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ID PMID Title PublicationDate abstract
30121699 Musculoskeletal ultrasound for predicting remission in patients with rheumatoid arthritis: 2018 Oct To assess the role of musculoskeletal ultrasound as a predictor for the achievement of DAS28 remission in patients with rheumatoid arthritis (RA). One hundred and forty-one patients underwent physical and ultrasound examination at five visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint (the German US7 score) was performed on gray scale (GS) and on power Doppler ultrasound (PDUS). The rate of clinical remission and clinical and sonographic predictors for the achievement of DAS28 remission at month 12 were assessed. In the sDMARDs group at month 12, 43.6% of the patients achieved DAS28 remission, 5.1%-SDAI, 3.8%-CDAI, and 3.8%-Boolean remission. In the bDMARDs group, 49.2% achieved DAS28 remission, 6.3%-SDAI, 4.8%-CDAI, and 4.8%-Boolean remission. Predictors for DAS28 clinical remission in the sDMARDs group were low baseline DAS28 (p = 0.002), short disease duration (p = 0.007) and lower baseline PDUS score (p = 0.038). In the bDMARDs group low baseline DAS28 (p < 0.001) and PDUS score (p = 0.035) predicted DAS28 remission. Shorter disease duration, lower baseline DAS28 and PDUS scores are associated with a higher probability of achieving DAS28 remission at month 12 in patients with RA. Musculoskeletal ultrasound and in particular the German US7-scoring system may be used as a predictor for the achievement of clinical remission in RA patients.
29256183 The relationship between the degree of displacement of the atlas to axis and the clinical 2018 Apr INTRODUCTION: The most common type of anatomical cervical spine involvement is atlanto-axial subluxation (AAS) in rheumatoid arthritis (RA). The purpose of this study was to clarify the relationship between the displacement of the atlas to axis and the clinical data obtained in patients with AAS due to RA. METHODS: Fifty patients with AAS due to RA that were treated by surgery are herein reviewed. Based on the findings of preoperative lateral cervical radiographs in the neutral position, the patients were classified into two groups as follows: a 10 + group with an atlanto-dental interval (ADI) of ≧ 10 mm, and a 10 - group with an ADI < 10 mm. RESULTS: Preoperative lateral cervical radiographs demonstrated 15 cases to belong to the 10 + group, while 35 cases belonged to the 10 - group. In the preoperative MR imaging, an intramedullary high signal intensity was observed in seven cases that belonged to the 10 + group and in four cases belonging to the 10 - group. Regarding the neurological severity, the 10 + group included significantly more cases showing severe neurological deficits before surgery; however, there was no significant difference between the two groups regarding the presence of severe deficits even after surgery. CONCLUSIONS: The severe displacement group included significantly more cases showing an intramedullary high signal intensity in the preoperative MR images. Our results also suggest that a severe displacement before surgery affected the presence of neurological deficits before surgery; however, it did not affect the neurological recovery from such severe neurological deficits.
30338636 Relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and disease activity 2018 Dec BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may be used as indicators of inflammatory markers and disease activity due to inflammatory changes in neutrophils, platelets and lymphocytes. Our aim is to investigate the relationship between NLR, PLR ratio and disease activity in RA patients treated with rituximab. METHODS: Thirty-eight patients (8 male, 30 female, mean age 56.8 ± 11.8 years) diagnosed with RA and 30 healthy controls were included in the study. Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), lymphocyte, neutrophil, platelet counts, ESR, C-reactive protein (CRP), PLR, and NLR were evaluated before and after rituximab in RA patients. The relationship between all parameters was assessed by Pearson's correlation, Wilcoxon signed-rank, Mann-Whitney U and paired t tests. RESULTS: The levels of CRP, ESR, and DAS28-ESR decreased significantly at 6 months of rituximab treatment compared to pre-treatment. NLR and PLR ratios were higher in patients with RA than the control group. The median levels were 33.5 mm/hour, 5.7 mg/dL, and 3.7 respectively after 6 months of rituximab treatment. And, the levels were lower than baseline treatment. There was a significant correlation between the levels of DAS28-ESR and NLR, DAS28-ESR and PLR before and after treatment. CONCLUSIONS: The NLR and PLR were higher than healthy controls and correlated with DAS28-ESR in patients with RA. These parameters which are indicative of disease activity decrease with rituximab and correlate with disease activity at 6 months. The NLR and PLR may be useful indices to evaluate RA disease activity treated with rituximab.
30340628 I do not want to suppress the natural process of inflammation: new insights on factors ass 2018 Oct 19 BACKGROUND: It is estimated that 50-70% of patients with rheumatoid arthritis (RA) are non-adherent to their recommended treatment. Non-adherent patients have a higher risk of not reaching an optimal clinical outcome. We explored factors associated with nonadherence from the patient's perspective. METHODS: Four hundred and fifty-nine RA patients (346 (75.4%) females; mean age 63.0 ± 14.8 years) who failed to attend follow-up visits in two rheumatology centres were eligible to participate in a qualitative interview study. We used this strategy to identify patients who were potentially non-adherent to medicines and/or non-pharmacological interventions. By means of meaning condensation analysis, we identified new and some already well known insights to factors associated with non-adherence. We used the capability, opportunity, and motivation model of behaviour (COM-B) model as a frame of reference to classify the factors. RESULTS: Forty-three of 131 patients (32.8%) who agreed to participate in the qualitative interviews were found to be non-adherent. New insights on factors associated with non-adherence included strong opinions of patients, such as pain being considered as an indicator of hard work and something to be proud of, or inflammation being a natural process that should not be suppressed; feeling not to be in expert's hands when being treated by a physician/health professional; the experience of excessive self-control over the treatment; and rheumatologists addressing only drugs and omitting non-pharmacological aspects. The COM-B model comprehensively covered the range of our findings. CONCLUSIONS: The new insights on factors associated with non-adherence allow a better understanding of this phenomenon and can substantially enhance patient care by helping to develop targeted interventions.
30019600 The potential value of rapid, cloud-enabled onsite testing for the diagnosis of rheumatoid 2018 Nov AIMS: Improvements in information technology have granted the recent development of rapid, cloud-enabled, onsite laboratory testing for rheumatoid arthritis (RA). This study aims to quantify the value to payers of such technologies. MATERIALS AND METHODS: To calculate the value of rapid, cloud-enabled, onsite laboratory testing to diagnose RA relative to traditional, centralized laboratory testing, an Excel-based decision tree model was created that simulated potential cost-savings to payers who cover routine evaluations of RA patients in the US. First, a conceptual framework was created to identify the value components of rapid, cloud-enabled onsite testing. Second, value associated with patient time savings, savings on visit fees, change in treatment costs, and QALY improvements was measured, leveraging existing literature and information from an observational study. Lastly, these value components were combined to estimate the total incremental value accruing to payers per patient-year relative to centralized laboratory testing. RESULTS: Rapid, cloud-enabled, onsite testing is estimated to save one office and 1.81 laboratory visits during the evaluation period for the average patient. Results from an observational study found that rapid, cloud-enabled testing increased the likelihood of completing diagnostic orders from 84.5% to 97%, resulting in an increased probability of early treatment (3.5 percentage points) with disease-modifying anti-rheumatic drugs among patients eligible for treatment. The combined total value was $5,648 per evaluated patient-year. This value is primarily attributed to health benefits of early treatment ($5,048), fewer visit payments ($459), and patient time savings due to fewer office ($216) and laboratory visits ($255). LIMITATIONS AND CONCLUSIONS: Data on the impact of rapid, cloud-enabled, onsite testing on patient health, care delivery, and clinical decision-making is scarce. More robust real-world data would confirm the validity of our model. Rapid, cloud-enabled, onsite testing has the potential to generate significant value to payers.
30369929 Profiling of B-Cell Factors and Their Decoy Receptors in Rheumatoid Arthritis: Association 2018 Introduction: B-cell activation is pivotal in rheumatoid arthritis (RA) pathogenesis and represents a relevant therapeutic target. The main aim of this study was to characterize the profiles of B-cell factors and their decoy receptors in RA and evaluate their clinical relevance. Methods: sBLyS, sAPRIL, sBCMA, sTACI, sBLyS-R, and several cytokines' serum levels were measured by immunoassays in 104 RA patients and 33 healthy controls (HC). An additional group of 42 systemic lupus erythematosus (SLE) patients were enrolled as disease controls. Whole blood IFI44, IFI44L, IFI6, and MX1 gene expression was measured and averaged into an IFN-score. BLyS membrane expression (mBLyS) was assessed on blood cell subsets by flow cytometry. Results: increased sAPRIL and sBCMA levels were found in RA, whereas BLyS was elevated in very early RA (VERA). No differences were observed for sTACI and sBLyS-R. An increased sBLyS/sBLyS-R ratio was associated with poor clinical outcome at 6 and 12 months in VERA, whereas a positive association with disease activity was observed in established disease. Increased mBLyS expression was found on monocytes, mDCs, neutrophils and B-cells in RA, to a similar extent that in SLE patients. Cluster analysis identified a specific B-cell factors profile overrepresented in RA and associated with autoantibodies, elevated proinflammatory cytokines (IFNα, MIP1α, TNFα, IL-37, and GM-CSF) and increased type-I IFN signature. Increasing sBCMA and sBLyS serum levels upon treatment and mBLyS expression at baseline on monocytes and mDCs, but not B-cells, were associated with poor clinical outcome upon TNFα-blockade. Conclusions: profound and complex alterations of soluble and membrane-bound B-cell factors are observed in RA associated with clinical outcomes, thus supporting its applicability to guide patient stratification along disease course.
29351859 Structural and immunological characterization of hydroxyl radical modified human IgG: Clin 2018 Apr 5 Structural alterations in proteins under oxidative stress have been widely implicated in the immuno-pathology of various disorders. This study has evaluated the extent of damage in the conformational characteristics of IgG by hydroxyl radical (OH) and studied its implications in the immuno-pathology of rheumatoid arthritis (RA). Using various biophysical and biochemical techniques, changes in aromatic microenvironment of the IgG and the protein aggregation became evident after treatment with OH. The SDS-PAGE study confirmed the protein aggregation while far ultraviolet circular dichroism spectroscopy (Far-UV CD) and fourier transform infrared spectroscopy (FTIR) inferred towards the alterations in secondary structure of IgG under OH stress. Dynamic light scattering showed that the modification increased the hydrodynamic radius and polydispersity of IgG. The free arginine and lysine content reduced upon modification. OH induced aggregation was confirmed by enhanced thioflavin-T (ThT) fluorescence and red shift in the congo red (CR) absorbance. The study on experimental animals reiterates the earlier findings of enhanced immunogenicity of OH treated IgG (OH-IgG) compared to that of native IgG. OH-IgG strongly interacted with the antibodies derived from the serum of 80 rheumatoid arthritis (RA) patients. The overwhelming and strong tendency of OH-IgG to bind the antibodies derived from the serum of RA patients points towards the modification of IgG under patho-physiological conditions in RA that generate neo-epitopes and eventually cause the generation of auto antibodies that circulate in the patient sera. Further studies on this aspect may possibly lead to the development of a biomarker for RA.
29393388 Hypoxia‑induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of f 2018 Apr Impaired apoptosis of rheumatoid arthritis (RA)‑fibroblast‑like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the apoptosis of RA‑FLS. FLS were isolated from patients with RA and a rat model. The effects of PADI4 on RA‑FLS were investigated in vitro and in vivo. Hypoxia‑induced autophagy was induced by 1% O2 and was detected by immunohistochemical and immunofluorescence analysis; in addition, apoptosis was detected by flow cytometry. RA‑FLS obtained from RA rat model exhibited significant proliferation under severe hypoxia conditions. Hypoxia also significantly induced autophagy and elevated the expression of PADI4. Subsequently, short hairpin RNA‑mediated PADI4 knockdown was demonstrated to significantly inhibit hypoxia‑induced autophagy and promote apoptosis in RA‑FLS. The results of these in vitro and in vivo studies suggested that PADI4 may be closely associated with hypoxia‑induced autophagy, and the inhibition of hypoxia‑induced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RA‑FLS.
29882203 Niclosamide as an adjuvant to etanercept in treatment patients with active rheumatoid arth 2018 Oct This study designed to identify the therapeutic efficacy of niclosamide (NCL) in Iraqi patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA. One hundred ten patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA were allocated randomly into two equal groups: one of them treated with 1000 mg/day NCL and the other treated with 1000 mg/day lactose in capsule dosage form. The study duration was 8 weeks. Clinical efficacy of the NCL was measured depending on scoring of the 28-joint Disease Activity Score (DAS28), simple disease activity index (SDAI), clinical disease activity index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) at the baseline and at the end of the 8-week treatment period. Moreover, blood sample were taken from the patients at baseline and at after 8 weeks of treatment for measurement of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin 1β (IL-1 β), interleukin-6, tumor necrosis factor (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. At the end of the clinical study, patients had good response to NCL when added to the ETN with a high significant improvement in the SJC, TJC, DAS-28, CDAI, SDAI, and HAQ-DI compared to patients who were received placebo drug. In addition to that, 33% of patients achieved an ACR 20% response (ACR20) on NCL and ETN. Of these, 4% achieved ACR50 and another 4% achieved ACR70 response. While those group treated by placebo + ETN, 5% achieved ACR20 response and no one reached to ACR50 or ACR70 response. Twenty-seven percent of RA patients who have taken the NCL achieved moderate EULAR score while only 17% from the group that taken placebo with ETN achieved moderate response. On the other hand, no significant reduction was found in CRP, ESR, TNF-α, and IL-6, while IL-1 β reduced significantly after treatment with NCL. Treatment with NCL also exerts a significant lowering in the serum level of the E-selectin, ICAM1, and VCAM1 when compared to their value in baseline level. In RA disease, the use of NCL as adjuvant with ETN has resulted in a marked reduction in clinical assessment scoring indices and significantly decreased the E-selectin, ICAM-1, and VCAM-1 with marked improvement in the quality of life of patients.
28160411 Active synovitis in the presence of osteitis predicts residual synovitis in patients with 2018 Oct AIM: To clarify the relationship between active synovitis/osteitis and subsequent residual synovitis (R-synovitis) in patients with rheumatoid arthritis (RA). METHODS: Three hundred and twenty finger joints of 16 patients with active RA at baseline (Disease Activity Score with 28 joints - erythrocyte sedimentation rate > 3.2) who subsequently achieved clinical low disease activity or remission afterwards were analyzed. Synovial vascularity (SV) was assessed according to a semi-quantitative ultrasound score (grades 0-3). Active synovitis was defined by SV positivity at baseline. R-synovitis was defined by the presence of grade > 2 SV at the 24th week. Osteitis was detected by magnetic resonance imaging (MRI) at baseline as trabecular bone lesions with water content and indistinct margins. RESULTS: Ultrasonography detected active synovitis in 116 joints at baseline. Forty-seven joints had R-synovitis at the 24th week. MRI detected osteitis in 12 joints at baseline. The presence of active synovitis with osteitis at baseline was significantly correlated with R-synovitis at the 24th week. CONCLUSIONS: Active synovitis in the presence of osteitis predicted R-synovitis regardless of whether there was a clinical improvement in RA.
29542420 Insulin-Sensiting Effects of Tumor Necrosis Factor Alpha Inhibitors in Rheumatoid Arthriti 2018 BACKGROUND: Rheumatoid Arthritis (RA) has been associated with insulin resistance (IR), a well-established pathophysiological feature of Type 2 Diabetes (T2DM). Inconsistent literature evidence suggests that IR could be ameliorated by biological medications targeting TNFα. OBJECTIVE: The aim of this systematic review was to evaluate the effect of TNFα inhibitors (TNFi) on IR in RA patients. METHODS: We performed a systematic review in order to identify the available data on the effect of anti- TNFα medications on IR in RA patients. For this purpose, MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and SCOPUS were searched up to December 2016. RESULTS: The search strategy retrieved 209 individual records. Of these, only 12 articles were included in the systematic review. The pooled analysis under a random-effects model demonstrated a significant improvement of IR after treatment with TNFi quantified with the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR), with a standardized difference in means (SDM) of -0.847 (95%CI: -1.278 - 0.417, p < 0.0001). Heterogeneity across studies was high (Q = 65.00 with df = 9, p < 0.001, I2 = 89.15%). CONCLUSION: Our meta-analysis suggests that TNFα blockade might improve IR in RA patients.
29325472 Latent psychological distress existing behind a set of assessment measures is comparable t 2018 Nov OBJECTIVES: To identify the determinant of patients' perspectives of quality of life (QOL) and working status out of analysis-derived components underlying a set of assessment measures of the status of patients with rheumatoid arthritis (RA). METHODS: From the NinJa database in Japan (2012-2014), 1455 RA patients with DAS28 > 3.2 were recruited. Components explaining RA status were derived from principal component analysis of 15 assessment measures. Multivariate regression was used to examine the relative contribution of each identified component to the EuroQOL-5 Dimension Questionnaire score and working status. RESULTS: Among the identified components (patient symptoms, physical disability, evaluated symptoms, patient distress, inflammatory marker, and serological marker), patient distress showed highest contribution to EuroQOL for both male (44.6%) and female patients (39.3%). Physical disability was associated with significantly less participation in paid work in male (odds ratio [OR]; 0.63) and both household and paid work in female (OR; 0.82 and 0.54, respectively), though patient distress showed the strongest association with less participation in both household and paid work in female (OR; 0.64 and 0.45, respectively). CONCLUSION: The approach to latent patient distress using psychological screening tools, concurrently with the treatment to control the activity of arthritis, can be help to improve health-related QOL (HRQOL) including work participation.
28511288 Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthriti 2018 Mar OBJECTIVE: To test the effect of patient-reported outcome (PRO)-based tele-health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health followup performed by rheumatologists or rheumatology nurses. METHODS: A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health followup carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self-efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent-to-treat (ITT), and multivariate imputation analysis. RESULTS: Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO-TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and -0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO-TN had mean ± SD 1.72 ± 1.03 visits/year, PRO-TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare. CONCLUSION: Among RA patients with low disease activity or remission, a PRO-based tele-health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.
29210204 Validation and reliability of the Timed Up and Go test for measuring objective functional 2018 Oct AIM: This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. RESULTS: A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). CONCLUSION: TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.
30001740 The role of anti-citrullinated protein antibody reactivities in an inception cohort of pat 2018 Jul 13 BACKGROUND: Anti-citrullinated protein antibody (ACPA) reactivities precede clinical onset of rheumatoid arthritis (RA), and it has been suggested that ACPA reactivities towards distinct target proteins may be associated with differences in RA phenotypes. We aimed to assess the prevalence of baseline ACPA reactivities in an inception cohort of patients with early RA, and to investigate their associations with disease activity, treatment response, ultrasound findings and radiographic damage. METHODS: Disease-modifying antirheumatic drug (DMARD)-naïve patients with early RA, classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, were included in the ARCTIC trial and assessed in the present analysis. During follow up, patients were monitored frequently and treatment was adjusted according to a predetermined protocol, starting with methotrexate monotherapy with prednisolone bridging. Analysis of 16 different ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase, vimentin, filaggrin and histone was performed using a multiplex chip-based assay. Samples from 0, 3, 12 and 24 months were analysed. Controls were blood donors with similar characteristics to the patients (age, gender, smoking status). RESULTS: A total of 217 patients and 94 controls were included. Median [25, 75 percentile] number of ACPA reactivities in all patients was 9 [4, 12], and were most prevalent in anti-cyclic citrullinated peptide /rheumatoid factor-positive patients 10 [7, 12]. Disease activity measures and ultrasound scores at baseline were lower in ACPA reactivity-positive compared to ACPA reactivity-negative patients. ACPA reactivity levels decreased after 3 months of DMARD treatment, most pronounced for fibrinogenβ 60-74 to 62% of baseline antibody level, with least change in filaggrin 307-324 to 81% of baseline antibody level, both p < 0.001. However, outcomes in disease activity measures, ultrasound and radiographic scores after 12 and 24 months were not associated with baseline levels or changes in ACPA reactivity levels and/or seroreversion after 3 months. CONCLUSIONS: The clinical relevance of analysing ACPA reactivities in intensively treated and closely monitored early RA was limited, with no apparent associations with disease activity, prediction of treatment response or radiographic progression. Further studies in larger patient materials are needed to understand the role of ACPA reactivities in patients with RA classified according to the 2010 ACR/EULAR criteria and treated according to modern treatment strategies. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01205854 . Registered on 21 September 2010.
28828748 Relationship between matrix metalloproteinase-3 serum level and pulmonary artery systolic 2018 Feb Activity of rheumatoid arthritis (RA) has been evaluated by various biomarkers including matrix metalloproteinase (MMP)-3, but the relationship between the levels of biomarkers and elevation of pulmonary artery systolic pressure (PAs) has not been evaluated in detail. We sought to determine the utility of MMP-3 with other biomarkers for the prediction of PAs in patients with RA. Blood samples for biomarkers and echocardiography were obtained in 100 consecutive patients with RA. PAs was measured by continuous-wave Doppler echocardiography and was correlated with laboratory findings. PAs had a fair correlation with MMP-3 (r = 0.53, p < 0.001) and a weak correlation with KL (Krebs von den Lungen)-6 (r = 0.36, p < 0.001) and rheumatoid factor (r = 0.25, p = 0.011). MMP-3 had a fair correlation with pulmonary vascular resistance (r = 0.42, p < 0.001), but MMP-3 was not related to cardiac output (r = 0.09, p = 0.352). Thirty-nine patients had impaired left ventricular diastolic function. There was no significant differences in PAs and pulmonary vascular resistance (PVR) between the patients with and without impaired left ventricular diastolic function. When 5 variables (age, MMP-3, C-reactive protein, KL-6, and rheumatoid factor) were used in the multivariate analysis, MMP-3 (partial regression coefficient = 0.553, p < 0.001) emerged as the most important variable related to the elevation of PAs. Nine patients (9%) were diagnosed to have pulmonary hypertension by echocardiography. MMP-3 value of 245 ng/ml was the optimal cut-off value for the prediction of pulmonary hypertension (sensitivity: 100%, specificity: 67%, area under the curve 0.89). Thus, a close relation of MMP-3 with PAs and PVR indicate that rise in PAs in patients with RA was ascribed to increase in PVR due to underlying systemic inflammation-mediated pulmonary vascular remodeling.
28117013 Gray Scale and Power Doppler Ultrasonographic Findings in the Assessment of Disease Activi 2018 OBJECTIVES: To study the utility of gray scale and power Doppler ultrasonography in assessing the disease activity and correlation of ultrasonographic findings with disease activity parameters in Rheumatoid Arthritis (RA). MATERIALS AND METHODS: This cross-sectional study was conducted on 100 RA patients diagnosed as per 2010 classification criteria. Rheumatoid Factor (RF), serum Anti-cyclic Citrullinated Peptide Antibodies (ACPA), Erythrocyte Sedimentation Rate (ESR), C-reactive Protein (CRP), disease activity score with 28-joint counts and ESR (DAS28-ESR), Visual Analogue Scale (VAS) for global disease activity and Gray Scale Ultrasonography (GSUS) and Power Doppler Ultrsonography (PDUS) scores in hands and wrists were determined. RESULTS: Of 100 RA patients with clinically active arthritis, GSUS detected disease activity in all and PDUS in 95 (95%) patients. Of total 2200 joints assessed, disease activity was seen by clinical assessment in 51.31% (1116/2200), GSUS in 57.36% (1262/2200) and PDUS in 48.36% (1064/2200) joints. For detecting active arthritis, clinical assessment showed 79.5% sensitivity and 76.2% specificity while GSUS showed 100% sensitivity and 82.5% specificity using PDUS as a gold standard. GSUS findings of synovitis, joint effusion and bone erosions and PDUS score showed significant correlations with the swollen joint count, tender joint count, ESR and DAS28- ESR (p<0.05 each) but not with VAS, CRP, RF and ACPA (p>0.05 each). Multivariate analysis showed that swollen joint count was independently associated with synovitis (p=0.029) and tender joint count with PDUS score (p=0.036). CONCLUSIONS: GSUS and PDUS findings are useful in ascertaining the disease activity and correlate with clinical disease activity in joints in RA.
29913256 The effect of glucocorticoids on bone mineral density in patients with rheumatoid arthriti 2018 Sep PURPOSE: The role of glucocorticoids in the treatment of rheumatoid arthritis (RA) is widely debated. Impairment of bone formation may be counter-balanced by reduced systemic inflammation. This review aims to assess the effect of prednisolone/prednisone on bone mineral density (BMD) in patients with RA analyzed in randomized, controlled trials. METHODS: We performed a systematic literature search and identified randomized, double-blinded placebo-controlled studies including patients with RA and using prednisolone or prednisone as the intervention. We selected studies that measured BMD by DXA at baseline and at least once thereafter. Two authors independently performed reference review, data extraction and risk of bias assessment. Primary outcome was mean change in BMD from baseline to follow-up. Secondary endpoints included radiographic scores, RA disease activity indices and fractures. We rated the quality of evidence using the GRADE approach. Outcomes were standardized for meta-analyses and 95% confidence intervals (95% CI) were calculated. RESULTS: We identified 7 studies and included previously unpublished data. Studies were similar regarding study population and intervention. Standard mean difference (SMD) in change in BMD from 0 to 24 months was -0.02 (95%CI -0.16, 0.12) at the lumbar spine and -0.11 (95% CI -0.25, 0.02) at the hip (both high quality evidence) between patients treated with prednisolone/prednisone or not. Data completeness was low in some studies, concomitant treatment of RA differed between studies and differences in use of anti-osteoporotic medication may have influenced the results. However, sensitivity analyses excluding studies in which participants used either the most or the least potent concomitant RA treatment or used anti-osteoporotic therapies did not alter the estimates. CONCLUSIONS: In patients with early and active RA, we found no difference in change in BMD between patients treated with prednisone/prednisolone versus placebo, suggesting that at least through 24 months, the suppression of inflammation by glucocorticoids may counterbalance their adverse effects on bone remodeling.
28850021 Suppression of active, but not total MMP-3, is associated with treatment response in a pha 2018 Jan OBJECTIVE: Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a commonly measured biomarker in rheumatology. The aim was to investigate the association of activated MMP-3 (actMMP3) species with treatment response compared to cMMP-3. METHODS: The LITHE biomarker study (n=741) was a 1-year phase III, double-blind, placebo-controlled, parallel group study of TCZ in RA patients on stable methotrexate. cMMP-3 and actMMP-3 were assessed in fasting serum at baseline, week 4, 16, 24 and 52. Patients not achieving ACR20 remission at week 16 or 28 received rescue treatment (escapers). Spearman's correlation was analysed between biomarker baseline level or biomarker delta and clinical measures. Changes in biomarker levels were studied as a function of time and treatment. RESULTS: ActMMP-3 16-week change in treatment groups was predictive of 1-year radiographic progression; a small change in actMMP3 was equal to worsening radiographics. Baseline cMMP-3 was associated with 52-weeks' radiographic status and cMMP3 16-weeks' change was predictive of 1-year change in disease activity. ActMMP-3 was dose-dependently decreased by TCZ, and escapers decreased in actMMP-3 upon treatment. CONCLUSIONS: ActMMP-3 and cMMP-3 were found to be efficacy biomarkers of TCZ and actMMP-3 were able to differentiated doses. Moreover, the suppression of actMMP3, but not cMMP3 was associated with treatment response. This study illustrates that two biomarkers of the same protein may have different predictive capacities.
29991120 A useful marker in the assessment of remission and activation of disease in patients with 2018 AIM: Rheumatoid arthritis (RA) is a chronic disease of unknown etiology. Various cellular and molecular immunological factors are involved in the pathophysiology of RA. Recent studies suggest that neutrophils and alpha-defensins released from the neutrophils assume significant roles in the pathogenesis of RA. The aim of this study was to investigate the potential association between serum alpha-defensin levels and disease activity, functional status, radiological damage and several laboratory parameters in patients with RA. MATERIALS AND METHODS: A total of 42 patients with established RA who presented to the outpatient clinics of rheumatology of Dicle University Hospital and 38 healthy control subjects were included in this study. Disease activity was assessed by using the Disease Activity Scale 28 (DAS28). Quality of life was assessed by using the Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire and the Nottingham Health Profile (NHP). Functional status was assessed by using the Stanford Health Assessment Questionnaire (HAQ). Laboratory examinations included the following tests: CBC, ESH, CRP, and HNP 1-3. RESULTS: Patients with an active disease exhibited higher HNP 1-3 levels compared to patients in remission. At a cut off value of 708 pg/ml, sensitivity and specificity of the tests for HNP 1-3 were 72% and 70.6%, respectively. CONCLUSION: In the present study, patients with an active disease had significantly higher serum HNP 1-3 levels compared to patients in remission. In this respect, serum HNP 1-3 can be a useful marker in the assessment of disease activity and remission in patients with RA.