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ID PMID Title PublicationDate abstract
25960615 Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives. 2015 Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.
25602164 Lipid extract from hard-shelled mussel (Mytilus coruscus) improves clinical conditions of 2015 Jan 16 Studies have suggested a lipid extract from hard-shelled mussel (Mytilus coruscus) (HMLE) possessed strong anti-inflammatory activity in arthritis model of rats. This study investigated whether HMLE could improve clinical conditions of rheumatoid arthritis patients. Fifty rheumatoid arthritis patients (28-75 years) were randomly assigned to receive HMLE capsules or receive placebo capsules for 6 months. Forty-two subjects and 50 subjects were included in per-protocol and intention-to-treat analysis, respectively. Significant differences in changes on disease activity score (DAS28) and clinical disease activity index (CDAI) after 6-month intervention (p < 0.01) were observed in both analyses with more evident efficacy shown in per-protocol population (∆DAS28 = 0.47; ∆CDAI = 4.17), which favored the benefits of the HMLE group. TNF-α (tumor necrosis factor α), interleukin (IL)-1β and PGE2 (prostaglandin E2) but not IL-6, were significantly decreased in both groups, and the decrements were much larger in the HMLE group for TNF-α and PGE2 after 6 months from baseline (p < 0.05). IL-10 was significantly increased in both groups and the change was much more evident in the HMLE group (p < 0.05). In conclusion, HMLE exhibited benefits for the clinical conditions of rheumatoid patients in relation to improvement in the balance between pro- and anti-inflammatory factors, which indicated its potential to serve as adjunctive treatment for rheumatoid arthritis. (ClinicalTrials.gov NCT02173587).
27974367 Hand-related physical function in rheumatic hand conditions: a protocol for developing a p 2016 Dec 14 INTRODUCTION: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. METHODS AND ANALYSIS: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach. ETHICS AND DISSEMINATION: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences.
26560983 Incidence of active mycobacterial infections in Brazilian patients with chronic inflammato 2015 Nov Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.
25462274 Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial di 2015 Jan 7 Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis.
27942977 Maintenance of efficacy and safety with subcutaneous golimumab in rheumatoid arthritis pat 2017 Apr The study was conducted to evaluate continued maintenance of the efficacy and safety of therapy by switching to subcutaneous golimumab (GLM-SC) in rheumatoid arthritis patients with low disease activity or remission who previously received a tumor necrosis factor (TNF) inhibitor. Thirty patients who had been treated with etanercept or infliximab were switched to GLM-SC in maintaining disease activity at a low level. The patients were divided into two groups through discussion with each patient, considering general condition and convenience: the low disease activity (LDA) group and the LDAq8w group, which included patients with low disease activity or remission who switched to 50 mg GLM therapy at 4- and 8-week intervals, respectively. The effects of the TNF inhibitors to GLM-SC switch were evaluated at 12, 24, and 52 weeks after switching. The mean DAS28-ESR and DAS-CRP values in the LDA groups (16 patients) and LDAq8w groups (14 patients) were maintained from baseline throughout the 52-week treatment period. DAS28-ESR remission (93.8 and 92.3%) rates were also maintained through week 52 from the baseline remission rate (75.0 and 78.6%) in the LDA and LDAq8w groups, respectively. Thus, both GLM-SC treatment regimens were effective in maintaining the clinical response achieved with LDA secondary to TNF inhibitors. No serious adverse events occurred, and the continuation rate at 52 weeks was 100% in both groups. Therapeutic efficacy is adequately maintained in most patients switching from TNF inhibitor to GLM-SC (50 mg/4-8 weeks). Patients receiving TNF inhibitor can seamlessly switch to GLM-SC without serious safety concerns.
24816341 Health related quality of life in rheumatoid arthritis, osteoarthritis, diabetes mellitus, 2015 Mar INTRODUCTION: Chronic diseases have a great impact in the morbidity and mortality and in the health-related quality of life (HRQoL) of patients around the world. The impact of rheumatic diseases has not been fully recognized. We conducted a comparative study to evaluate the HRQoL in different chronic diseases. OBJECTIVES: The aim of the present study was to assess the HRQoL and identify specific areas affected in patients with rheumatoid arthritis (RA), osteoarthritis (OA), diabetes mellitus, end-stage renal disease, geriatric subjects and a control group. PATIENTS AND METHODS: We conducted a cross-sectional study, in a General Hospital in Morelia, Mexico. All patients met classification criteria for RA, OA, diabetes mellitus, end-stage renal disease; the geriatric subjects group was≥65 years, and the control group≥30 years. Demographic characteristics were recorded, different instruments were applied: SF-36, visual analogue scale for pain, patient's and physician's global assessments, Beck Depression Inventory and specific instruments (DAS-28, HAQ-Di, WOMAC, Diabetes Quality of Life [DQOL] and Kidney Disease Questionnaire of Life [KDQOL]). Biochemical measures: erythrocyte sedimentation rate, blood count, glucose, HbA1C, serum creatinine and urea. RESULTS: We evaluated 290 subjects (control group: 100; geriatric subjects: 30 and 160 for the rest of groups). Differences were detected in baseline characteristics (P<.0001). The SF-36 scores were different between control group and others groups (P=0.007). The worst HRQoL was in end-stage renal disease group (±SD: 48.06±18.84 x/SD). The general health was the principal affected area in RA. The pain was higher in rheumatic diseases: OA (5.2±2.4) and RA (5.1±3). HAQ was higher in OA compared to RA (1.12±0.76 vs 0.82±0.82, respectively; P=.001). Forty five percent of all subjects had depression. CONCLUSIONS: The HRQoL in RA patients is poor and comparable to other chronic diseases (end-stage renal disease and diabetes mellitus). Rheumatic diseases should be considered high impact diseases and therefore should receive more attention.
26087636 [Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-in 2015 AIM: To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. RESULTS: According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. CONCLUSION: Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.
25534463 [Sarcoidosis after adalimumab treatment in inflammatory rheumatic diseases: a report of tw 2015 Jan CONTEXT: TNF α antagonists (anti-TNF α) are widely used in inflammatory rheumatic diseases: rheumatoid arthritis (RA) and spondylarthropathy (SpA). The efficacy of the anti-TNF α monoclonal antibodies was also observed in unresponsive sarcoidosis to conventional therapy. In contrast, sarcoidosis in patients with inflammatory rheumatic disease treated with anti-TNF α keep on growing, with a suspected role of anti-TNF α in this pathological process. METHODS: We presented here two cases of sarcoidosis developing while the patient was on adalimumab (ADA) therapy for inflammatory rheumatic disease. In one case, the reintroduction of ADA led to increase in symptomatology. We also analyzed the 16 other cases of sarcoidosis developing under ADA treatment published in literature, mostly in RA patients. RESULTS: These cases show a possible paradoxical effect of ADA in sarcoidosis development in patients treated with anti-TNFα monoclonal antibodies. The iatrogenic mechanism remains unclear. These cases underline the importance of a drug-induced etiology survey facing any symptomatology suggesting the development of sarcoidosis in patients treated with anti-TNF α for an inflammatory rheumatic disease.
26242731 Use of intraoperative fluoroscopy for the safe placement of C2 laminar screws: technical n 2015 Dec INTRODUCTION: Rigid fixation of the atlantoaxial joint can be quite challenging due to complex anatomic variants. Numerous techniques have evolved over time, improving the surgeon's adaptability. The recent advent of C2 laminar screws adds to the surgeon's armamentarium, but is not without its own set of limitations. Risk of ventral laminar breach with possible spinal cord injury, CSF leak, or poor bony fixation have led some to recommend prefabricated models or expensive intraoperative spinal navigation to aid screw placement. The purpose of this report is to detail how the use of intraoperative fluoroscopy can be used to aid in the safe placement of C2 laminar screws. METHODS: One patient with rheumatoid arthritis and progressive cervical myelopathy from C1-2 instability underwent C1-2 fixation using C2 laminar screws. Intraoperative fluoroscopy was used to guide and confirm safe laminar screw placement. RESULTS: Immediate and 6-month postoperative imaging demonstrated excellent placement of C2 laminar screws without ventral breach. At 6 months, the patient noted significant improvement of her preoperative symptoms. CONCLUSION: Use of intraoperative fluoroscopy is an easy and safe method for the placement of C2 laminar screws. Given its use of readily available equipment, this method can be implemented without significant pre-planning, or as an impromptu salvage maneuver.
27113415 Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treate 2016 Oct OBJECTIVE: To evaluate the risks of herpes zoster (HZ) and herpes simplex virus (HSV) infection associated with tofacitinib compared with biologic agents among patients with rheumatoid arthritis (RA). METHODS: Using health plan data from 2010 to 2014, patients with RA initiating tofacitinib or biologics with no history of HZ or HSV were identified, as were incident cases of HZ or HSV. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV. RESULTS: A total of 2526 patients initiating tofacitinib were compared with initiations of other biologics: anti-tumour necrosis factor (TNF) (n=42 850), abatacept (n=12 305), rituximab (n=5078) and tocilizumab (n=6967). Patients receiving tofacitinib were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant methotrexate (MTX) (39% vs 43%-56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100 patient-years (py). After multivariable adjustment, HZ risk was significantly elevated, HR 2.01 (95% CI 1.40 to 2.88) compared with abatacept. Rates and adjusted HRs for all other RA biologics were comparable with each other and abatacept. Older age, female sex, prednisone >7.5 mg/day, prior outpatient infection and greater number of hospitalisations were also associated with increased HZ risk. Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100 py) and also significantly elevated after adjustment (HR=1.40, 95% CI 1.09 to 1.81). CONCLUSIONS: The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics.
27278240 Ultra-low-dose CT Imaging of the Thorax: Decreasing the Radiation Dose by One Order of Mag 2016 Nov Computed tomography (CT) is an indispensable tool for imaging of the thorax and there is virtually no alternative without associated radiation burden. The authors demonstrate ultra-low-dose CT of the thorax in three interesting cases. In an 18-y-old girl with rheumatoid arthritis, CT of the thorax identified alveolitis in the posterior costophrenic angles (radiation dose = 0.2 mSv). Its resolution was demonstrated on a follow-up scan (4.2 mSv) performed elsewhere. In an 11-y-old girl, CT (0.1 mSv) showed changes of the right collar bone consistent with chronic recurrent multifocal osteomyelitis. CT (0.1 mSv) of a 9-y-old girl with mucopolysaccharidosis revealed altogether three hamartomas, peribronchial infiltrate, and spine deformity. In some indications, the radiation dose from CT of the thorax can approach that of several plain radiographs. This may help the pediatrician in deciding whether "gentle" ultra-low-dose CT instead of observation or follow-up radiographs will alleviate the uncertainty of the diagnosis with little harm to the child.
27428849 Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake: A Sy 2016 Oct 4 BACKGROUND: Mediterranean diets may be healthier than typical Western diets. PURPOSE: To summarize the literature comparing a Mediterranean diet with unrestricted fat intake with other diets regarding their effects on health outcomes in adults. DATA SOURCES: Ovid MEDLINE, CINAHL, and the Cochrane Library from 1990 through April 2016. STUDY SELECTION: Controlled trials of 100 or more persons followed for at least 1 year for mortality, cardiovascular, hypertension, diabetes, and adherence outcomes, as well as cohort studies for cancer outcomes. DATA EXTRACTION: Data extracted by 1 investigator was verified by another. Two reviewers assessed risk of bias and strength of evidence. DATA SYNTHESIS: Two primary prevention trials found no difference in all-cause mortality between diet groups. One large primary prevention trial found that a Mediterranean diet resulted in a lower incidence of major cardiovascular events (hazard ratio [HR], 0.71 [95% CI, 0.56 to 0.90]), breast cancer (HR, 0.43 [CI, 0.21 to 0.88]), and diabetes (HR, 0.70 [CI, 0.54 to 0.92]). Pooled analyses of primary prevention cohort studies showed that compared with the lowest quantile, the highest quantile of adherence to a Mediterranean diet was associated with a reduction in total cancer mortality (risk ratio [RR], 0.86 [CI, 0.82 to 0.91]; 13 studies) and in the incidence of total (RR, 0.96 [CI, 0.95 to 0.97]; 3 studies) and colorectal (RR, 0.91 [CI, 0.84 to 0.98; 9 studies]) cancer. Of 3 secondary prevention studies reporting cardiovascular outcomes, 1 found a lower risk for recurrent myocardial infarction and cardiovascular death with the Mediterranean diet. There was inconsistent, minimal, or no evidence pertaining to any other outcome, including adherence, hypertension, cognitive function, kidney disease, rheumatoid arthritis, and quality of life. LIMITATIONS: Few trials; medium risk-of-bias ratings for many studies; low or insufficient strength of evidence for outcomes; heterogeneous diet definitions and components. CONCLUSION: Limited evidence suggests that a Mediterranean diet with no restriction on fat intake may reduce the incidence of cardiovascular events, breast cancer, and type 2 diabetes mellitus but may not affect all-cause mortality. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42015020262).
26906974 High prevalence of secondary factors for bone fragility in patients with a recent fracture 2016 In this study, we demonstrate a high prevalence of secondary factors in patients with a recent fracture independently of bone mineral density (BMD). Our results suggest that patients with a recent fracture should be screened for secondary factors for bone fragility regardless of BMD values. INTRODUCTION: Secondary factors for bone fragility are common in patients with osteoporosis who have sustained a fracture. The majority of fragility fractures occurs, however, in patients with osteopenia, and it is not known whether secondary factors may contribute to fracture risk in these patients or in those with normal BMD. METHODS: Prospective cohort study evaluating the prevalence of secondary factors for bone fragility in consecutive patients referred to our fracture liaison service from June 2012 to June 2014 after a recent fracture. RESULTS: Seven hundred nine patients were included, 201 (28 %) with osteoporosis, 391 (55 %) with osteopenia and 117 (17 %) with normal BMD. Mean age was 66.0 ± 9.8 years, 504 (73 %) were women and 390 (57 %) had one or more underlying secondary factor. Evaluation of clinical risk factors using fracture risk assessment tool (FRAX) identified 38 % of patients with ≥1 secondary factor including smoking (18 %), excessive alcohol use (12 %), glucocorticoid use (12 %) and rheumatoid arthritis (3 %). Laboratory investigations revealed chronic kidney disease in 13 %, monoclonal gammopathy also in 13 % and primary or secondary hyperparathyroidism in 1 and 6 %, respectively. Secondary factors for bone fragility were equally prevalent in patients with osteoporosis, osteopenia or normal BMD. CONCLUSIONS: Our findings demonstrate a high prevalence of secondary factors for bone fragility in patients who have sustained a recent fracture, independently of BMD. The significant number of documented factors, which were treatable, suggest that patients who sustained a fracture should be screened for secondary factors for bone fragility regardless of BMD values to optimise secondary fracture prevention.
25540922 Innate immunity alterations in idiopathic interstitial pneumonias and rheumatoid arthritis 2015 Feb BACKGROUND: This is a prospective cohort study elucidating innate immunity in idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) and RA-associated non specific interstitial pneumonia (RA-NSIP). METHODS: 23 IPF subjects, 9 COP subjects, 5 RA-UIP subjects, 8 RA-NSIP subjects were enrolled. 10 subjects were excluded. 19 healthy subjects served as controls. Blood and bronchoalveolar lavage (BAL) were obtained. Natural killer (NK) and NKT cells, NK cells apoptosis and the expression of triggering receptor expressed on myeloid cells type 1 (TREM-1) were assessed. Tumor necrosis factor-α (TNF-α) production was measured in cell cultures after stimulation with lipopolysaccharide endotoxin (LPS) and Pam3CysSK3, and in BAL. Surface expression of Toll-like receptors (TLR) 2 and 4 on peripheral blood monocytes (PBMC's) and circulating NK cells was also assessed. RESULTS: RA-NSIP had low blood NKs, marginally insignificant (p=0.07). These NKs poorly produced TNF-α after LPS stimulation. TLR's expression on NK cells was similar throughout disease groups and controls. PBMC's mainly from IPF patients exhibited low TNF-α production after LPS stimulation but not after Pam3CysSK3 stimulation, while TLR4 expression on PBMC's was found normal in all study groups. TLR2 expression on PBMC's was increased in IPF, but mainly in COP, RA-UIP and RA-NSIP (p=0.015). TREM-1 expression was significant on COP monocytes and on COP neutrophils versus controls. RA-NSIP monocytes also exhibited TREM-1 expression (p=0.07). Decreased TNF-α concentration in BAL was finally observed in IPF and RA-UIP. CONCLUSIONS: Innate immunity in the lungs and the peripheral circulation in IPF and RA-UIP are similar and more fibrotic than in RA-NSIP which is characterized by NK cell depletion and dysfunction. TREM-1 and TLR's likely affect patterns of inflammation in various interstitial lung diseases.
25504899 Insulin resistance in rheumatoid arthritis: disease-related indicators and associations wi 2015 Mar OBJECTIVE: Systemic inflammation and insulin resistance (IR) are linked, yet the determinants of IR and its impact on atherosclerosis in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and non-RA populations and investigate whether the associations of IR with measures of atherosclerosis differ between these groups. METHODS: IR was quantified using the homeostatic model assessment of IR (HOMA-IR), and was compared between RA patients and demographically matched non-RA controls. Differences in the associations between the HOMA-IR index and the Agatston coronary artery calcium (CAC) score, ultrasound-determined intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA), and focal plaque in the ICA/carotid bulb were compared according to RA status. RESULTS: Among the 195 RA patients and 198 controls studied, average HOMA-IR levels were higher in the RA group by 31%, and were consistently higher in the RA group regardless of stratification by demographic or cardiometabolic risk factors. While the HOMA-IR index was strongly and significantly associated with C-reactive protein (CRP) and interleukin-6 (IL-6) levels in the control group, the association was weaker in the RA group. Among RA patients, higher HOMA-IR levels were associated with rheumatoid factor (RF) seropositivity in men and women, and prednisone use in women only. Before adjustment, higher HOMA-IR levels were associated with all assessed measures of subclinical atherosclerosis in the control group only; associations were diminished and lost statistical significance after adjustment for cardiovascular risk factors. Among the RA patients, neither baseline nor average HOMA-IR levels were significantly associated with change in any of the atherosclerosis measures over an average of 3.2 years of followup. CONCLUSION: Although IR was higher in RA patients than in non-RA controls, higher levels may not independently impart additional risk of atherosclerosis.
25725773 Michaelis-Menten elimination kinetics of etanercept, rheumatoid arthritis biologics, after 2016 Aug Etanercept was approved by the Food and Drug Administration (FDA) in 2010 as a biologic agent for the treatment of rheumatoid arthritis (RA). The aim of the study was to investigate the pharmacokinetic properties of etanercept after intravenous and subcutaneous injection in rats. The plasma concentration of etanercept was determined using an enzyme-linked immunosorbent assay (ELISA). Intravenous and subcutaneous administration of 2 mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max] = 1.60 days, bioavailability [F] = 47.18 %) and slowly eliminated (half-life [t 1/2], 2.33 days after intravenous administration and 3.31 days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25 ± 14.37 and 48.56 ± 6.78 μg day/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max = 94.28 µg/day; K m = 10.88 µg/mL) was used to describe the pharmacokinetic profile of etanercept. Our results describe the pharmacokinetic profile of etanercept, and these results could be used for the development of etanercept biosimilars.
27086708 Tolerability of the COX-1/COX-2 inhibitor lornoxicam in the treatment of acute and rheumat 2016 Oct AIM: To assess the safety of lornoxicam with particular focus on gastrointestinal (GI) events. METHODS: Data on adverse drug reactions (ADRs) were pooled from 60 comparative studies of lornoxicam. RESULTS: A total of 6420 patients received lornoxicam, 1192 received placebo and 3770 received a comparator analgesic. ADRs were reported by 21% of lornoxicam-treated patients, with GI events the most frequent (14 vs 8% with placebo). Across 15 studies that compared lornoxicam (n = 1287) with another NSAID (n = 1010), there was a reduced risk of a GI ADR with lornoxicam (0.78 [95% CI: 0.64-0.96]; p = 0.017). CONCLUSION: Lornoxicam was well tolerated with the type of GI events observed consistent with the known safety profile of NSAIDs.
26923761 Extracellular citrullination inhibits the function of matrix associated TGF-β. 2016 Sep In inflammatory arthritis peptidyl arginine deiminase (PAD) enzymes can citrullinate arginine residues in extracellular matrix (ECM) proteins, such as collagens and fibronectin. This may lead to the generation of anti-citrullinated protein antibodies, important diagnostic markers in rheumatoid arthritis. In addition, the citrullination may directly affect protein function. Based on structural analysis, we found that most ECM-associated growth factors (GFs) have arginine residues in their receptor recognition sites. Thus, they are potential functional targets of extracellular citrullination. To examine this further, we focused on the citrullination of transforming growth factor-βs (TGF-β), well-known ECM-associated GFs. PAD-treatment of CHO-LTBP1 cell derived matrix, rich with TGF-β, decreased the level of TGF-β activity as detected by HaCaT and MLEC-PAI-1/Lu reporter cells. Additional experiments indicated that PAD-treatment inhibits the integrin-mediated TGF-β activation since PAD-treatment decreased the binding of integrin αVβ6 ectodomain as well as integrin-mediated spreading of MG-63 and HaCaT cells to β1-latency associated peptide (TGF-β1 LAP). The citrullination of the RGD site, an important integrin recognition motif, was confirmed by mass spectrometry. Furthermore, the citrullination of active TGF-β1 inhibited its binding to recombinant TGF-β receptor II, and prevented its ability to activate TGF-β signaling. Thus, extracellular PAD activity can affect the function of ECM-associated growth factors by different mechanisms. Importantly, the citrullination of both latent and active TGF-β has the potency to regulate the inflammatory process.
26362732 Th17 cytokines regulate osteoclastogenesis in rheumatoid arthritis. 2015 Nov This study determined the effect of type 17 helper T-cell (Th17) cytokines on osteoclastogenesis in rheumatoid arthritis (RA). The expression of IL-17 and receptor activator of NF-κB ligand (RANKL) was determined in synovial tissue, fibroblast-like synoviocytes (FLSs), and synovial fluids of RA patients using immunostaining and enzyme-linked immunosorbent assay. Th17 cytokine-induced RANKL expression was studied in RA FLS by using real-time PCR, luciferase activity assays, and Western blot analysis. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and Th17 cytokines, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-17-prestimulated FLS. There was significant correlation between RANKL and IL-17 levels in RA synovial fluid. IL-17, IL-21, and IL-22 increased the expression of Rankl mRNA in RA FLS, and the IL-17-induced RANKL expression decreased by the inhibition of Act1, tumor necrosis factor receptor-associated factor 6, NF-κB, and activator protein-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of exogenous RANKL. The osteoclastic effect was reduced by inhibition of tumor necrosis factor-α. Th17 cytokines have a dual effect on osteoclastogenesis in RA: direct induction of osteoclastogenesis from monocytes and up-regulation of RANKL production in RA FLS. This Th17 cytokine/RANKL axis could be a potential therapeutic target for bone destruction in RA.