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1.
Introduction
Literature data suggest that sleep disturbances are prevalent among patients with ankylosing spondylitis (AS) and have a close correlation with pain. Other studies indicate that sleep disturbances are constantly accompanied by depression and anxiety in AS, but their interrelations are poorly understood. This study was designed to evaluate sleep disturbances and their association with demographic variables, pain, disease-specific variables, functional status, covering depression and anxiety in AS patients.Methods
The 314 patients with AS and age- and sex-matched controls took part in the study, completed a battery of questionnaires, and participated in long-term follow-up. Blood samples were taken to measure C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR). The association among sleep, pain, disease activity, functional status, depression, and anxiety were assessed by using Pearson/Spearman correlations and multiple regression analysis.Results
The Pittsburgh Sleep Quality Index (PSQI) score of the Chinese version was significantly higher in the AS group than in the control group (P = 0.020). Of the 314 patients with AS, 184 (58.6%) had a high risk for sleep disturbances. The PSQI score was associated with age, years of education, ESR, CRP, overall assessment of health, pain, morning stiffness, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), depression, and anxiety (all P < 0.001), but were not associated with disease duration, fingertip-to-floor distance, and Bath Ankylosing Spondylitis Metrology Index (BASMI) (P > 0.05). In hierarchic multiple regression analysis, the medical and psychological variables contributed significantly to the variance in sleep-disturbances scores, adding an additional 23.9% to the overall R2 beyond that accounted for by demographic variables (R-square, 8.5%), resulting in a final R2of 42.6%. Multiple stepwise regression analysis revealed that anxiety was the maximal statistical contribution in predicting sleep disturbances (standardized coefficients, 0.287).Conclusions
The prevalence of sleep disturbances in AS patients is higher than it is generally thought to be. Depression, anxiety, nocturnal pain, and total back pain are the major contributors of sleep disturbances in AS. 相似文献2.
Carla GS Saad Ana CM Ribeiro Julio CB Moraes Liliam Takayama Celio R Goncalves Marcelo B Rodrigues Ricardo M de Oliveira Clovis A Silva Eloisa Bonfa Rosa MR Pereira 《Arthritis research & therapy》2012,14(5):R216
Introduction
Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.Methods
Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.Results
At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.Conclusions
Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy. 相似文献3.
Lucy Law Jeanette Beckman Rehnman Anna Deminger Eva Klingberg Lennart T. H. Jacobsson Helena Forsblad-d’Elia 《Arthritis research & therapy》2018,20(1):284
Background
Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex.Methods
A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient’s SF-36 results were compared with those of five age-matched and sex-matched persons (n?=?1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables.Results
A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p?<?0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00–5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16–2.37), higher BASFI (OR 1.98, 95% CI 1.46–2.70) and ASDAS ≥?2.1 (OR 3.32, 95% CI 1.45–7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34–6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06–13.19) and ASDAS ≥?2.1 (OR 2.97, 95% CI 1.41–6.25) with worse MCS. Some differences between sexes were observed in the results.Conclusions
The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved.Trial registration
ClinicalTrials.gov, NCT00858819. Registered on 9 March 2009. Last updated on 28 May 2015.4.
Introduction
The arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic axSpA and ankylosing spondylitis. Following its validation in rheumatoid and psoriatic arthritis, we aimed to assess psychometric properties of WPS in adult-onset active axSpA in this analysis.Methods
Psychometric properties were assessed using data from the RAPID-axSpA trial () in which researchers investigated certolizumab pegol efficacy and safety in axSpA. WPS was completed at baseline and every 4 weeks until week 24. Validity was evaluated at study baseline via known-groups defined by the first and third quartile cutoffs of patient scores to Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain, Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form 36 health survey (SF-36) and Ankylosing Spondylitis Quality of Life Scale (ASQoL). Responsiveness and reliability were assessed by comparing WPS mean changes in ASAS 20% improvement criteria (ASAS20), BASDAI50, ASDAS clinically important improvement/major improvement (CII/MI) and BASFI minimum clinically important difference (MCID) responders versus nonresponders at week 12. All comparisons were conducted on observed cases in the randomized set using a nonparametric bootstrap-t method. NCT01087762Results
The results confirmed the psychometric properties of WPS. AxSpA patients with a worse health state had significantly more days of household work lost, household work with reduced productivity, social activities missed and outside help hired, as well as a higher interference rate of arthritis, than patients with a better health state. Similarly, employed patients with a worse health state had significantly more work days lost or with productivity reduced, and a higher interference of arthritis on work productivity. Similar findings were also observed in the nonradiographic (nr) axSpA and AS subpopulations. The WPS was responsive to clinical changes, with responders reporting larger improvements at week 12 in WPS scores versus nonresponders. Effect sizes in responders were generally moderate to large (standardized response mean >0.5).Conclusions
These analyses demonstrate that WPS is a valid, responsive and reliable instrument for the measurement of productivity within and outside the home in adult-onset axSpA, as well as the in subpopulations of AS and nr-axSpA.Electronic supplementary material
The online version of this article (doi:10.1186/ar4680) contains supplementary material, which is available to authorized users. 相似文献5.
Anja Wei? In-Ho Song Hildrun Haibel Joachim Listing Joachim Sieper 《Arthritis research & therapy》2014,16(1):R35
Introduction
The aim of this study was to investigate the influence of symptom duration on treatment response and on the correlation between improvements in patient reported outcomes (PRO) and objective inflammation in patients with axial spondylarthritis (SpA) treated with etanercept (ETA) or adalimumab (ADA).Methods
Data from 112 patients with axial SpA originally enrolled in two randomized controlled clinical trials were pooled and analyzed after one year of treatment with ETA (n = 66) or ADA (n = 46). Patients with <4 years and ≥4 years of disease were compared for improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP) and magnetic resonance imaging (MRI) score for sacroiliac joints (SIJ).Results
Patients with <4 years of disease showed a significantly better improvement than longer diseased patients in BASDAI (3.2 (95% confidence interval (CI): 2.7 to 3.7) vs. 1.7 (1.1 to 2.2)), BASFI, BASMI and ASDAS (1.6 (1.4 to 1.8) vs. 0.9 (0.7 to 1.1)). The change in BASDAI showed a significant correlation with the change in SIJ score (Spearman’s rank correlation coefficient (rho) = 0.37, P = 0.01) and the change in CRP (rho = 0.45, P = 0.001) in patients with <4 years of disease. For long diseased patients this correlation was poor and did not achieve statistical significance (rho = 0.13, P = 0.46; rho = 0.22, P = 0.13 respectively).Conclusion
The low correlation between change of PROs and change of objective signs of inflammation seen in axial SpA patients with longer symptom duration treated with tumor necrosis factor-blocker seems to indicate that inflammation is not the only cause of the patients’ symptoms, while inflammation seems to be the major cause in short diseased patients.Trial registration
Clinical Trials.gov NCT00844142 (Trial 1); NCT00235105 (Trial 2) 相似文献6.
Dinny Wallis Arundip Asaduzzaman Michael Weisman Nigil Haroon Ammepa Anton Dermot McGovern Stephan Targan Robert Inman 《Arthritis research & therapy》2013,15(5):R166
Introduction
Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) share genetic and clinical features. IBD is associated with the presence of antibodies to a variety of commensal microorganisms including anti-Saccharomyces cerevesiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti-I2 (associated with anti-Pseudomonas activity), anti-Eschericia coli outer membrane porin C (anti-OmpC) and anti-flagellin antibodies (anti-CBir1). Subclinical intestinal inflammation may be present in up to 65% of patients with AS. This study evaluated the presence of antimicrobial antibodies in patients with AS alone, patients with AS and concomitant IBD (AS-IBD) and a control group of patients with mechanical back pain (MBP).Methods
Sera were tested by ELISA for ASCA IgG and IgA, anti-OmpC, anti-CBir1 and ANCA in 76 patients with AS alone, 77 patients with AS-IBD and 48 patients with MBP. Antibody positivity rates, median quantitative antibody levels and the proportion of patients with antibody levels in the 4th quartile of a normal distribution were compared between the three groups of patients.Results
Patients with AS alone demonstrated higher anti-CBir1 antibody positivity rates and median antibody levels than MBP patients. Anti-CBir1 positivity in AS was associated with elevation of acute phase reactants. AS-IBD patients demonstrated elevated responses when compared to AS alone for ASCA, anti-OmpC and anti-CBir1. Quartile analysis confirmed the findings.Conclusions
These data suggest that adaptive immune responses to microbial antigens occur in AS patients without clinical IBD and support the theory of mucosal dysregulation as a mechanism underlying the pathophysiology of AS. 相似文献7.
Introduction
In this study, we evaluated the clinical relevance of serum drug levels and antidrug antibodies (ADAbs) with regard to response to treatment, as well as to relapse upon treatment discontinuation, in peripheral spondyloarthritis (pSpA) patients treated with adalimumab.Methods
The study included 26 pSpA patients treated with adalimumab for either 12 weeks (n = 12) or 24 weeks (n = 14) in a randomized controlled trial. Patients achieving inactive disease measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) at the end of the treatment period were classified as responders. Clinical characteristics, serum trough adalimumab levels and ADAbs were assessed at the end of the treatment period and at follow-up (upon relapse or, in absence of relapse, at 16 weeks after discontinuation).Results
Serum adalimumab levels measured 2 weeks after the last adalimumab administration ranged from <0.002 to 23.0 μg/ml, with a median of 11.5 μg/ml. These levels were associated with neither response to treatment or disease activity measurements at the end of treatment nor with the occurrence of relapse and time to relapse after discontinuation of treatment. Antiadalimumab ADAbs were present in 23% of the patients at end of treatment and in 35% at follow-up after treatment discontinuation, indicating that ADAbs were masked by the presence of the drug in some patients. However, ADAbs at the end of treatment and at follow-up were not different between responders and nonresponders and were not associated with relapse upon discontinuation of treatment.Conclusions
There is no clear association between adalimumab serum levels or antiadalimumab ADAbs with clinical response to treatment or with relapse upon treatment discontinuation in pSpA.Trial registration
Netherlands Trial Register ID: NTR1806 (registered 7 May 2009) 相似文献8.
Inês P. Perpétuo Rita Raposeiro Joana Caetano-Lopes Elsa Vieira-Sousa Raquel Campanilho-Marques Cristina Ponte Helena Canh?o Mari Ainola Jo?o E. Fonseca 《PloS one》2015,10(12)
Introduction
Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients.Methods
13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed.Results
RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline.Conclusion
In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli. 相似文献9.
Young Bin Joo So-Young Bang Tae-Hwan Kim Seung-Cheol Shim Seunghun Lee Kyung Bin Joo Jong Heon Kim Hye Joon Min Proton Rahman Robert D. Inman 《PloS one》2014,9(8)
Background and Object
Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.Methods
A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.Results
We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74×10−4) and rs1235192 [OR 1.92, p = 1.17×10−3]) adjusted by covariates.Conclusion
This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS. 相似文献10.
Wei JC Yen JH Juo SH Chen WC Wang YS Chiu YC Hsieh TJ Guo YC Huang CH Wong RH Wang HP Tsai KL Wu YC Chang HW Hsi E Chang WP Chang WC 《PloS one》2011,6(6):e20426
Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility. We carried out a case-control study to determine whether the genetic polymorphisms of ORAI1 gene, a major component of store-operated calcium channels that involved the regulation of immune system, is a susceptibility factor to AS in a Taiwanese population. We enrolled 361 AS patients fulfilled the modified New York criteria and 379 controls from community. Five tagging single nucleotides polymorphisms (tSNPs) at ORAI1 were selected from the data of Han Chinese population in HapMap project. Clinical statuses of AS were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Index (BAS-G). Our results indicated that subjects carrying the minor allele homozygote (CC) of the promoter SNP rs12313273 or TT homozygote of the SNP rs7135617 had an increased risk of HLA-B27 positive AS. The minor allele C of 3′UTR SNP rs712853 exerted a protective effect to HLA-B27 positive AS. Furthermore, the rs12313273/rs7135617 pairwise allele analysis found that C-G (OR 1.69, 95% CI 1.27, 2.25; p = 0.0003) and T-T (OR 1.75, 95% CI 1.36, 2.27; p<0.0001) haplotypes had a significantly association with the risk of HLA-B27-positive AS in comparison with the T-G carriers. This is the first study that indicate haplotypes of ORAI1 (rs12313273 and rs7135617) are associated with the risk of HLA-B27 positive AS. 相似文献
11.
Tue W Kragstrup Babak Jalilian Malene Hvid Anders Kj?rgaard René ?stg?rd Berit Schi?ttz-Christensen Anne G Jurik William H Robinson Thomas Vorup-Jensen Bent Deleuran 《Arthritis research & therapy》2014,16(1):R42
Introduction
Spondyloarthritis (SpA) comprises a group of diseases often associated with HLA-B27 and characterized by inflammation of the entheses and joints of the axial skeleton. The inflammatory process in SpA is presumably driven by innate immune cells but is still poorly understood. Thus, new tools for monitoring and treating inflammation are needed. The family of CD18 integrins is pivotal in guiding leukocytes to sites of inflammation, and CD18 hypomorphic mice develop a disease resembling SpA. Previously, we demonstrated that altered soluble CD18 (sCD18) complexes in the blood and synovial fluid of patients with arthritis have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity.Methods
Plasma levels of sCD18 in a study population with 84 patients with SpA and matched healthy controls were analyzed with a time-resolved immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synoviocytes (FLSs) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMCs) was studied with flow cytometry and TRIFMA.Results
Plasma levels of sCD18 were decreased in patients with SpA compared with healthy volunteers (P <0.001), and the lowest levels were in the HLA-B27-positive subgroup (P <0.05). In a multiple regression model, the sCD18 levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P <0.05), the level of morning stiffness (P <0.05), the Bath Ankylosing Spondilitis Metrology Index (P <0.05), the physician global assessment score (P <0.01), and the sacroiliac magnetic resonance imaging activity score (P <0.05). The mechanisms for these changes could be simulated in vitro. First, sCD18 in plasma adhered to inflammation-induced intercellular adhesion molecule 1 (ICAM-1) on endothelial cells and FLS, indicating increased consumption. Second, CD18 shedding from SpA PBMCs correlated inversely with the BASDAI (P <0.05), suggesting insufficient generation. CD18 was shed primarily from intermediate CD14++ CD16+ monocytes, supporting the view that alterations in innate immunity can regulate the inflammatory processes in SpA.Conclusions
Taken together, the failure of patients with SpA to maintain adequate sCD18 levels may reflect insufficient CD18 shedding from monocytes to counterbalance the capture of sCD18 complexes to inflammation-induced ICAM-1. This could increase the availability of ICAM-1 molecules on the endothelium and in the synovium, facilitating leukocyte migration to the entheses and joints and aggregating disease activity. 相似文献12.
Maxime Dougados Emily Wood Bernard Combe Thierry Schaeverbeke Corinne Miceli-Richard Francis Berenbaum Nandan Koppiker Arnaud Dubanchet Isabelle Logeart 《Arthritis research & therapy》2014,16(6)
Introduction
In clinical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly discontinued after response to biologic therapy is achieved in patients with axial spondyloarthritis (axSpA), but the impact of NSAID discontinuation has not been assessed in prospective controlled trials. The aim of the SPARSE study was to evaluate the effects of the anti-tumor necrosis factor agent etanercept on NSAID intake and conventional clinical outcomes in axSpA patients.Methods
In the double-blind, placebo-controlled period, patients with active (mini Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4) axSpA despite optimal NSAID intake were randomized to receive etanercept 50 mg or placebo once weekly for 8 weeks. All patients were advised to taper/discontinue their NSAID intake during the treatment period. NSAID intake was self-reported by diary and Assessment of SpondyloArthritis International Society (ASAS)-NSAID scores calculated based on ASAS recommendations. The primary endpoint was change from baseline to week 8 in ASAS-NSAID score (analysis of covariance).Results
In 90 randomized patients at baseline, mean age (standard deviation) was 38.9 (11.8) years; disease duration, 5.7 (8.1) years; 59/90 (66%) were human leukocyte antigen-B27 positive; 51/90 (57%) had radiographic sacroiliitis; and 45/90 (50%) were magnetic resonance imaging sacroiliitis-positive. Mean ASAS-NSAID scores were similar between etanercept and placebo groups at baseline (98.2 (39.0) versus 93.0 (23.4)), as were BASDAI (6.0 (1.7) versus 5.9 (1.5)), and Bath Ankylosing Spondylitis Functional Index (5.2 (2.1) versus 5.1 (2.2)). Mean changes (SE) in ASAS-NSAID score from baseline to week 8 were –63.9 (6.1) and –36.6 (5.9) in the etanercept and placebo groups (between-group difference, –27.3; P = 0.002). Significantly higher proportions of patients receiving etanercept versus placebo had an ASAS-NSAID score <10 (46% versus 17%; P = 0.008) and ASAS-NSAID score of 0 (41% versus 14%; P = 0.013) at this time point. Significantly more patients in the etanercept versus placebo group achieved BASDAI50 (39% versus 18%; P = 0.032) and ASAS40 (44% versus 21%; P = 0.028) at week 8.Conclusions
In patients with axSpA, etanercept was associated with clinically relevant NSAID-sparing effects in addition to significant improvements in conventional clinical outcomes.Trial registration
ClinicalTrials.gov . Registered 16 February 2011. NCT01298531Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0481-5) contains supplementary material, which is available to authorized users. 相似文献13.
Xenofon Baraliakos Hildrun Haibel Claudia Fritz Joachim Listing Frank Heldmann Juergen Braun Joachim Sieper 《Arthritis research & therapy》2013,15(3):R67
Introduction
Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y).Methods
Overall, 26 patients with active AS were initially treated with etanercept 2 × 25 mg s.c./week with no concomitant disease modifying anti-rheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. The primary outcome was the proportion of patients in the Spondyloarthritis International Society (ASAS) partial remission at seven years. AS disease activity scores (ASDAS) for status and improvement were compared to conventional outcome measures.Results
Overall, 21/26 patients (81%) completed two years of treatment and 16/26 patients (62%) completed seven years. In the completer analysis, 31% patients were in ASAS partial remission at seven years, while 44% patients showed an ASDAS inactive disease status. Mean Bath AS activity index (BASDAI) scores, which were elevated at baseline (6.3 ± 0.9), showed constant improvement and remained low: 3.1 ± 2.5 at two years and 2.5 ± 2.2 at seven years, while ASDAS also improved (3.9 ± 0.7 at baseline, 1.8 ± 0.9 at two years, 1.6 ± 0.8 at seven years), all P <0.001. From the 10 dropouts, only 5 patients discontinued treatment due to adverse events. Patients who completed the study had lower baseline Bath AS function index (BASFI) scores vs. patients who discontinued. No other clinical parameter at baseline could predict any long-term outcome.Conclusions
This study confirms the clinical efficacy and safety of etanercept in patients with active AS over seven years of continuous treatment. After seven years, more than half of the initially treated patients remained on anti-TNF therapy, and one-third were in partial remission.Trial Registration
ClinicalTrials.gov: NCT01289743相似文献14.
Incidence and predictors of morphometric vertebral fractures in patients with ankylosing spondylitis
Kwi Young Kang In Je Kim Seung Min Jung Seung-Ki Kwok Ji Hyeon Ju Kyung-Su Park Yeon Sik Hong Sung-Hwan Park 《Arthritis research & therapy》2014,16(3):R124
Introduction
Ankylosing spondylitis (AS) is associated with an increased incidence of vertebral fractures (VFs); however the actual incidence and predictors of morphometric VFs are unknown. The present study examined the incidence and predictors of new VFs in a large AS cohort.Methods
In total, 298 AS patients who fulfilled the modified New York criteria were enrolled and spinal radiographs were evaluated biennially. Clinical and laboratory data and radiographic progression were assessed according to the Bath AS Disease Activity Index, erythrocyte sedimentation rate, C-reactive protein (CRP), and the Stoke AS spine score (SASSS). VF was defined according to the Genant criteria. The incidence of VFs at 2 and 4 years was evaluated using the Kaplan-Meier method. The age-specific standardized prevalence ratio (SPR) for AS patients in comparison with the general population was calculated.Results
Of 298 patients, 31 (10.8%) had previous VFs at baseline. A total of 30 new VFs occurred in 26 patients over 4 years. The incidence of morphometric VFs was 4.7% at 2 years and 13.6% at 4 years. Multivariate logistic regression analysis showed that previous VFs at baseline and increased CRP levels at 2 years were predictors of new VFs (odds ratio (OR) =12.8, 95% confidence interval (CI) = 3.6-45.3 and OR = 5.4, 95% CI = 1.4–15.9). The age-specific specific standardized prevalence ratio of morphometric VFs in AS was 3.3 (95% CI 2.1–4.5).Conclusions
The incidence of morphometric VFs increased in AS. Previous VFs and increased CRP levels predicted future VFs. Further studies are needed to identify the effects of treatment interventions on the prevention of new VFs. 相似文献15.
Kai-Michael Beeh Craig LaForce Martina Gahlemann Arne Wenz Robert Toorawa Matja? Fle?ar 《Respiratory research》2015,16(1)
Background
A Phase II, multicentre, randomised, double-blind, placebo-controlled, crossover trial comparing the 24-h forced expiratory volume in 1 s (FEV1) time profile after 3 weeks’ treatment with once-daily (QD) or twice-daily (BID) olodaterol (at the same total daily dose) versus placebo delivered via Respimat® in patients with moderate to severe asthma.Methods
Patients were randomised to different sequences of olodaterol with 2-week washout, either as a total daily dose of 5 μg (5 μg QD [AM] or 2.5 μg BID) or placebo, or 10 μg (10 μg QD [AM] or 5 μg BID) or placebo. Primary end point was FEV1 area under the curve from 0 to 24 h (AUC0–24) response (defined as change from study baseline FEV1) after 3 weeks. Key secondary end points were FEV1 AUC0–12 and AUC12–24 responses.Results
Two hundred and six patients received treatment. All olodaterol treatments demonstrated statistically significant improvements in FEV1 AUC0–24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment difference versus placebo was 0.191 L for olodaterol 2.5 μg BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for 5 μg QD (95 % CI 0.111, 0.189), 0.228 L for 5 μg BID (95 % CI 0.190, 0.266) and 0.209 L for 10 μg QD (95 % CI 0.170, 0.247). These results were supported by the key secondary end points. Olodaterol 5 μg QD provided numerically lower mean values for 24-h bronchodilation than olodaterol 2.5 μg BID (p = 0.0465), with no statistically significant difference between treatment with olodaterol 10 μg QD and 5 μg BID. No relevant differences in morning and evening peak expiratory flow or Asthma Control Questionnaire scores at 3 weeks were observed between different doses and regimens. Adverse events were generally mild to moderate and comparable between groups.Conclusions
All doses and dose frequencies provided adequate 24-h bronchodilation superior to placebo. Based on the results of this study, it would be reasonable to include both posologies of 5 μg olodaterol daily (5 μg QD or 2.5 μg BID, both delivered in two puffs per dose from the Respimat® inhaler) in subsequent studies. Further studies are necessary to confirm the optimum dosing regimen in asthma. No safety concerns were identified.Trial registration
ClinicalTrials.gov NCT01311661Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0243-1) contains supplementary material, which is available to authorized users. 相似文献16.
Rojane de Oliveira Paiva Lucimar Ferreira Kneipp Camilla Moretto dos Reis Aurea Echevarria 《BMC microbiology》2015,15(1)
Background
Fungi contaminate the food of humans and animals, are a risk to health, and can cause financial losses. In this work, the antifungal activities of 16 mesoionic compounds (MI 1–16) were evaluated against mycotoxigenic fungi, including Aspergillus spp., Fusarium verticillioides and Penicillium citrinum. Furthermore, the decreased ergosterol in the total lipid content of Fusarium verticillioides was investigated.Results
F. verticillioides was the most sensitive fungus to the mesoionic compounds. Among the evaluated compounds, MI-11 and MI-16 presented higher antifungal effects against F. verticillioides, with MIC values of 7.8 μg/ml, and MI-2 and MI-3 followed, with MICs of 15.6 μg/ml. The most active compounds were those with heterocyclic ring phenyl groups substituted by electron donor moieties (MI-11 and MI-16). Among some compounds with higher activity (MI-2, MI-11 and MI-16), decreased ergosterol content in the total lipid fraction of F. verticillioides was demonstrated. MI-2 reduced the ergosterol content approximately 40% and 80% at concentrations of 7.8 μg/ml and 15.6 μg/ml, respectively, and MI-11 and MI-16 decreased the content by 30% and 50%, respectively, when at a concentration of 7.8 μg/ml.Conclusion
These findings indicate that mesoionic compounds have significant antifungal activity against F. verticillioides. 相似文献17.
18.
Syed Muhammad Mukarram Shah Abdul Sadiq Syed Muhammad Hassan Shah Shahzeb Khan 《Biological research》2014,47(1)
Background
The current era is facing challenges in the management of neoplasia and weeds control. The currently available anti-cancer and herbicidal drugs are associated with some serious side effects. Therefore numerous researchers are trying to discover and develop plant based alternative particularly for the rational management of cancer and weed control. Teucrium stocksianum possess antioxidant and analgesic activities. The current study was designed to evaluate crude saponins (CS), methanolic extract and sub-fractions of T. stocksianum for cytotoxic and phytotoxic potentials. CS, methanolic extract and sub-fractions were extracted from powdered plant material using different solvents. Cytotoxic potential of the extracts at a dose of 10, 100 and 1000 μg/ml were evaluated against Brine shrimp’s nauplii. Phytotoxic assay also performed at the same concentration against Lemna minor. Etoposide and Paraquat were used as positive controls in cytotoxic and phytotoxic assays respectively.Results
The percent yield of crude saponins was (5%). CS demonstrated tremendous brine shrimp lethality showing < 10 μg/ml LC50. The n-hexane (HF) and chloroform fractions (CF) demonstrated excellent cytotoxicity with 80 and 55 μg/ml LC50 respectively. Whereas the methanolic extract (TSME), ethyl acetate (EAF) and aqueous fractions (AF) revealed moderate cytotoxicity showing 620, 860 and 1000 μg/ml LC50 values respectively. In phytotoxic assay profound inhibition was displayed by HF (96.67%) and TSME (95.56%, 30 μg/ml LC50) against the growth of Lemna minor at 1000 μg/ml respectively. Both CF and EAF demonstrated profound phytoxicity (93.33%) respectively at highest concentration (1000 μg/ml), while AF and CS demonstrated weak phytotoxicity with 1350 and 710 μg/ml LC50 values respectively.Conclusion
Cytotoxicity and phytotoxicity assays indicated that the crude saponins, n-hexane and chloroform fractions of T. stocksianum could play a vital role in the treatment of neoplasia and as potential natural herbicides. Therefore these sub-fractions are recommended for further investigation with the aim to isolate novel anti-cancer and herbicidal compounds. 相似文献19.
Background
Susceptibility to and severity of ankylosing spondylitis (AS) are largely genetically determined. PPARGC1B, RUNX3 and TBKBP1 have recently been found to be associated with AS in patients of western European descent. Our purpose is to examine the influence of PPARGC1B, RUNX3 and TBKBP1 polymorphisms on the susceptibility to and the severity of ankylosing spondylitis in Chinese ethnic majority Han population.Methods
Blood samples are drawn from 396 AS patients and 404 unrelated healthy controls. All the patients and the controls are Han Chinese and the patients are HLA-B27 positive. The AS patients are classified based on the severity of the disease. Twelve tag single nucleotide polymorphisms (tagSNPs) in PPARGC1B, RUNX3 and TBKBP1 are selected and genotyped. Frequencies of different genotypes and alleles are analyzed among the different severity AS patients and the controls.Results
After Bonferroni correction, the rs7379457 SNP in PPARGC1B shows significant difference when comparing all AS patients to controls (p = 0.005). This SNP also shows significant difference when comparing normal AS patients to controls (p = 0.002). The rs1395621 SNP in RUNX3 shows significant difference when comparing severe AS patients to controls (p = 0.007). The rs9438876 SNP in RUNX3 shows significant difference when comparing normal AS patients to controls (p = 0.007). The rs8070463 SNP in TBKBP1 shows significant difference in genotype distribution when comparing severe AS patients to controls (p = 0.003).Conclusions
The rs7379457 SNP in PPARGC1B is related to susceptibility to AS in Chinese Han population. The rs7379457 SNP in PPARGC1B, the rs1395621 and rs9438876 SNPs in RUNX3, and the rs8070463 SNP in TBKBP1 are related to the severity of AS in Chinese Han population. 相似文献20.
Shan Shan Jie Dang Jiangxia Li Ze Yang Hailing Zhao Qian Xin Xiaochun Ma Yongchao Liu Xianli Bian Yaoqin Gong Qiji Liu 《Arthritis research & therapy》2014,16(2):R87