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ID PMID Title PublicationDate abstract
24134402 Serum vitamin D level and disease activity in patients with recent onset rheumatoid arthri 2016 Apr INTRODUCTION: Rheumatoid Arthritis (RA) is one of the most prevalent autoimmune diseases. Due to the significance of the relationship between serum vitamin D levels and autoimmune diseases, this study aimed to determine the relationship between serum vitamin D level and the severity of disease activity in patients with newly diagnosed RA. METHOD: This cross-sectional study was conducted on 66 patients meeting the American College of Rheumatology - European League Against Rheumatism classification criteria for RA. It was performed in 2012 using simple sampling. The disease activity was measured based on Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) and serum 25-OH vitamin D (25(OH)D) levels using the chemiluminescent immunoassay method. In addition, the levels of ESR and C-reactive protein (CRP), the duration of morning stiffness, and the number of joints with tenderness and swollen were calculated as well. The data were analyzed using the Pearson correlation coefficient. RESULTS: In this study, 10 patients were male (15.2%) and 56 were female (84.8%). The average age of the participants was 45.2 ± 15.3 years. The average level of 25(OH)D in the patients' serum was 30.5 ± 28.9 ng/mL and the mean DAS28-ESR was 5.6 ± 1.1. The correlation coefficient showed that there was an inverse relationship between 25(OH)D and DAS28-ESR, the number of tender and swollen joints, global patient assessment and duration of morning stiffness (P < 0.01). However, the average 25(OH)D level was not related to ESR (P = 0.779) and CRP (P = 0.269). CONCLUSION: The results of this analysis indicated that patients with more active RA have a lower serum vitamin D level.
26162892 Window of opportunity to achieve major outcomes in early rheumatoid arthritis patients: ho 2015 Jul 11 INTRODUCTION: Benefits of disease-modifying anti-rheumatic drugs (DMARD) in early rheumatoid arthritis patients (ERAP) will be achieved if patients follow prescribed treatment. Objective was to investigate whether timing of first non-persistence period and/or duration of persistence during the first 4 years of follow-up predicted disease outcomes at the 5(th) year in a cohort of ERAP, initiated in 2004. PATIENTS AND METHODS: Up to February 2015, charts of 107 ERAP with at least 5 years of follow-up and prospective 6-month assessments of disease activity, disability and persistence were reviewed. Non-persistence was defined as omission of DMARD and/or corticosteroids for at least 7 consecutive days; regarding methotrexate, one weekly missing dose was considered non-persistence. Persistence was recorded through an interview (up to 2008) and thereafter through a questionnaire; persistence duration was recorded in months of continuous medicationtaking. At the 5(th) year, disease activity was defined according to Disease Activity Score (DAS)28, and disability according to Health Assessment Questionnaire (HAQ). Descriptive statistics and linear and Cox regression analyses were used. RESULTS: At study entry, patients were more frequently middle-aged (39.1 ± 13.3 years) and female (88.8%), as well as more likely to have high disease activity and disability. Over the first 4 years of follow-up, 54.2% of the patients had indications for oral corticosteroids and all traditional DMARDs. Almost 70% had at least one period of non-persistence, and their follow-up (median, 25th-75th interquartile range) to first non-persistence period was 13 months (1-31). Persistence duration during the first 4 years predicted subsequent DAS28 (in addition to gender and baseline DAS28) and HAQ (in addition to age). During the 5(th) year, 68 patients (56 women) achieved sustained remission (DAS28 < 2.6). In female population (n = 95), baseline DAS28 (odds ratio [OR], 0.65; 95 % confidence interval [CI], 0.50-0.83; p = 0.001) and persistence duration (OR, 1.04; 95 % CI, 1-1.08; p = 0.05) were predictors. Also, 84 patients achieved sustained function (HAQ <0.21), and baseline DAS28 and age were the only predictors. Timing of first non-persistence period did not impact outcomes. CONCLUSIONS: Persistence duration with DMARDs within the first 4 years of RA predicted subsequent favorable outcomes in ERAP; additional predictors were younger age, male gender and lower disease activity at diagnosis.
26958252 Smartphone Data in Rheumatoid Arthritis - What Do Rheumatologists Want? 2015 OBJECTIVE: To create a relevant and clinically informative visualization of passively collected patient mobility data from smartphones of rheumatoid arthritis (RA) patients for rheumatologists. METHODS: (1) Pilot analysis of smartphone mobility data in RA; (2) Assessment of rheumatologists' needs for patient data through semi-structured interviews; and (3) Evaluation of the visual format of the RA data using scenario-based usability methods. RESULTS: We created a color-scale mobility index superimposed on a calendar to summarize the passive mobility measures from the smartphone that the rheumatologists confirmed would be clinically relevant. CONCLUSION: This assessment of clinician data needs and preferences demonstrates the potential value of passively collected smartphone data to resolve an important data question in RA. Efforts such as these are necessary to ensure that any smartphone data that patients share with their doctors will not exacerbate clinician information overload, but actually facilitate clinical decisions.
25729036 Calprotectin as a biomarker for rheumatoid arthritis: a systematic review. 2015 May OBJECTIVE: Calprotectin (myeloid-related protein 8/14), a heterodimeric complex of calcium-binding proteins, is expressed in granulocytes and monocytes. Calprotectin levels are high in synovial tissue, particularly in activated cells adjacent to the cartilage-pannus junction. This systematic review evaluates the use of calprotectin as an indicator of disease activity, therapeutic response, and prognosis in rheumatoid arthritis (RA). METHODS: Medline, Scopus, and the Cochrane Library (1970-2013) were searched for studies containing original data from patients with RA in whom calprotectin levels were measured in plasma/serum and/or synovial fluid (SF). We included studies examining associations between calprotectin levels and clinical and laboratory assessments, disease progression, and therapeutic response. There were no restrictions for sample size, disease duration, or length of followup. RESULTS: We evaluated 17 studies (1988-2013) with 1065 patients enrolled; 11 were cross-sectional and 8 had longitudinal designs with 2 studies reporting cross-sectional and longitudinal data. Systemic and SF levels of calprotectin were raised in RA. There was a wide range of levels and marked interstudy and intrastudy variability. Calprotectin levels were high in active disease and were particularly high in rheumatoid factor (RF)-positive patients. Levels fell with effective treatment. Longitudinal data showed that calprotectin was a significant and independent predictor of erosive progression and therapeutic responses, particularly in patients who received effective biological treatments. CONCLUSION: SF calprotectin levels are high, suggesting there is substantial local production by inflamed synovium. Blood calprotectin levels, though highly variable, are elevated in active RA and fall with effective therapy. High baseline calprotectin levels predict future erosive damage.
26782542 Effect of sinomenine on the expression of rheumatoid arthritis fibroblast-like synoviocyte 2015 Dec 29 The effect of sinomenine (SIN) on the toll-like receptor (TLR) signal transduction pathway as well as the expression of myeloid differentiation factor 88 (MyD88) and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) was investigated. SIN inhibition of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) proliferation and RA cartilage and subchondral bone destruction was also investigated. RA-FLS were cultured in vitro and the intracellular alkaline phosphatase (ALP) activity was determined in order to obtain the optimal drug concentration. The rate of cell proliferation was determined. Fluorescence quantitative polymerase chain reaction (PCR) was applied to determine the MyD88 and TRAF-6 gene expression and western blot was used to detect the MyD88 and TRAF-6 protein expression. The ALP activity in the SIN groups was lower than that in the control group, among which the 0.5 mM SIN group had the lowest ALP activity (P < 0.01). The rate of RA-FLS proliferation detected by CCK-8 assay in the 0.5-mM SIN group was lower than that in the control group (P < 0.01) and was the highest 4 days after SIN induction. Gene and protein expression of MyD88 and TRAF-6 were downregulated significantly in the 0.5-mM SIN group compared to that in the control group (P < 0.01). SIN effectively inhibited MyD88 and TRAF-6 expression in RA-FLS, which may be one of the important molecular mechanisms involved in RA treatment and prevention of cartilage and subchondral bone destruction.
26402981 New insight into the rheumatoid vasculitis. 2015 Apr Vasculitis in rheumatoid arthritis (rheumatoid vasculitis, RV) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis (RA). While RA affects the body's joints, vasculitis is a condition in which blood vessels become inflamed. Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA. The blood vessels most often involved are arteries that bring blood to the skin, nerves, and internal organs. Veins can also be involved. Rheumatoid vasculitis is skin condition that is a typical feature of RA, presenting as peripheral vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities). The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an autoimmune process is suggested. Compared to other forms of vasculitis, there has been relativejy little research in recent years on the specific entity of RV. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of a better treatment of the underlying RA. In the present review, we discuss the clinical features, laboratory tests, the pathogenesis of RV.
26070937 Power Doppler ultrasound monitoring of response to anti-tumour necrosis factor alpha treat 2015 Oct OBJECTIVES: To monitor by power Doppler US (PDUS) the short-term response to anti-TNFα therapy in six target joints of RA patients; to correlate PDUS findings with clinical assessments and laboratory indices of disease activity. METHODS: Consecutive RA patients starting anti-TNFα therapy were included and studied at baseline and 3 months later. Clinical (number of tender joints; number of swollen joints; Visual Analogue Scale; DAS28) and laboratory (ESR and CRP) assessments were performed. All patients were evaluated by PDUS at six target joints (II MCP, wrist, knee bilaterally). The components of synovitis (synovial hypertrophy, joint effusion, and power Doppler) were analysed and graded (0-3 semi-quantitative score). Moreover, by summing the PDUS findings, three different scores were calculated: a single inflammatory lesion score (0-18, for synovial hypertrophy, effusion, power Doppler), a joint score (0-18; at II MCP, wrist and knee joints) and a global score (0-54; sum of all abnormalities). RESULTS: Sixty-eight RA patients were studied. A significant decrease in the joint score in all articular sites (MCP, P = 0.003; knee, P = 0.002; wrist, P = 0.0001) as well as in the scores of the single components of synovitis (P = 0.0001-0.002) and in the global 6-joint score (P = 0.0001) was found. All clinical and laboratory parameters were significantly decreased at follow-up (P = 0.0001-0.001). A moderate significant positive correlation was observed between the global PDUS score and DAS28 (r = 0.38; P = 0.001). CONCLUSION: PDUS is a sensitive-to-change imaging modality for monitoring the short-term response to anti-TNFα treatment in RA patients. The assessment of a limited number of joints makes the evaluation feasible in rheumatology practice as a complementary tool to clinical assessment.
26633333 A GC-MS Based Metabonomics Study of Rheumatoid Arthritis and the Interventional Effects of 2015 Dec 1 Simiaowan (SMW) is a famous Chinese prescription widely used in clinical treatment of rheumatoid arthritis (RA). The aim of the present study is to determine novel biomarkers to increase the current understanding of RA mechanisms, as well as the underlying therapeutic mechanism of SMW, in RA-model rats. Plasma extracts from control, RA model, and SMW-treated rats were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). An orthogonal partial least-square discriminant analysis (OPLS-DA) model was created to detect metabolites that were expressed in significantly different amounts between the RA model and the control rats and investigate the therapeutic effect of SMW. Metabonomics may prove to be a valuable tool for determining the efficacy of complex traditional prescriptions.
27125075 CERVICAL SPINE LESIONS IN RHEUMATOID ARTHRITIS PATIENTS. 2016 Jan AIM OF THE STUDY: to gather clinical and laboratory data on rheumatoid arthritis patients with cervical spine damage (incidence and prevalence, correlation between duration of disease and the time of lesion onset, to assess signs and symptoms and the role of laboratory investigations). The spine is an axial organ with an important role in support and resistance. It is a pillar with a very complex morphological and functional structure. The vertebral column is crossed by many kinematic chains. The main problem of the cervical spine caused by rheumatoid arthritis is cervical instability which describes all cervical lesions that can lead to neurovascular damage or major disturbance of pain generating statics at movement. The evolving disease shows chronic inflammation of the synovium, which is a self-maintained process and an immunologically induced phenomenon. The chronic inflammation of the synovium forms granulation tissue that invades peripheral joints towards the center and causes ligament cartilage and bone damage. MATERIAL AND METHODS: The present paper investigated cervical spine lesions in 107 rheumatoid arthritis patients who were admitted to the 1st Rheumatology Clinic of Iasi Rehabilitation Hospital between January 2013 and December 2014. Our study focused on assessing signs and symptoms seen in spine affected by rheumatic disease. RESULTS AND DISCUSSIONS: the disease causes destructive lesions due to granulomatous infiltration of rachidian structures and medullary sheaths. These lesions lead to damaged discs and instability that produces subluxations and dislocations. The suboccipital region is most affected; in other regions of the spine, high lesions of C4-C5 prevail, where osteolysis damage of spinal apophyses are found. In atlas and axis joints, rheumatoid arthritis causes the inflammation of bursa, synovium and joint capsule and leads to synovial pannus formation. This causes the destruction of cartilage and subchondral bone. Atlantoaxial dislocation is caused by erosive synovitis of atlanto-epistrophic joint, atlanto-odontoid joint and serous bursitis separating the odontoid process from the transverse ligament. CONCLUSIONS: The dominant symptom of cervical spine damage was pain associated with stiffness and limited joint mobility, muscle stiffness, poor posture.
26753207 Autoantibodies against gliadin in rheumatoid arthritis and primary Sjögren's syndrome pat 2015 INTRODUCTION: Patients with rheumatoid arthritis (RA) and those with primary Sjögren's syndrome (pSS), beside non-specific antibodies, present with organ-specific autoantibodies, including those typical of celiac disease (CD). In the pathogenesis of CD, a role is played by anti-tissue transglutaminase, anti-endomysium, and anti-gliadin (AGA) antibodies. CD can be comorbid with RA and pSS. The aim of the study was to evaluate the prevalence of AGA in RA and pSS patients and discussion of their clinical significance. MATERIAL AND METHODS: The study included 121 patients with RA and 30 patients with pSS. IgG AGA were determined by ELISA method. Additionally, the presence of IgG antimitochondrial antibodies (AMA) was determined in all patients. A further observation included patients with AGA. RESULTS: In the RA group, AGA were detected in five patients (4.1%), and in the pSS group - in two patients (6.7%). All patients in the pSS AGA (+) had AMA and autoimmune thyroid disease (AITD). These differences were statistically significant compared to the pSS AGA (-) and AMA (+) group (p=0.002) and the AGA (-) and AITD (+) group (p=0.003). At the time of the study, none of the patients had been diagnosed with CD. CONCLUSIONS: AGA, typical of CD, are significantly more frequently detected in patients with RA and pSS than in the general population. The presence of autoantibodies may have an impact on the clinical picture of the disease and further medical procedures. CD testing is warranted in selected patients.
26786167 [Genitourinary malignancies and rheumatoid arthritis]. 2016 Feb Genitourinary neoplasms are relatively common and the frequency increases with age. Due to demographic changes more patients with inflammatory rheumatic diseases will have concomitant genitourinary tumors or they will develop them under antirheumatic therapy. In such cases, disease-modifying antirheumatic drugs (DMARD) and immunosuppressive therapy have to be carefully balanced on an individual basis. Based on the limited evidence available large increases in the risks from conventional and/or biological DMARDs for patients with genitourinary malignancies appear to be unlikely for most situations. In addition to these more common situations paraneoplastic symptoms in the musculoskeletal system can occur due to genitourinary malignancies. Moreover, novel drugs with immunostimulating activity for some genitourinary tumors may provoke autoimmune symptoms and thus present new challenges for interdisciplinary cooperation between rheumatologists and uro-oncologists. In this review, the diagnostic procedures, therapies and follow-up of cancers in the field of urology are delineated according to the current German and European guidelines. We describe the core issues that both urologists and rheumatologists should bear in mind. Direct communication, routine exchange and involvement of rheumatologists in interdisciplinary tumor boards should improve future treatment quality of our joint patients.
26713003 Regulatory Effect of Iguratimod on the Balance of Th Subsets and Inhibition of Inflammator 2015 OBJECTIVE: To expand upon the role of iguratimod (T-614) in the treatment of rheumatoid arthritis (RA), we investigated whether the Th1, Th17, follicular helper T cells (Tfh), and regulatory T cells (Treg) imbalance could be reversed by iguratimod and the clinical implications of this reversal. METHODS: In this trial, 74 patients were randomized into iguratimod-treated (group A) and control (broup B) group for a 24-week treatment period. In the subsequent 28 weeks, both groups were given iguratimod. Frequencies of Th1, Th17, Tfh, and Treg were quantified using flow cytometry, and serum cytokines were detected by enzyme-linked immunosorbent assay. mRNA expression of cytokines and transcriptional factor were quantified by RT-PCR. The composite Disease Activity Score, erythrocyte sedimentation rate, and C-reactive protein were assessed at each visit. RESULT: The clinical scores demonstrated effective suppression of disease after treatment with iguratimod. In addition, iguratimod downregulated Th1, Th17-type response and upregulated Treg. Furthermore, the levels of Th1, Th17, and Tfh associated inflammatory cytokines and transcription factors were reduced after treatment with iguratimod, while the levels of Treg associated cytokines and transcription factors were increased.
27568583 Peripheral blood T helper type 17 frequency shows an inverse correlation with disease acti 2016 Dec An increased expansion of T helper type 17 (Th17) cells in the synovium has been shown to play a key role in cartilage and bone destruction in rheumatoid arthritis (RA). Because the correlation of the peripheral blood helper T cell subsets and various inflammatory cytokines with the magnetic resonance imaging (MRI)-based parameters have not been studied adequately to date, we sought to look for the same in this study. RA patients with disease duration less than 36 months, disease-modifying anti-rheumatic drugs (DMARDs) and steroid-naive, were recruited. MRI of the dominant hand and wrist was performed using a 0·2 Tesla MRI machine. Peripheral blood Th1 and Th17 were enumerated by flow cytometry and serum interleukin (IL)-6 and IL-17 by enzyme-linked immunosorbent assay (ELISA). Forty consecutive seropositive RA patients [33 females, mean disease duration 12·2 months, mean disease activity score (DAS)28 = 4·4] were included. MRI revealed erosions in 80% of these subjects. On subgroup analysis, prevalence of erosions (94 versus 68%) as well as mean erosion score (11·5 ± 18·9 versus 3·5 ± 6·0) were significantly higher in established RA (13-36 months' duration) compared to early RA (0-12 months). The median peripheral blood Th17 frequencies were significantly higher in patients (1·4%) compared to healthy controls (0·7%) and had a strong negative correlation with MRI parameters of erosion and osteitis as well as with DAS28 in the established RA subgroup. The frequency of peripheral blood Th17 subset was significantly expanded in established RA which correlated inversely with disease activity as well as MRI based erosions and osteitis.
27451980 Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of 2016 Dec Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies.
25468566 Dopamine receptor DR2 expression in B cells is negatively correlated with disease activity 2015 Mar OBJECTIVE: Dopamine receptor (DR) signaling is involved in the pathogenesis of autoimmune diseases. We aimed to measure the expression levels of DR1-5 on B cells from patients with rheumatoid arthritis (RA) and to analyze the relationship between DRs and clinical manifestations, inflammatory biomarkers, functional status and disease activity. METHODS: A total of 29 patients with RA, 12 healthy donors and 12 patients with osteoarthritis (OA) were recruited in this study. Flow cytometry was used to measure the levels of DR1-5 expressed on B cells. The relationships between B cell DR expressions and clinical features in RA patients were analyzed using the Spearman correlation test. RESULTS: The expression levels of B cell DR1-5 in both the RA and OA groups were lower than those in healthy controls. After 3 months of medication, all five receptors were elevated in RA patients, with DR2 and DR3 being significantly increased from the baseline. DR2 expression on B cells was negatively correlated with inflammatory biomarkers and disease activity. CONCLUSION: RA patients had lower expression level of DR2 on B cells compared to the healthy controls, and the level of DR2 negatively correlated with the disease activity. DR2 and DR3 might be novel predictors of patient responses to disease modifying antirheumatic drug therapy.
26578807 Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell ty 2015 Dec 1 Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14(+) monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6-producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types.
26575982 Efficacy and safety of tofacitinib in US and non-US rheumatoid arthritis patients: pooled 2016 Jan OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post-hoc pooled analysis assessed commonalities and differences in tofacitinib efficacy and safety for US versus rest of the world (ROW) populations. METHODS: Pooled phase (P) III data from patients receiving tofacitinib 5 or 10 mg twice daily (BID) or placebo were assessed for efficacy at Month 3 and for safety outcomes over 12 months. For adverse events of special interest, data on tofacitinib 5 or 10 mg BID or placebo were pooled from six PII and five PIII randomised studies. RESULTS: PIII data were available for 664 vs. 2447 and PII/PIII data for 943 vs. 3567 US vs. ROW patients, respectively. The US population had a higher proportion of Caucasians (81.5% vs. 54.4%), lower proportion of Asians (1.0% vs. 34.6%), and higher mean body weight (85.7 vs. 66.2 kg) and body mass index (31.5 vs. 25.6 kg/m2) compared with ROW. At Month 3, PIII efficacy was similar between US and ROW as assessed by ACR 20/50/70 response rates, remission rates (DAS 28-4[ESR]<2.6), and HAQ-DI scores. Diarrhoea, peripheral oedema, and upper respiratory tract infection occurred in >5% of PIII patients in the US population. Incidence rates for adverse events of special interest were similar between the US and ROW PII/PIII populations. CONCLUSIONS: Patients in the US achieved similar efficacy and safety with tofacitinib 5 and 10 mg BID compared with patients in ROW.
26603928 3D Structure Generation, Molecular Dynamics and Docking Studies of IRHOM2 Protein Involved 2015 A short-lived membrane protein IRHOM2 pedals a cascade of events by regulating Epidermal Growth Factor Receptor (EGFR) signalling in parallel with metalloproteases which results their involvement in cancer as well as in rheumatoid arthritis. Therefore, IRHOM2 is a potential therapeutic drug target for these diseases, but its 3D-structure has not been reported yet. In this study, the three-dimensional structure of the IRHOM2 protein was generated using I-TASSER (Iterative Threading Assembly Refinement) server. The modeled structure of IRHOM2 receptor was validated using various Structural Analysis and Verification Server (SAVES) in which 99.7% of amino acid residues are present in the favoured regions of the Ramachandran Plot. Further, the refined modeled structure was subjected to molecular dynamics simulation & docking analysis. Virtual screening studies were carried out using Glide with various selective libraries containing 24552 compounds and the analysis indicated extensive hydrogen bonding network and hydrophobic interactions which play a significant role in its binding. Docking results were analyzed for high ranking compounds using a consensus based docking score to calculate the binding affinity as a measure of protein-ligand interactions. The top ranking molecule against IRHOM2 active site has a glide g-score of -12.565 kcal/mol and glide e-model score of -74.967 with 3 hydrogen bonds and 11 hydrophobic contacts. This compound may act as probable inhibitor against these chronic diseases but further in vitro studies are required.
25535985 Effects of half dose etanercept (25 mg once a week) on clinical remission and radiographic 2015 Jan OBJECTIVES: This prospective long-term follow-up study evaluated the effects of half-dose etanercept (25 mg weekly) on clinical remission and radiographic progression in a large cohort of patients with rheumatoid arthritis (RA) in clinical remission after etanercept 25 mg bi-weekly. METHODS: 524 biologic-naïve RA patients were treated with etanercept 25 mg bi-weekly after failure of conventional drugs. Patients achieving remission (DAS28 <2.6) for ≥12 months were randomised to receive etanercept 25 mg weekly or 25 mg bi-weekly. Patients were assessed at baseline and every 12 weeks. Remission rates, radiographic progression, incidence of infections and costs of the regimens were compared. RESULTS: After a mean follow-up of 18±11 months, 347 patients (66.2%) achieved DAS28 remission; 323 were randomised to one of two dose regimens: etanercept 25 weekly (group A, 159 patients) and etanercept 25 mg bi-weekly (group B, 164 patients). At the end of follow-up, 81.8% patients of group A maintained remission for a mean of 3.6±1.5 years. Radiographic progression occurred in a small number of patients of group A and the rate of radiographic progression (TSS >0) was not significantly different in the two groups (18.85% vs. 19.0% after the first year and 16.9% vs. 21.6% after the second year, respectively). The incidence ratio of severe infections was 2.3/1.000 patient-years in group A. Etanercept half-dose regimen resulted in a saving of €3.190.545 with a cost saving up to €827.318 per year. CONCLUSIONS: Clinical remission and arrest of radiographic progression persisted in a substantial percentage of patients with RA even after reduction of standard-dose etanercept.
27061835 Reduced corticosteroid-binding globulin cleavage in active rheumatoid arthritis. 2016 Sep OBJECTIVE: Corticosteroid-binding globulin (CBG), the cortisol transport protein, is cleaved from high-affinity (haCBG) to low-affinity (laCBG) CBG at sites of inflammation releasing bioavailable, anti-inflammatory cortisol. Rheumatoid arthritis (RA) is a glucocorticoid-responsive disorder, with paradoxically normal cortisol levels despite elevated inflammatory mediators. Our objective was to determine whether CBG cleavage relates to RA disease activity. We hypothesized that impaired CBG cleavage may limit delivery of free cortisol to inflamed joints in RA. DESIGN: Prospective, cross-sectional observational study. SETTING AND PARTICIPANTS: Fifty-three patients with RA recruited from a Rheumatology outpatient clinic at a tertiary referral centre in Adelaide, Australia, and 73 healthy controls. MEASUREMENTS: Total CBG, haCBG and laCBG, total, free and salivary cortisol, inflammatory markers including interleukin-6 soluble receptor (IL-6sR) and macrophage migration inhibitory factor and clinical measures of disease activity. RESULTS: Among patients with RA, a wide range of disease activity scores was observed (DAS28: range 1·2-6·4). laCBG was lower in patients with RA (mean ± SEM); 153 ± 9, compared with healthy controls; 191 ± 8 nmol/l, P = 0·003. Levels of total and haCBG were higher in patients with more severe RA disease activity. Free and total cortisol, free cortisol:IL-6sR ratio and total cortisol:IL-6sR ratio correlated negatively with disease activity. CONCLUSIONS: These results suggest that patients with RA have reduced CBG cleavage compared to healthy controls and that cleavage is reduced further with higher RA disease activity. Hence, impaired CBG-mediated delivery of endogenous cortisol may perpetuate chronic inflammation in RA.