 95% CI 0.11, 0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. CONCLUSION: Age at onset and comorbidity burden, especially obesity, have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast, there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity, or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of comorbidity on outcomes.
29102157 The UltraSound-CLinical ARthritis Activity (US-CLARA) index: Properties of a new composite 2018 Apr OBJECTIVE: To assess validity, responsiveness and interpretability of the UltraSound-CLinical ARthritis Activity (US-CLARA) index in patients with rheumatoid arthritis (RA). METHODS: In this longitudinal study were involved RA patients starting treatment with abatacept. Subjects were followed along three visits in the first 6 months of therapy and underwent a comprehensive clinimetric evaluation. Validity was explored correlating the baseline scores and the cumulative inflammatory burden of the US-CLARA with the other composite indices applied. Sensitivity to change was assessed after 6 months of treatment in terms of internal and external responsiveness. Interpretability was defined in terms of determination of cutoffs against external criteria for remission (REM), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) of SDAI. RESULTS: One-hundred and thirty patients completed the study. VALIDITY: moderate correlations were observed between US-CLARA and both DAS28-CRP and DAS28-ESR. Higher correlations were also found between US-CLARA and both SDAI and CDAI scores. Responsiveness: internal responsiveness was wide, with SRM and ES ranging from 0.91 to 1.51. US-CLARA responsiveness was similar to that of DAS28, SDAI, or CDAI. Similarly, the area under ROC curve (AUC-ROC) of US-CLARA gives identical results. The AUC of cumulative inflammatory burden, calculated during the 6-months follow-up of all combinations were highly correlated (p < 0.0001). Interpretability: cutoff values for REM, US-CLARA <2.0; for LDA, 2.0 ≤US-CLARA <3; for MDA, 3 ≤US-CLARA ≤4.8; for HDA, US-CLARA >4.8. CONCLUSION: The US-CLARA is valid and sensitive tool to assess disease activity in RA.
29070455 [Efficacy of internalized RGD-modified echogenic liposomes in diagnosis and treatment in a 2017 Oct 20 OBJECTIVE: To prepare internalized RGD (iRGD) modified echogenic liposomes containing methotrexate (MTX) and indocyanine green (ICG) (iRGD MTX ICG ELIP) and evaluate its targeting efficiency and inhibitory effect combined with ultrasound on synovial cells. METHODS: iRGD MTX ICG ELIP was prepared by the thin film rehydration and freeze-lyophilization method and its general characteristics and acoustic responsiveness were assessed. The targeting effect of the prepared liposome was observed by assessing its cell uptake in vitro. In a mouse model of rheumatiod arthritis, the targeting effect of the prepared liposome was determined by detecting the fluorescence intensity of the drug in arthrosis. The inhibitory effect of iRGD MTX ICG ELIP combined with ultrasound on synovial MH7A cells in vitro were investigated using CCK8 test. RESULTS: The average diameter and zeta potential of iRGD MTX ICG ELIP was 134.4∓17.61 nm and 10.07∓4.28 mV, and the entrapment efficiency of MTX and ICG was (62.56∓0.77)% and (95.13∓0.82)%, respectively. With ultrasound exposure, the release of MTX and ICG from iRGD MTX ICG ELIP increased with the ultrasound intensity and with the exposure time. In HUVECs, the uptake efficiency of iRGD MTX ICG ELIP was 1.89 times higher than that of non targeted MTX ICG ELIP (P<0.05). In vivo imaging of mouse joint with rheumatiod arthritis showed that the fluorescence intensity of iRGD MTX ICG ELIP was significantly stronger than that of the non targeted liposome. CCK8 assay showed that iRGD MTX ICG ELIP combined with ultrasound resulted in a survival rate of MH7A cells of (32.49∓3.04)%, significantly lower than the rate of cells treated with iRGD MTX ICG ELIP but without ultrasound (P<0.05). CONCLUSIONS: iRGD MTX ICG ELIP has a suitable particle size and can effectively target HUVECs and the joints with rheumatiod arthritis. With a good drug entrapment efficiency and acoustic responsiveness, the drug loaded liposome shows enhanced inhibitory effect on MH7A cells combined with ultrasound in vitro, suggesting its potential in the treatment of rheumatoid arthritis.
27696766 Utilization of Care Outside the Veterans Affairs Health Care System by US Veterans With Rh 2017 Jun OBJECTIVE: Many veterans enrolled in Veterans Affairs (VA) health care systems also receive care through other health care systems. Both VA and non-VA health care use must therefore be considered when conducting research in this population. This study characterized dual-care utilization in veterans with rheumatoid arthritis (RA) and explored associations with RA disease activity. METHODS: Through a questionnaire mailed to RA patients at 3 VA sites, veterans reported medical services by non-VA primary care and subspecialty providers, comorbidities, non-VA medications, and hospitalizations. Disease Activity Score in 28 joints (DAS28) and Multidimensional Health Assessment Questionnaire (MD-HAQ) scores were recorded during VA clinic visits, and respondent groups were compared. RESULTS: Of the 510 participants surveyed, 318 (62%) responded. Respondents were older (ages 69 versus 66 years; P = 0.006), more likely nonsmokers (80% versus 67%; P = 0.001), and had lower disease activity (DAS28 3.3 versus 3.8; P < 0.001, MD-HAQ 0.8 versus 0.9; P = 0.01) than nonrespondents (n = 192 [38%]). The respondents with a non-VA provider (n = 130 [41%]) were older (71 versus 68 years; P = 0.001) and had more education (14 versus 13 years; P = 0.021) than nondual-care users. Only 6% of respondents reported having a non-VA rheumatologist, with 2% receiving a non-VA prescribed biologic agent or disease-modifying antirheumatic drug. CONCLUSION: In this study, VA beneficiaries with RA had lower dual-care utilization than previously reported for the general VA population, with few patients receiving dual rheumatology care or non-VA RA medications. This survey suggests that most US veterans with RA who access VA care use the VA as their primary source of arthritis care.
27696779 Standards of Comparison and Discordance in Rheumatoid Arthritis Global Assessments Between 2017 Aug OBJECTIVE: Patient-physician discordance in health status ratings may arise because patients use temporal comparisons (comparing their current status with their previous status), while clinicians use social comparisons (comparing this patient's status to that of other patients, or to the full range of disease severity possible) to guide their assessments. We compared discordance between patients with rheumatoid arthritis (RA) and clinicians, using either the conventional patient global assessment (PGA) or a rating scale with 5 anchors describing different health states. We hypothesized that discordance would be smaller with the rating scale because clinicians likely used similar social comparisons when making global assessments. METHODS: We prospectively studied 206 patients with active RA and assessed the PGA (range 0-100), rating scale (range 0-100), and evaluator global assessment (EGA; range 0-100) on each of 2 visits (total visits = 401). We compared the PGA/EGA discordance and the rating scale/EGA discordance at each visit. RESULTS: The mean ± SD PGA/EGA discordance was 8.5 ± 22.4, and the mean ± SD rating scale/EGA discordance was 2.3 ± 24.0. The intraclass correlation, measuring agreement, was higher between the rating scale and EGA than between the PGA and EGA (0.39 versus 0.31). Agreement was larger at low levels of RA activity on both pairs of measures. CONCLUSION: Discordance between patients' global assessments and evaluators' global assessments was smaller when patients used a social standard of comparison than when they marked the PGA, suggesting that differences in standards of comparison contribute to patient-clinician discordance when the PGA is used.
29221603 Emerging therapies for pre-RA. 2017 Feb The field of rheumatology has made major contributions to medicine through the identification of cellular and molecular targets and the development of therapies for the treatment of an impressive range of immune-mediated inflammatory diseases such as rheumatoid arthritis. In recent years, new milestones have been achieved. These include the recognition of an at-risk state, characterized by disease specific autoantibodies in serum and inflammatory joint pain, and the initiation of studies seeking to prevent high-risk individuals from progressing to a state of clinically apparent arthritis. Here, the current state of the art of rheumatoid arthritis prevention is described, highlighting the importance of risk stratification and reporting on a growing portfolio of therapeutic interventions targeting different stages of the preclinical syndrome.
28866909 The relationship between work, mental health, physical health, and fatigue in patients wit 2020 Apr To evaluate the relationship between work, mental health, physical health, and fatigue in patients with rheumatoid arthritis, the data of 282 participants were drawn from baseline. The results of structural equation modeling showed that among rheumatoid arthritis patients, those who were engaged in occupational activity had lower levels of fatigue compared to those who did not work and that this relationship was mediated by better mental health, not by physical health.
27699655 Serum level of neopterin is not a marker of disease activity in treated rheumatoid arthrit 2017 Sep Neopterin has been measured in many autoimmune diseases and was reported as a marker of cellular immunity activation in rheumatoid asthritis (RA). The aim of this work was to assess serum neopterin as a marker of disease activity in treated RA patients. We measured serum level of neopterin in 120 treated RA patients and 100 age- and sex-matched controls by high-performance liquid chromatography (HPLC) method, and disease activity score was calculated in all patients by DAS28-CRP score. Significantly higher levels of neopterin were observed in RA patients (11.46 ± 3.56 nmol/L) compared to healthy controls (4.74 ± 1.98 nmol/L), P < 0.0001. Significantly higher neopterin levels were observed among male RA patients [median (IQR), 13.44 (12.65-16.21)] than female RA patients [median (IQR), 11.86 (7.91-13.44)], P <0.0001. No significant correlations between neopterin and age, age of disease onset, disease duration, or any of the disease activity parameters were found. Moreover, no significant difference regarding neopterin levels in different disease activity phases was identified. Our results indicated that neopterin is a marker of RA but not a marker of disease activity in treated RA patients.
27145430 Drug breakthrough offers hope to arthritis sufferers: qualitative analysis of medical rese 2017 Apr BACKGROUND: Newspaper stories can impact behaviours, particularly in relation to research participation. It is therefore important to understand the narratives presented and ways in which these are received. Some work to date assumes journalism transmits existing medical knowledge to a passive audience. This study aimed to explore how newspaper articles present stories about medical research and how people interpret and use them. DESIGN: Qualitative research methods were employed to analyse two data sets: newspaper articles relating to 'rheumatoid arthritis' and 'research' from UK local and national news sources; and existing transcripts of interviews with patients with rheumatoid arthritis and their carers. RESULTS: Newspapers present a positive account of medical research, through a simple narrative with three essential components: an 'innovation' offers 'hope' in the context of 'burden'. Patients frequently feature as passive subjects without attributed opinions. Few articles include patients' experiences of research involvement. Patients with rheumatoid arthritis and their carers read articles about medical research critically, often with cynicism and drawing on other sources for interpretation. CONCLUSIONS: An understanding of the simple, positive narrative of medical research found in newspaper articles may enable researchers to gain mass media exposure for their work and challenge this typical style of reporting. The critical and cynical ways patients and carers read stories about medical research suggest that concerns about newspaper articles misinforming the public may be overstated, but any effect on research engagement is unknown. Newspaper articles rarely present patients' views or their experiences of research, and this can be conceptualized as 'depersonalization bias'.
28407099 Discontinuation of tofacitinib after achieving low disease activity in patients with rheum 2017 Aug 1 OBJECTIVE: To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). METHODS: RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. RESULTS: Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. CONCLUSION: It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib.
27696788 Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Allel 2017 Mar OBJECTIVE: Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single-nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. METHODS: Coronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect. RESULTS: Ninety-one CAD-related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD-related SNP genetic risk score. CONCLUSION: The increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population.
29079568 Comparative Risk of Cardiovascular Outcomes Between Topical and Oral Nonselective NSAIDs i 2017 Oct 27 BACKGROUND: Topical NSAIDs have less systemic absorption than oral NSAIDs. We examined the risk of cardiovascular events associated with nonselective topical NSAIDs versus oral NSAIDs among patients with rheumatoid arthritis in Taiwan. METHODS AND RESULTS: We conducted a retrospective cohort study that included patients with incident rheumatoid arthritis who were newly starting therapy with nonselective topical NSAIDs or oral NSAIDs. We used the Taiwan National Health Insurance Research Database (NHIRD). The first date patients received either type of NSAID was defined as the index date. NSAID exposures continued until there was a treatment gap of >30 days. The main outcome was composite cardiovascular events, including myocardial infarction, unstable angina, heart failure, stroke, or revascularization. Follow-up was censored at treatment discontinuation, switch or addition of other NSAID category, cardiovascular outcome, death, or the end of the study. Propensity score weighted Cox regression models were used to compare the risk of cardiovascular events between topical NSAIDs and oral NSAIDs. There were 10 758 and 78 056 treatment episodes for topical and oral NSAIDs identified. After weighting by propensity score, the cohorts were well balanced over all covariates. The crude cardiovascular event rate was 1.87 per 100 person-years for topical NSAIDs and 2.14 per 100 person-years for oral NSAIDs. Results of propensity score weighted Cox regression found the topical NSAID group had 36% lower risk for cardiovascular events compared with the oral NSAID group (hazard ratio, 0.64; 95% confidence interval, 0.43-0.95). CONCLUSIONS: We found topical NSAID users experienced a reduced risk of cardiovascular events compared with oral NSAID users. If future studies with a larger sample size and longer follow-up confirm these results, NSAID prescribing might change accordingly.
27817127 The conversion rate of tuberculosis screening tests during biological therapies in patient 2017 Feb Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory to the initiation of biological therapy in patients with rheumatic diseases. To determine the prevalence of LTBI in patients with rheumatoid arthritis before treatment with biological therapy (anti-TNF, abatacept, and tocilizumab) and the rate of TB conversion during treatment in rheumatoid arthritis (RA) patients, we evaluated the file of 275 patients with RA treated with biological agents. We considered patients with negative baseline TB screening (tuberculin skin test (TST); quantiferon TB gold in tube (QFT-GIT); chest x-ray) and with rescreening for a TB assay every year. Twenty-six patients (10.6%) resulted positive to TB screening at baseline. Two hundred and forty-nine patients (mean age 55.3 ± 11.9; median 55.8 years, range 16-81.9; 210 female) with TB screening negative at baseline were enrolled. One hundred and sixty-eight (67.5%) patients were treated with anti-TNF, 37 (14.9%) patients with abatacept, and 44 (17.7%) patients with tocilizumab. After a period of 12-120 months (median 24), 34 (13.6%) patients displayed conversion of at least one screening assay. Out of the 34 patients with conversion, 6 (16.2%) were treated with abatacept, 7 (15.9%) with tocilizumab, and 21 (12.5%) with anti-TNF. During the follow-up period, no patients developed active TB. Our study shows that a proportion of patients (13.6%) converts at least one TB screening assay during biological therapy. This study underscores the American College of Rheumatology advice for annual screening in some or all biologically treated patients.
29258867 Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis 2018 Feb 1 There are numerous extra- and intra-cellular processes involved in the production of reactive oxygen species (ROS). Augmented ROS generation can cause the damage of biomolecules such as proteins, nucleic acid and lipids. ROS act as an intracellular signaling component and is associated with various inflammatory responses, chronic arthropathies, including rheumatoid arthritis (RA). It is well documented that ROS can activate different signaling pathways having a vital importance in the patho-physiology of RA. Hence, understanding of the molecular pathways and their interaction might be advantageous in the development of novel therapeutic approaches for RA.
29228799 Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activit 2018 Feb OBJECTIVE: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter. METHODS: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52-56 weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2 months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria. RESULTS: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p = .008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p = .0007). The radiographic damage showed no relation to calprotectin. CONCLUSIONS: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.
29268799 Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic dis 2017 Dec 21 OBJECTIVE: Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients' variables to identify risk factors for least significant reduction of bone mineral density. RESULTS: Least significant reduction of lumbar spine bone mineral density (≤ - 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ - 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.
28971583 Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical tri 2018 Mar OBJECTIVES: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. METHODS: Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H(0) : ES = 0 versus alternative hypotheses H(1) : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. RESULTS: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. CONCLUSIONS: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.
28420375 Silent progression in patients with rheumatoid arthritis: is DAS28 remission an insufficie 2017 Apr 19 BACKGROUND: Remission is arguably the ultimate therapeutic goal in rheumatoid arthritis (RA). Applying modern strategies, clinical remission can be achieved in a substantial number of patients with early RA (ERA). Even in those patients, the number and scope of erosions can increase. We, therefore, investigated the value of MRI for the detection of radiological progression in patients with DAS28 improvement and/or clinical remission of the German Remission-plus cohort. METHODS: Data-sets of 80 RA patients (according to 2010 ACR/EULAR criteria) from the Remission-plus study cohort, who fulfilled the following criteria, were retrospectively analysed: availability of two consecutive MRI scans (low-field MRI, follow-up interval 1 year) of the clinically dominant hand and wrist, and the presence of DAS28 (CRP) scores at both time points, which was used to assess disease activity. RESULTS: Seventy-one of the 80 investigated patients presented a numerical improvement of the DAS28 (CRP) after 12 months (DAS28(CRP) T0 average (Ø) 4.96, SD 1.2; DAS28 T4 (12 month) Ø 2.6, SD 1.0), 73% of them also improved in the RAMRIS-Score, while 24% demonstrated an increase despite DAS28 improvement and 3% showed equal values. 48% of patients who improved in the DAS28 reached EULAR remission. 41% of these patients had an increase in the RAMRIS Erosion-subscore after 12 months. When considering EULAR response criteria (non-response (n = 7), moderate response (n = 19), good response (n = 45)), an increase of erosions was found in 71.4% of non-responders, 52.6% of moderate responders, and 31.1% of good responders after 12 months, all compared to baseline. CONCLUSION: Up to 40% of patients in this study demonstrated a progressive erosive disease detected by MRI despite DAS28 improvement or EULAR remission. Future studies are needed to determine the prognostic clinical impact of disease progression in MRI despite clinical remission, and to investigate if DAS28 remission may be an insufficient therapeutic goal and should be accompanied by MRI remission criteria.
28425620 Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vi 2017 Aug Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as a modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis, as well as local expression of cytokines, osteoclast genes, and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL-1, IL-6, and TNF-α, as well as PAD2 and PAD4 enzymes in the periarticular bone marrow. Furthermore, also anti-MCV antibody challenge induced significant periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of patients with rheumatoid arthritis. © 2017 American Society for Bone and Mineral Research.
28672020 Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid a 2017 Patients with rheumatoid arthritis (RA) have an increased mortality rate that is associated with the presence of RA-specific autoantibodies in many studies. However, the relative role of rheumatoid factor (RF), anti-CCP antibodies and the most recently established RA-autoantibodies, directed against carbamylated proteins (anti-CarP antibodies), is unclear. Here, we have assessed the role of these three antibodies in 331 patients with established RA recruited from 2001 to 2009 and followed until November 2015. During this time, 124 patients died (37.5%). This death rate corresponds to a mortality rate 1.53 (95% CI 1.26 to 1.80) folds the observed in the reference population. We used for analysis of all-cause mortality the Cox proportional hazard regression model with adjustment for age, sex and smoking. It showed a trend for association with increased mortality of each of the three RA autoantibodies in antibody-specific analysis (hazards ratio (HR) from 1.37 to 1.79), but only the HR of the anti-CarP antibodies was significant (HR = 1.79, 95% CI 1.23 to 2.61, p = 0.002). In addition, the multivariate analysis that included all autoantibodies showed a marked decrease in the HR of RF and of anti-CCP antibodies, whereas the HR of anti-CarP remained significant. This increase was specific of respiratory system causes of death (HR = 3.19, 95% CI 1.52 to 6.69, p = 0.002). Therefore, our results suggest a specific relation of anti-CarP antibodies with the increased mortality in RA, and drive attention to their possible connection with respiratory diseases.