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ID PMID Title PublicationDate abstract
29216915 Rheumatoid arthritis bone marrow environment supports Th17 response. 2017 Dec 8 BACKGROUND: Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and ultimately disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from "outside the joint" can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. It is believed that IL-17 is involved in pathogenesis of RA. However, little is known about the biology of this cytokine in BM. In the present study we investigated Th17-related cytokines in RA BM. METHODS: BM samples were obtained from RA and osteoarthritis (OA) patients during total hip replacement surgery. Levels of IL-17AF, IL-17AA, IL-17FF, IL-1β, IL-6, IL-23, TGF-β and CCL20 in BM plasma were determined by specific enzyme-linked immunosorbent assay tests. Percentage of IL-17-producing cells in BM was evaluated by flow cytometry. The effect of IL-15 stimulation on IL-17 production by BM mononuclear cells was examined in vitro. RESULTS: Increased levels of IL-17AF were observed in BM plasma of RA patients in comparison to OA patients. Increased concentrations of IL-1β, IL-6 and CCL20 were observed in RA compared to OA BM plasma. Concordant with these findings, significantly increased percentages of CD3(+)CD4(+)IL-17(+) and CD3(+)CD4(+)IL-17(+)IFN-γ(+) cells were present in RA BM in comparison to OA BM samples. Finally, abundant in RA BM, IL-15 increased IL-17 production by cultured BM mononuclear cells. CONCLUSIONS: In the course of RA, the BM microenvironment can promote the development of Th17 cell responses and overproduction of IL-17AF that may lead to increased inflammation and tissue destruction in RA BM.
29134891 Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgrou 2018 Jul OBJECTIVES: To evaluate efficacy/safety of baricitinib for rheumatoid arthritis (RA) in Japanese subpopulations from four phase 3 studies, and assess whether results in these subpopulations are consistent with the overall study populations. METHODS: Subgroup analyses (394 patients) of four phase 3 randomized controlled trials: RA-BEGIN [no or limited treatment with disease-modifying antirheumatic drugs (DMARDs)], RA-BEAM [inadequate response (IR) to methotrexate], RA-BUILD [IR to conventional synthetic DMARDs (csDMARDs)], and RA-BEACON (IR to tumor necrosis factor inhibitors receiving csDMARDs). RESULTS: For American College of Rheumatology 20% improvement (ACR20) response rate, Japanese patients receiving baricitinib 4-mg showed similar improvement compared to methotrexate at Week 24 (72 versus 69%; RA-BEGIN), and greater improvement compared with placebo at Week 12 (67 versus 34%; RA-BEAM). Japanese patients receiving baricitinib 4-mg also showed greater improvement compared with placebo at Week 12 in RA-BUILD and RA-BEACON. Across all studies, baricitinib was well-tolerated, with no deaths and one malignancy. In RA-BEGIN and RA-BEAM, herpes zoster rates were higher for Japanese patients than for overall populations; all events were mild/moderate. CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations. Baricitinib appears to be similarly effective in Japanese patients.
28118524 A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for 2017 May OBJECTIVE: Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci. METHODS: The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population. RESULTS: Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10(-16) ), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10(-5) ) and with seropositive RA (P = 1.48 × 10(-6) ) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci. CONCLUSION: This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the pathophysiology of RA.
28028156 Patients' preferences and economic considerations play an important role in treatment deci 2017 Jan OBJECTIVE: To evaluate to what extent rheumatologists consider economic aspects and patients' preferences when choosing drug treatments in patients with active RA. METHODS: In a discrete choice experiment, rheumatologists were asked to choose between two unlabelled drug treatment options for a hypothetical RA patient with moderate disease activity who failed two synthetic DMARDs. Attributes and levels of drug treatments were selected based on existing literature, rheumatologists' opinion and expert consensus. This resulted in five attributes each described by three levels: efficacy (level of improvement and achieved state on DAS28), safety (probability of a serious adverse event), patients' preference (level of agreement), annual medication costs and cost-effectiveness (incremental cost-effectiveness ratio). An efficient experimental design generated 14 treatment choices and a random parameter logit model estimated the relative importance of attributes. RESULTS: Sixty-three rheumatologists from the Netherlands contributed to the analysis; 44% were female and mean (sd) age was 49 (8) years. Drug efficacy had the strongest relative contribution to the drug choice (44%) followed by medication costs (24%), patients' preference (17%) and cost-effectiveness (14%). Patients' preferences were most relevant when patients disliked a proposed treatment. The risk of serious but uncommon or rare side effects only played a minor role in the treatment choice (1%). CONCLUSION: In addition to drug efficacy, rheumatologists account for economic aspects and for patients' preferences when deciding on drugs. Decisions are more influenced by absolute costs than relative cost-effectiveness and by patients' disliking as opposed to favouring the treatment.
28423031 Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutriti 2017 This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.
28461107 Tofacitinib attenuates arthritis manifestations and reduces the pathogenic CD4 T cells in 2017 Nov Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leukocyte infiltration in affected joints. Tofacitinib is new agent, a selective inhibitor of Janus kinase (JAK) signaling pathways mediated by JAK1 and JAK3 and inhibits the key transcription factors STAT1 and STAT3. We investigated the action mechanisms of tofacitinib in rats with adjuvant-induced-arthritis (AIA). AIA-rats were treated orally with tofacitinib or with methotrexate. Arthritis severity and serum C-reactive protein (CRP) levels were evaluated, splenic cells were examined by flow cytometry and cytokines were analyzed by real-time PCR. Tofacitinib markedly reduced the clinical status of treated rats in comparison to control group. Reduced joints inflammation and down-regulated serum CRP levels reflected the clinical manifestations of the treated rats. Tofacitinib down-regulated significantly the frequency of CD4(+)IFN-γ(+) T cells and reduced IL-1β mRNA expression levels in the spleen of the treated rats. These results show that tofacitinib attenuated arthritis severity, modified splenic populations and cytokine imbalance.
28314444 PDK1 promotes the inflammatory progress of fibroblast-like synoviocytes by phosphorylating 2017 May This study investigated the role of PDK1 in inflammatory response which is initiated by TNF-α and analyzed the association between PDK1 and RSK2. TNF-α were added into MH7A cells to induce inflammation condition. Through overexpressing or suppressing PDK1 in MH7A cells, the role of PDK1 in cell invasiveness and inflammatory factors was determined. Levels of MMPs protein and inflammatory cytokines were assessed with PDK1 siRNA and TNF-α treatment. Inhibition of RSK2 was used to investigate the function of RSK2 on PDK1-induced inflammation. The phosphorylation of RSK2 was detected when PDK1 was inhibited. Luciferase reporter assay was performed to detect the transcriptional activity of NF-κB. We found highly expressed PDK1 could promote cell invasion and secretion of IL-1β and IL-6 in MH7A cells. Inhibition of RSK2 reduced the PDK1-induced cell invasion and cytokines secretion in MH7A cells. In response to TNF-α, PDK1 could phosphorylate RSK2 and activated RSK2, then promoting the activation of NF-κB. This may be a possible therapeutic option of rheumatoid arthritis.
28990193 Antimicrobial peptides as a possible interlink between periodontal diseases and its risk f 2018 Apr Antimicrobial peptides (AMPs) play a critical role in controlling innate and acquired immune responses. Local dysregulation of AMP is implicated in the pathogenesis of periodontal diseases as a response to periodontal pathogen challenge. Changes in AMP expression also characterize tobacco smoking, diabetes mellitus, obesity and rheumatoid arthritis, which are established risk factors of periodontal diseases, suggesting AMP may act as putative mechanistic links between these. The aim was to evaluate and summarize critically the current evidence pertaining to interrelationships between AMPs, periodontal diseases and selected periodontal disease risk factors. General and theme specific keywords were used to search the PUBMED database for studies relevant to AMP, periodontal diseases, smoking, diabetes mellitus, obesity and rheumatoid arthritis and critically reviewed. A total of 131 abstracts and 119 full text articles were screened for relevance; 13 studies were selected for inclusion after critical review. Local AMP dysregulation characteristic to periodontal diseases appears to occur within a broader landscape of complex systemic immune perturbations independently induced by smoking, metabolic and rheumatoid disease. The nature of these interactions and mechanistic pathways involved are inadequately understood. AMPs could be possible mechanistic interlinks between periodontal diseases and its risk factors. However, such evidence is very limited and more in vivo and in vitro studies are necessary to clarify the nature of such relationships. A greater understanding of AMPs as shared mediators is essential for unraveling their value as therapeutic or biomarker candidates.
28703549 [Anti-IL-6 : new therapeutic trends]. 2017 Jan 11 The anti-IL-6 tocilizumab is a recognized treatment in rheumatoid arthritis and in systemic juvenile idiopathic arthritis. Almost ten years after its first use, there is more information about its security profile and its indication should be extended to other systemic inflammatory diseases, such as the giant cell arteritis. New molecules targetting the IL-6 pathway are under validation : sarilumab, sirukumab and olokizumab. Here is a brief state of the future outlook and trends of this therapeutic class.
29222254 Chronic neutropenia in LGL leukemia and rheumatoid arthritis. 2017 Dec 8 This section reviews the diagnostic criteria and pathogenesis of large granular lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of the mechanisms of neutropenia in these disorders is discussed. Finally, treatment indications and therapeutic recommendations are outlined.
28440680 Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: 2018 Jan OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of long-term (64 weeks; 52-week extension of a 12-week study) baricitinib treatment in Japanese patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients (N = 145) with active RA were randomized to placebo, 1mg, 2mg, 4mg, or 8mg baricitinib for the first 12 weeks. During the 52-week extension period, patients on 4mg or 8mg baricitinib remained on the same dose and all other patients were re-randomized to 4mg or 8mg baricitinib. Most patients on 8mg baricitinib were switched to 4mg by week 64 (protocol amendment); data analysis was based on the treatment group at the beginning of the extension period. RESULTS: Increases in the American College of Rheumatology (ACR) response rates (ACR20, ACR50, and ACR70) observed during the first 12 weeks were maintained during the extension period, accompanied by improvements in ACR core components. At week 64, a large proportion of patients (>40%) had low disease activity. Most treatment-related adverse events were mild or moderate; herpes zoster was the most common reason (11/27 patients) for discontinuation. CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy. Clinicaltrials.gov NCT01469013; Funding: Eli Lilly and Incyte.
28222760 TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopat 2017 Feb 21 BACKGROUND: The aim of the study was to determine whether polymorphisms in toll-like receptor 4 (TLR4) confer susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population. METHODS: Genotyping for six well studied polymorphisms (rs4986790, rs4986791, rs10759932, rs41426344, rs11536889 and rs7873784) in TLR4 gene were conducted in 1074 unrelated patients with RA and 1692 healthy control subjects, as well as in 217 unrelated patients with JIA and 378 healthy control subjects using direct sequencing technique. Comparisons between cases and controls in alleles, genotypes and haplotypes were carried out using Fisher's exact test. RESULTS: Significant genetic associations were detected between the 3'UTR rs41426344C and RA (p < 0.001, p (adj) < 0.001, OR = 2.24) and JIA (p < 0.001, p (adj) < 0.001, OR = 2.05). In addition, rs4986790G was found to be significantly associated with the susceptibility for RA (p = 0.005, p (adj) = 0.03, OR = 3.43), but not for JIA (p = 0.06, p (adj) = 0.36, OR = 2.65). Furthermore, significant increasing in the distributions of haplotypes H4 and H10 in RA (H4: p = 0.001, OR = 1.13; H10: p = 0.001, OR = 1.15) and JIA (H4: p = 0.04, OR = 2.06; H10: p = 0.02, OR = 2.47) were also found. Moreover, the frequency of rs41426344C significantly increased in RF-positive and anti-CCP positive subjects both in RA (RF(+): p <0.0001, OR = 2.33; anti-CCP(+): p =0.008, OR = 2.79) and JIA (RF(+): p =0.02, OR = 2.91; anti-CCP(+): p = 0.02, OR = 2.78). CONCLUSIONS: Our study suggested that rs41426344 and rs4986790 of TLR4 might contribute to RA, and rs41426344 might contribute to JIA pathogenesis in central south Chinese Han population.
28213566 A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal ant 2017 Jun OBJECTIVES: Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. METHODS: In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28-CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24). RESULTS: 326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012-June 2013). Mavrilimumab treatment significantly reduced DAS28-CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: -1.90 (0.14), 100 mg: -1.64 (0.13), 30 mg: -1.37 (0.14), placebo: -0.68 (0.14); p<0.001; all dosages compared with placebo).Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified. CONCLUSIONS: Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential. TRIAL REGISTRATION NUMBER: NCT01706926; results.
28728599 A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inf 2017 Jul 20 BACKGROUND: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA®, CinnaGen, Iran) to the innovator product (Humira®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA). METHODS: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA® or Humira® every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety. RESULTS: Patients who were randomized to CinnoRA® or Humira® arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA® group was non-inferior to the Humira® group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA® and Humira® groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant. CONCLUSION: CinnoRA® was shown to be non-inferior to Humira® in terms of efficacy at week 24 with a comparable safety profile to the reference product. TRIAL REGISTRATION: IRCT.ir, IRCT2015030321315N1 . Registered on 5 April 2015.
28870177 Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely contr 2017 Sep 5 BACKGROUND: Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF). METHODS: This study will be an 8-week double-blinded, randomized, placebo-controlled clinical trial conducted at Guang'anmen Hospital in Beijing, China, and 168 patients with moderately active RA will be randomly assigned with a 1:1 ratio to apply a topical gel preparation containing TwHF or placebo. The primary outcome variable will be the proportion of subjects, by study group, to achieve a 20% improvement in the American College of Rheumatology criteria (ACR20) by week 8. Secondary outcome measures to be assessed at weeks 4 or 8 will include: measurement of ACR20 response rate at week 4, ACR50 response rate, the changes in DAS28 score, and joint synovitis classification assessment monitored by musculoskeletal ultrasound. Safety evaluations conducted at weeks 4, 8 and 12 will be based on spontaneous complaints by the study subjects, but special emphasis will be focused on cutaneous allergy and alterations of menstruation in premenopausal female participants. Statistical analyses will be performed using the intention to treat analysis data set. DISCUSSION: This proposed clinical trail is designed to evaluate the efficacy and safety of CET based on a single topically-applied agent in a relatively large patient population with RA. This study protocol gives a detailed description of the usage and dosage of the topical compound TwHF gel and the methodology of this study. In addition, it is hoped that the outcomes of this study will be viewed as supporting the generalizability of CET in the setting of inflammatory rheumatic diseases. The results of this study are expected to have important public health implications for Asian RA patients that currently utilize CET as a complimentary treatment. TRIAL REGISTRATION: Clinical trial gov Identifier: NCT02818361 . Registrated on Jun. 15, 2016.
28283512 Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature revi 2017 Jun OBJECTIVES: To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained. RESULTS: The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or 'spacing' was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B). CONCLUSIONS: This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.
28601838 Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in 2017 Jun 10 BACKGROUND: Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). METHODS: This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders. RESULTS: The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline. CONCLUSIONS: Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs.
28075587 Design and Synthesis of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase 2017 Feb 9 We report the synthesis of a series of hybrid compounds incorporating 6- and 7-substituted coumarins (carbonic anhydrase, CA inhibitors) derivatized with clinically used NSAIDs (indomethacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase inhibitors) as agents for the management of rheumatoid arthritis (RA). Most compounds were effective in inhibiting the RA overexpressed hCA IX and XII, with K(I) values in the low nanomolar-subnanomolar ranges. The antihyperalgesic activity of such compounds was assessed by means of the paw-pressure and incapacitance tests using an in vivo RA model. Among all tested compounds, the 7-coumarine hybrid with ibuprofen showed potent and persistent antihyperalgesic effect up to 60 min after administration.
28039554 Serum level of DNase1l3 in patients with dermatomyositis/polymyositis, systemic lupus eryt 2017 Nov DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study. Serum levels of DNase1l3 were quantified by enzyme-linked immunosorbent assay. DNASE1L3 activity in serum was estimated by the capability of serum to digest nucleosomal DNA. Clinical, biochemical, serological and other markers of disease activity (CRP, ESR, C3, C4, anti-Jo-1 and anti-dsDNA, etc.) were measured by standard laboratory procedure. We found a decrease in DNase1l3 level in the DM/PM and SLE patients, resulting in the reduction in serum activity to digest nucleosome DNA. In contrast, the level and activity of DNase1l3 remained unchanged in the RA patients. The DNase1l3 level was relatively lower in the DM/PM patients with anti-Jo-1 antibody and interstitial lung disease, and in the SLE patients with SLE disease activity index higher than 6, renal involvement and anti-dsDNA antibody. DNase1l3 level negatively correlated with CRP and IgG in the PM/DM patients and correlated with ESR in the SLE patients. We found a significant reduction in serum DNase1l3 level in DM/PM and SLE, which may associate with clinic features and disease activity.
27774648 Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of 2017 Jan OBJECTIVES: The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed. KEY FINDINGS: Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOXs) and arachidonic acid (AA). Despite the presence of significant merits, the use of these bioactives has several demerits such as poor bioavailability as a function of low aqueous solubility and higher first-pass metabolism upon oral administration. The impact of nano/submicromedicine in the delivery of these bioactives against RA has gained wider attention owing to bioavailability enhancement, higher stability and better efficacy. CONCLUSION: Phytoconstituents possess immense potential in RA pharmacotherapy, but the obstacles for their effective delivery can be overcome using nano/submicrocarrier-based drug delivery technologies, which maximize the efficacy of these herbal antirheumatic drugs without any systemic adverse effects.