Ankylosing Spondylitis Treatment Report

www.AnkylosingSpondylitisTreatmentReport.com

Research

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings

https://journals.lww.com/jclinrheum/Abstract/9000/Pain_and_Fatigue_in_Patients_With_Ankylosing.98555.aspx

https://www.ncbi.nlm.nih.gov/pubmed/32826654?dopt=Abstract

TITLE:
Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

DESCRIPTION:
Related Articles

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

J Clin Rheumatol. 2020 Aug 20;:

Authors: Strand V, Deodhar A, Alten R, Sullivan E, Blackburn S, Tian H, Gandhi KK, Jugl SM, Conaghan PG

Abstract

BACKGROUND/OBJECTIVE: Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity.

METHODS: Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment.

RESULTS: Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. CONCLUSIONS: Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways. PMID: 32826654 [PubMed - as supplied by publisher] PMID: PubMed:32826654 DATE FOUND: 08/23/20 06:29AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32826654?dopt=Abstract

Is fibromyalgia frequency increasing in axial spondyloarthritis? Association with fibromyalgia and biological therapies

https://link.springer.com/article/10.1007/s00296-020-04670-w

https://www.ncbi.nlm.nih.gov/pubmed/32767083?dopt=Abstract

TITLE:
Is fibromyalgia frequency increasing in axial spondyloarthritis? Association with fibromyalgia and biological therapies.

DESCRIPTION:
Related Articles

Is fibromyalgia frequency increasing in axial spondyloarthritis? Association with fibromyalgia and biological therapies.

Rheumatol Int. 2020 Aug 07;:

Authors: Sayın S, Yurdakul FG, Sivas F, Bodur H

Abstract

Fibromyalgia (FM) is known a common painful syndrome and its frequency is increased in inflammatory rheumatic diseases. We aimed to assess FM frequency in axial spondyloarthritis (AxSpA) patients and age- and sex-matched healthy controls with the 2011 ACR FM criteria. We evaluated the association between receiving biologic disease-modifying antirheumatoid drugs (bDMARD) and presence of FM. 127 patients with Ax-SpA and 73 age- and sex-matched controls were included. Individuals were assessed according to modified 2011 ACR diagnostic criteria for FM. The pain was evaluated by visual analog scale (VAS). Disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activation Score (ASDAS). Spinal limitation, quality of life, and functionality were assessed. Drug therapies were noted. AxSpA and control group had similar FM rates. 43 (33.9%) patients in AxSpA group and 22 (30.1%) patients in control group had FM diagnosis (p = 0.589). Age, gender, BMI, and CRP values were similar in the AxSpA patients with and without FM, while global VAS and ASDAS scores were higher in patients with FM. Biologic DMARD use was higher in the AxSpA patients with FM; however, the difference was not statistically significant. In conclusion, FM frequency does not increase in AxSpA patients as compared to healthy controls. FM awareness is one of the key points to determine the appropriate treatment due to the influence on disease activity.

PMID: 32767083 [PubMed – as supplied by publisher]

PMID:
PubMed:32767083

DATE FOUND:
08/09/20 06:45AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32767083?dopt=Abstract

A prospective study of novel disease activity indices for ankylosing spondylitis

https://link.springer.com/article/10.1007%2Fs00296-020-04662-w

https://www.ncbi.nlm.nih.gov/pubmed/32757024?dopt=Abstract

TITLE:
A prospective study of novel disease activity indices for ankylosing spondylitis.

DESCRIPTION:
Related Articles

A prospective study of novel disease activity indices for ankylosing spondylitis.

Rheumatol Int. 2020 Aug 05;:

Authors: Sundaram TG, Muhammed H, Aggarwal A, Gupta L

Abstract

There is an ongoing quest for robust disease activity measures in Ankylosing spondylitis (AS). Thus, we prospectively validated two new disease activity indices, Simplified AS Disease Activity Score (SASDAS) and modified Juvenile Spondyloarthritis Disease Activity Score (JSpADA). Patients with AS were assessed for BASDAI, ASDAS and other outcome measures at baseline and 3 months. Comparisons were drawn between those with juvenile onset, early disease and peripheral involvement, with the rest. Fisher’s r to Z transformation was used to compare correlations. Receiver-operating characteristic (ROC) curves were used to calculate cutoffs for inactive, low, high and very high disease activity. Of the 107 patients (mean age-29 years) of 6-years long disease, 38.3% had a juvenile onset. SASDAS and modified JSpADA exhibited excellent correlation with BASDAI and ASDAS (all p < 0.001) and were higher in active vs. inactive disease. Treatment responders had a greater fall in SASDAS and modified JSpADA as compared to non-responders. The novel scores were higher in those with peripheral disease. Only SASDAS could discriminate early from late disease. Based on the previously proposed cutoffs, optimal scores for inactive, moderate, high and very high disease activity were deduced. SASDAS-CRP showed better internal consistency than SASDAS-ESR and correlated better with ASDAS-CRP in late disease (Z = 3.04; p = 002) and those with adult onset disease (Z = 2.18; p = 0.03). SASDAS and Modified JSpADA perform as well as standard complex scores and have potential for simpler daily use. From our analyses, SASDAS with CRP performs better than SASDAS-ESR, pending further validation. PMID: 32757024 [PubMed - as supplied by publisher] PMID: PubMed:32757024 DATE FOUND: 08/07/20 06:15AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32757024?dopt=Abstract

Anemia in patients with ankylosing spondylitis, association with the activity of the inflammatory process and the severity of the disease

https://www.ncbi.nlm.nih.gov/pubmed/32731703?dopt=Abstract

TITLE:
Anemia in patients with ankylosing spondylitis, association with the activity of the inflammatory process and the severity of the disease.

DESCRIPTION:
Related Articles

Anemia in patients with ankylosing spondylitis, association with the activity of the inflammatory process and the severity of the disease.

Wiad Lek. 2020;73(4):715-721

Authors: Zviahina OV, Shevchuk SV, Kuvikova IP, Segeda IS

Abstract

OBJECTIVE: The aim: To estimate the prevalence of anemia in patients with ankylosing spondylitis, major pathogenetic variants and their relationship with the activity of the inflammatoryprocess and the severity of the disease.

PATIENTS AND METHODS: Materials and methods: 118 patients with ankylosing spondylitis participated in the study, which performed hematologic, biochemical, immunological studies with general haemopoiesis and ferrokinetics parameters, plasma levels of CRP and IL-6.

RESULTS: Results: It was found that in Ukrainian population of patients with ankylosing spondylitis, 28.8% of patients has anemic syndrome. The anemia spectrum is represented by ACD (44.1%), ACD with iron deficiency (29.4%) and IDA (23.5%). It is shown that the severity of anemic syndrome increases with the increase of the stage of activity of the inflammatory process. The presence and severity of anemia are closely related to the severe course of the disease, evaluated by the BASDAI and ASDAS index, and laboratory markers of inflammation CRP and IL-6 of serum.

CONCLUSION: Conclusions: The obtained data is promising for the search of effective means of correction of anemic syndrome in patients with ankylosing spondylitis.

PMID: 32731703 [PubMed – in process]

PMID:
PubMed:32731703

DATE FOUND:
08/01/20 06:39AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32731703?dopt=Abstract

The effectiveness of Du moxibustion for ankylosing spondylitis: A protocol for systematic review and meta-analysis of randomized clinical trials

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402767/

https://www.ncbi.nlm.nih.gov/pubmed/32756165?dopt=Abstract

TITLE:
The effectiveness of Du moxibustion for ankylosing spondylitis: A protocol for systematic review and meta-analysis of randomized clinical trials.

DESCRIPTION:
Related Articles

The effectiveness of Du moxibustion for ankylosing spondylitis: A protocol for systematic review and meta-analysis of randomized clinical trials.

Medicine (Baltimore). 2020 Jul 31;99(31):e21450

Authors: Huang S, Li H, Xiong J, Hua F, Xiang J, Jiang Y

Abstract

BACKGROUND: Ankylosing spondylitis (AS) is a common progressive autoimmune inflammatory disease. Du moxibustion can effectively treat AS with few adverse reactions. The aim of this protocol is to systematically investigate the effectiveness and safety for management of AS with Du moxibustion.

METHODS: Seven relevant databases, namely, PubMed, Cochrane Library, Embase, Chinese Biomedical Literatures Database (CBM), China National Knowledge Infrastructure (CNKI), WangFang Database (WF), Chinese Scientific Journal Database (VIP) will be searched from their inception until May 1st, 2020. All clinical randomized controlled trials containing eligible interventions(s) and outcome(s) will be included, regardless of blinding or publication types. Two reviewers will independently retrieval databases, extract data, and then assess the quality of studies. Data synthesis will be conducted by RevMan 5.3 software. We regard the effective rate, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analogue Scale (VAS) as the primary outcomes, and the secondary outcomes contain C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), finger-to-floor distance (FFD), occiput to wall distance (OWD), and side effects. The result about the curative effect and safety of Du moxibustion for AS will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data.

RESULTS: The finding will be presented in a journal or related conferences.

CONCLUSIONS: This study expects to provide high-quality, evidence-based recommendations on further treatment for clinical guidance.

PROSPERO REGISTRATION NUMBER: CRD42020158727.

PMID: 32756165 [PubMed – in process]

PMID:
PubMed:32756165

DATE FOUND:
08/07/20 06:37AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32756165?dopt=Abstract

GM-CSF Primes Proinflammatory Monocyte Responses in Ankylosing Spondylitis

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01520/full

https://www.ncbi.nlm.nih.gov/pubmed/32765525?dopt=Abstract

TITLE:
GM-CSF Primes Proinflammatory Monocyte Responses in Ankylosing Spondylitis.

DESCRIPTION:
Related Articles

GM-CSF Primes Proinflammatory Monocyte Responses in Ankylosing Spondylitis.

Front Immunol. 2020;11:1520

Authors: Shi H, Chen L, Ridley A, Zaarour N, Brough I, Caucci C, Smith JE, Bowness P

Abstract

Objectives: GM-CSF is a pro-inflammatory cytokine with multiple actions predominantly on myeloid cells. Enhanced GM-CSF expression by lymphocytes from patients with Ankylosing Spondylitis (AS) has recently been described, however, its potential pathogenic role(s) in AS are unknown. Methods: The effects of GM-CSF on TNF, IL-23, and CCL17 production by blood, PBMCs and isolated CD14+ monocytes from AS patients and healthy controls (HCs) were studied using ELISA. Serum CCL17 and GM-CSF and T cell GM-CSF production were studied in AS patients including pre-and on TNFi therapy. Results: GM-CSF markedly increased TNF production by LPS-stimulated whole blood, peripheral blood mononuclear cells (PBMC) and purified monocytes from AS patients, with 2 h GM-CSF exposure sufficient for monocyte “priming.” Blocking of GM-CSF significantly reduced the production of TNF by whole blood from AS patients but not HCs. GM-CSF priming increased IL-23 production from LPS-stimulated AS and HC whole blood 5-fold, with baseline and stimulated IL-23 levels being significantly higher in AS whole blood. GM-CSF also stimulated CCL17 production from AS and HC blood and CCL17 levels were elevated in AS plasma. GM-CSF could be detected in plasma from 14/46 (30%) AS patients compared to 3/18 (17%) HC. Conclusion: We provide evidence that GM-CSF primes TNF and IL-23 responses in myeloid cells from AS patients and HC. We also show CCL17 levels, downstream of GM-CSF, were elevated in plasma samples of AS patients. Taken together these observations are supportive of GM-CSF neutralization as a potential novel therapeutic approach for the treatment of AS.

PMID: 32765525 [PubMed – as supplied by publisher]

PMID:
PubMed:32765525

DATE FOUND:
08/09/20 07:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32765525?dopt=Abstract

The changing profile of ankylosing spondylitis in the biologic era

https://link.springer.com/article/10.1007%2Fs10067-020-05260-8

https://www.ncbi.nlm.nih.gov/pubmed/32648102?dopt=Abstract

TITLE:
The changing profile of ankylosing spondylitis in the biologic era.

DESCRIPTION:
Related Articles

The changing profile of ankylosing spondylitis in the biologic era.

Clin Rheumatol. 2020 Jul 09;:

Authors: Reveille JD, Lee M, Gensler LS, Ward MM, Hwang MC, Learch TJ, Tahanan A, Diekman L, Rahbar MH, Ishimori ML, Weisman MH

Abstract

OBJECTIVE: To compare disease characteristics, comorbidities, and medication utilization of 1141 patients with ankylosing spondylitis (AS) with short (< 20 years) and long (≥ 20 years) disease duration enrolled in the Prospective Study of Outcomes in AS (PSOAS) study over three different periods of time and followed longitudinally. METHODS: Study visits were carried out every 6 months examining disease activity (Bath AS Disease Activity Index (BASDAI), C-reactive protein, erythrocyte sedimentation rate), functional impairment, depression, and medication utilization as well as radiographic severity. Groups were compared with regression models using generalized estimating equation, linear, and Poisson regressions after adjusting for sites and for patients withdrawing from the study at less than 2 years follow-up. RESULTS: Overall, AS patients with long disease duration were more likely to be married, white, receiving disability, and to be with higher functional impairment and radiographic severity, more uveitis, diabetes, hypertension, cardiovascular disease, and osteoporosis, and with less nonsteroidal anti-inflammatory drug (NSAID) and more opioid use than those with short disease duration. Current smoking decreased between 2002 and 2019 regardless of disease duration. Lower baseline NSAID and methotrexate/sulfasalazine use and higher TNF inhibitor usage were seen only in those with shorter disease duration, though NSAID use and functional impairment decreased over time in both groups. Disease activity, depression scores, and NSAID use decreased and anti-TNF use increased in those followed > 8 years.

CONCLUSIONS: Patients with AS enrolling in this multicenter longitudinal cohort have different disease profiles and medication utilization over time, perhaps reflecting innovations in treatment and increasing disease awareness. Key Points • The use of NSAIDs, nonbiologic DMARDs, and prednisone has decreased over the past 16 years in patients with AS. • The use of anti-TNF agents has dramatically increased. • In treated patients, disease activity, depression scores, and functional impairment have decreased over time.

PMID: 32648102 [PubMed – as supplied by publisher]

PMID:
PubMed:32648102

DATE FOUND:
07/11/20 06:43AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32648102?dopt=Abstract

MicroRNA‑204‑5p inhibits the osteogenic differentiation of ankylosing spondylitis fibroblasts by regulating the Notch2 signaling pathway

https://www.spandidos-publications.com/10.3892/mmr.2020.11303

https://www.ncbi.nlm.nih.gov/pubmed/32705191?dopt=Abstract

TITLE:
MicroRNA‑204‑5p inhibits the osteogenic differentiation of ankylosing spondylitis fibroblasts by regulating the Notch2 signaling pathway.

DESCRIPTION:
Related Articles

MicroRNA‑204‑5p inhibits the osteogenic differentiation of ankylosing spondylitis fibroblasts by regulating the Notch2 signaling pathway.

Mol Med Rep. 2020 Sep;22(3):2537-2544

Authors: Zhao J, Zhang Y, Liu B

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory systemic disease and is difficult to detect in the early stages. The present study aimed to investigate the role of microRNA (miR)‑204‑5p in osteogenic differentiation of AS fibroblasts. Bone morphogenetic protein 2 (BMP‑2) was used to induce osteogenic differentiation. Cells were divided into the following groups: AS group, AS + BMP‑2 group, AS + BMP‑2 + miR‑negative control group, AS + BMP‑2 + miR‑204‑5p mimics group and AS + BMP‑2 + miR‑204‑5p mimics + pcDNA‑Notch2 group. The expression levels of miR‑204‑5p, Notch2, runt‑related transcription factor 2 (RUNX2) and osteocalcin were detected via reverse transcription‑quantitative PCR analysis. The binding site between Notch2 and miR‑204‑5p was predicted using TargetScan software and verified via the dual‑luciferase reporter assay. Alkaline phosphatase (ALP) activity was assessed via the ALP assay, while the mineralized nodules area was determined via the Alizarin Red S staining assay. The results demonstrated that Notch2 is a target gene of miR‑204‑5p. Furthermore, treatment with BMP‑2 significantly decreased miR‑204‑5p expression, and significantly increased ALP activity, the mineralized nodules area and the expression levels of Notch2, RUNX2 and osteocalcin in ligament fibroblasts (all P<0.05). Conversely, transfection with miR‑204‑5p mimics significantly increased miR‑204‑5p expression, and significantly decreased ALP activity, the mineralized nodules area and the expression levels of Notch2, RUNX2 and osteocalcin in ligament fibroblasts (all P<0.05). Notably, transfection with pcDNA‑Notch2 significantly reversed the inhibitory effects induced by miR‑204‑5p mimics on the osteogenic differentiation of ligament fibroblasts (all P<0.05). Furthermore, miR‑204‑5p inhibited the osteogenic differentiation of ligament fibroblasts in patients with AS by targeting Notch2. Thus, miR‑204‑5p may negatively regulate Notch2 expression and may be a potential therapeutic target for AS. Collectively, the results of the present study provide a theoretical basis for the effective treatment of patients with AS. PMID: 32705191 [PubMed - in process] PMID: PubMed:32705191 DATE FOUND: 07/27/20 02:02PM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32705191?dopt=Abstract

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02226-8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304211/

https://www.ncbi.nlm.nih.gov/pubmed/32560733?dopt=Abstract

TITLE:
TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis.

DESCRIPTION:
Related Articles

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis.

Arthritis Res Ther. 2020 Jun 19;22(1):149

Authors: Yang M, Lv Q, Wei Q, Jiang Y, Qi J, Xiao M, Fang L, Xie Y, Cao S, Lin Z, Zhang Y, Tu L, Zhao M, Pan Y, Jin O, Gu J

Abstract

BACKGROUND: Studies into ankylosing spondylitis (AS) and its relationship with immune imbalance are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune imbalance is unclear.

METHODS: A total of 40 immune cells were tested with flow cytometry, and the results of 105 healthy control (HC) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed.

RESULTS: Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (P < 0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (P < 0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (P < 0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (P < 0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (P < 0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (P < 0.001, 0.0001, and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (P < 0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (P < 0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (P < 0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (P < 0.01 and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in C-reactive protein (CRP) (r = 0.489, P = 0.018). CONCLUSIONS: We found that active-stage AS patients have an immunity imbalance of frequency involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells in frequency. But CD8+ T cells have not been rescued. PMID: 32560733 [PubMed - as supplied by publisher] PMID: PubMed:32560733 DATE FOUND: 06/21/20 06:35AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32560733?dopt=Abstract

The Efficacy and Safety of Simple-Needling Therapy for Treating Ankylosing Spondylitis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306850/

https://www.hindawi.com/journals/ecam/2020/4276380/

https://www.ncbi.nlm.nih.gov/pubmed/32617106?dopt=Abstract

TITLE:
The Efficacy and Safety of Simple-Needling Therapy for Treating Ankylosing Spondylitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

DESCRIPTION:
Related Articles

The Efficacy and Safety of Simple-Needling Therapy for Treating Ankylosing Spondylitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med. 2020;2020:4276380

Authors: Xuan Y, Huang H, Huang Y, Liu D, Hu X, Geng L

Abstract

Background: Clinical investigators have found that the use of needling in the treatment of ankylosing spondylitis (AS) has a good clinical application prospect in recent years. However, these studies were insufficient to provide evidence for the efficacy and safety of simple-needling for AS. So, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of simple-needling for treating AS.

Methods: We searched the PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wangfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), and any other gray literature sources for randomized controlled trials (RCTs) that used simple-needling to treat AS before June 2019 with the language restriction of Chinese and English. Researchers evaluated the retrieved literature studies and extracted valid data according to relevant requirements and used RevMan5.3 software for meta-analysis.

Results: A total of 10 studies were included, all of which were Chinese literature studies, involving 729 patients. Compared with the control groups, simple-needling groups had a better effect on the clinical effective rate (RR = 1.20, 95% CI (1.11, 1.29), P < 0.00001), TCM syndrome score (MD = -5.26, 95% CI (-5.99, -4.53), P < 0.00001), symptom score (MD = -8.08, 95% CI (-10.18, -5.97), P < 0.00001), and Schober test outcome (MD = 0.39, 95% CI (0.15, 0.64), P=0.002). Sensibility analysis was based on the leave-one-out cross-validation procedure, and the results showed no significant changes. Most studies did not describe adverse reactions. The funnel plot suggested publication bias on clinical effectiveness. Conclusions: This systematic review and meta-analysis demonstrated that simple-needling was effective as an intervention for AS. However, due to the low quality of the methodology of included studies, the designs of clinical trials were not rigorously standardized. Therefore, it is necessary to carry out multiquality RCTs for verification. PMID: 32617106 [PubMed] PMID: PubMed:32617106 DATE FOUND: 07/05/20 03:28PM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32617106?dopt=Abstract

IL6 May Represent a Useful Biomarker for Diagnosing Ankylosing Spondylitis

https://www.hindawi.com/journals/bmri/2020/5304578/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298317/

https://www.ncbi.nlm.nih.gov/pubmed/32596323?dopt=Abstract

TITLE:
RNA Sequencing for Gene Expression Profiles in Peripheral Blood Mononuclear Cells with Ankylosing Spondylitis RNA.

DESCRIPTION:
Related Articles

RNA Sequencing for Gene Expression Profiles in Peripheral Blood Mononuclear Cells with Ankylosing Spondylitis RNA.

Biomed Res Int. 2020;2020:5304578

Authors: Huang D, Liu J, Cao Y, Wan L, Jiang H, Sun Y, Wen J

Abstract

Several previous studies have attempted to investigate the regulatory mechanisms underlying gene expression in ankylosing spondylitis (AS). However, the specific molecular pathways underlying this condition remain unclear. Previous research used next-generation RNA sequencing to identify a series of differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) when compared between patients with AS and healthy controls, thus implying that these DEGs may be related to AS. Furthermore, by screening these DEGS, it may be possible to facilitate clinical diagnosis and optimize treatment strategies. In order to test this hypothesis, we recruited 15 patients with AS and 15 healthy controls. We randomly selected five subjects from each group of patients for RNA sequencing analysis. Sequence reads were generated by an Illumina HiSeq2500 platform and mapped on to the human reference genome using HISAT2. We successfully identified 973 significant DEGs (p < 0.05) in PBMCs. When compared with controls, 644 of these genes were upregulated (with a fold change (FC) > 2) in AS patients and 329 were downregulated (FC < 0.5). Our analysis identified numerous genes related to immune response. Gene Ontology (GO) analysis indicated that these DEGs were significantly related to the positive regulation of epidermal growth factor-activated receptor activity, the positive regulation of the ERBB (erb-b2 receptor tyrosine kinase) signaling pathway, the differentiation of trophoblast giant cells, oxygen transport, immune-related pathways, and inflammation-related pathways. The DEGs were also closely related to the TNF and NF-κB signaling pathways. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curve analysis indicated that IL6 may represent a useful biomarker for diagnosing AS. The development of new biomarkers may help us to elucidate the specific mechanisms involved in the development and progression of AS. PMID: 32596323 [PubMed - in process] PMID: PubMed:32596323 DATE FOUND: 07/01/20 07:32AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32596323?dopt=Abstract

Molecular mechanisms and clinical studies of iguratimod for the treatment of ankylosing spondylitis

https://link.springer.com/article/10.1007%2Fs10067-020-05207-z

https://www.ncbi.nlm.nih.gov/pubmed/32506313?dopt=Abstract

TITLE:
Molecular mechanisms and clinical studies of iguratimod for the treatment of ankylosing spondylitis.

DESCRIPTION:
Related Articles

Molecular mechanisms and clinical studies of iguratimod for the treatment of ankylosing spondylitis.

Clin Rheumatol. 2020 Jun 06;:

Authors: Liu S, Cui Y, Zhang X

Abstract

Iguratimod (IGU) is a novel small molecule anti-rheumatic drug with the effect of non-steroidal anti-inflammatory drug and disease-modifying anti-rheumatic drug. IGU has various mechanisms of action, including inhibition of prostaglandin E2, tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) production, inhibition of macrophage migration inhibitory factor (MIF)-induced proinflammatory effects, inhibition of osteoclastogenesis, and promotion of osteoblastic differentiation. Ankylosing spondylitis (AS) is the major subtype of spondyloarthritis that affects the axial skeleton, causing inflammatory back pain, which can lead to impairments in structure and function and a decrease in quality of life. Theories on pathogenesis of AS include misfolding of human leukocyte antigen-B27 during its assembly leading to endoplasmic reticulum stress and unfolded protein response (UPR). Activation of UPR genes results in release of TNF-α and IL-17, which have been shown to be important in the development of AS. In addition, current evidence suggests the importance of cyclooxygenase-2/prostaglandin E2 pathway and MIF in the pathogenesis of AS. Current drugs for the treatment of AS are limited and exploration of effective drugs is needed. IGU may be effective for the treatment of AS given that its mechanisms of action are closely related to the pathogenesis of AS. In fact, several small-scale clinical trials have shown the efficacy of IGU for the treatment of AS. This article reviews the molecular mechanisms of IGU that are related to the pathogenesis of AS and clinical trials of IGU for the treatment of AS, providing a reference for future clinical application of IGU for AS.

PMID: 32506313 [PubMed – as supplied by publisher]

PMID:
PubMed:32506313

DATE FOUND:
06/09/20 06:49AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32506313?dopt=Abstract

Down-regulated miR-495 can target programmed cell death 10 in ankylosing spondylitis: a potential molecular marker for the diagnosis and treatment of AS

https://molmed.biomedcentral.com/articles/10.1186/s10020-020-00157-3

https://www.ncbi.nlm.nih.gov/pubmed/32450789?dopt=Abstract

TITLE:
Down-regulated miR-495 can target programmed cell death 10 in ankylosing spondylitis.

DESCRIPTION:
Related Articles

Down-regulated miR-495 can target programmed cell death 10 in ankylosing spondylitis.

Mol Med. 2020 May 25;26(1):50

Authors: Ni WJ, Leng XM

Abstract

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression. Recent studies indicated that aberrantly expressed miRNAs are involved in the pathogenesis of ankylosing spondylitis (AS). Indeed, hsa-miR-495-3p (miR-495) has been reported as an anti-oncogene in different cancers. However, the role of miR-495 in AS is still unknown.

METHODS: In this study, quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of miR-495 in the peripheral blood mononuclear cells (PBMCs), whole blood, and serum of patients with AS. Bisulfite-specific PCR sequencing and methylated DNA immunoprecipitation were used to detect the methylation in the promoter region of miR-495. To determine the influence of miR-495 expression on the target gene, programmed cell death 10 (PDCD10), dual luciferase reporter assays together with an adenoviral vector containing the miR-495 locus were used. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of miR-495 as a diagnostic biomarker of AS. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and western blotting were used to explore the potential role of miR-495 in AS pathogenesis and the mechanism by which it facilitates AS pathogenesis.

RESULTS: miR-495 is down-regulated and the promoter region of miR-495 is highly methylated in AS. The expression of miR-495 is negatively associated with PDCD10 expression in both patients with AS and healthy controls. Further experiments showed that PDCD10 can be targeted by miR-495. The ROC curves of miR-495 suggested that it is a very specific and sensitive biomarker for AS diagnosis. Bioinformatics analysis and signal pathway studies indicated that miR-495 can down-regulate β-catenin and transforming growth factor-β1.

CONCLUSIONS: Our studies indicated that down-regulation of miR-495 can be used as a potential molecular marker for the diagnosis and treatment of AS, thus providing new insights into the role of miRNAs in AS pathology.

PMID: 32450789 [PubMed – in process]

PMID:
PubMed:32450789

DATE FOUND:
05/27/20 07:21AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32450789?dopt=Abstract

Dihydrotestosterone (DHT) inhibition might increase the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients

https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02217-9

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245802/

https://www.ncbi.nlm.nih.gov/pubmed/32448352?dopt=Abstract

Dihydrotestosterone (DHT) inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients

Effects of dihydrotestosterone (DHT) on osteoblast activity in mice and osteoprogenitor cells in patients with ankylosing spondylitis

TITLE:
Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.

DESCRIPTION:
Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.

Arthritis Res Ther. 2020 May 24;22(1):121

Authors: Jo S, Lee EJ, Nam B, Kang J, Lee S, Youn J, Park YS, Kim YG, Kim TH

Abstract

BACKGROUND: Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood.

METHODS: In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients.

RESULTS: In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro.

CONCLUSIONS: Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

PMID: 32448352 [PubMed – in process]

PMID:
PubMed:32448352

DATE FOUND:
05/26/20 06:21AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32448352?dopt=Abstract

Clinical efficacy of golimumab in the treatment of ankylosing spondylitis

https://link.springer.com/article/10.1007%2Fs00586-020-06466-9

https://www.ncbi.nlm.nih.gov/pubmed/32447529?dopt=Abstract

TITLE:
Patients with ankylosing spondylitis treatment by golimumab: a systematic review and meta-analysis.

DESCRIPTION:
Patients with ankylosing spondylitis treatment by golimumab: a systematic review and meta-analysis.

Eur Spine J. 2020 May 23;:

Authors: Sayed Abdulla J, Shi J, Roy BS, Zhanwen Z, Liu C

Abstract

PURPOSE: The goal of this study was to review relevant randomized controlled trials in order to determine the clinical efficacy of golimumab in the treatment of ankylosing spondylitis (AS).

METHODS: Using appropriate keywords, we identified relevant studies using PubMed, Cochrane and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through November 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference and 95% confidence interval to assess and synthesize outcomes.

RESULTS: We included nine studies with 6363 patients. Compared with placebo, golimumab would significant decreased the value of BASFI, BASMI, BASDAI, total back pain, JSEQ; increased the value of SF-36 PCS and SF-36 MCS; increased the incidence of BASDAI50, ASAS20, ASAS40 and ASAS partial remission. Compared with golimumab 50 mg, golimumab 100 mg would significantly decreased the value of BASFI and total back pain; increased the value of SF-36 PCS and SF-36 MCS; but also increased the incidence of SAE.

CONCLUSIONS: Golimumab had a definite effect in the treatment of AS. The higher dose would obtain better efficacy but lead to the incidence of SAE.

PMID: 32447529 [PubMed – as supplied by publisher]

PMID:
PubMed:32447529

DATE FOUND:
05/25/20 06:26AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32447529?dopt=Abstract

Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

https://onlinelibrary.wiley.com/doi/abs/10.1111/1756-185X.13829

https://www.ncbi.nlm.nih.gov/pubmed/32419337?dopt=Abstract

TITLE:
Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

DESCRIPTION:
Related Articles

Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

Int J Rheum Dis. 2020 May 17;:

Authors: Ajrawat P, Touma Z, Sari I, Taheri C, Diaz Martinez JP, Haroon N

Abstract

To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1 year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4 years [range 25.3-50 years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4 years of follow-up and >4 years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8 years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P = .01; I2  = 0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P = .06; I2  = 0%). This systematic review and meta-analysis indicated that >4 years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4 years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.

PMID: 32419337 [PubMed – as supplied by publisher]

PMID:
PubMed:32419337

DATE FOUND:
05/19/20 06:22AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32419337?dopt=Abstract

Efficacy and Safety of Sinomenine Preparation for Ankylosing Spondylitis

https://www.hindawi.com/journals/ecam/2020/4593412/

https://www.ncbi.nlm.nih.gov/pubmed/32508948?dopt=Abstract

TITLE:
Efficacy and Safety of Sinomenine Preparation for Ankylosing Spondylitis: A Systematic Review and Meta-Analysis of Clinical Randomized Controlled Trials.

DESCRIPTION:
Efficacy and Safety of Sinomenine Preparation for Ankylosing Spondylitis: A Systematic Review and Meta-Analysis of Clinical Randomized Controlled Trials.

Evid Based Complement Alternat Med. 2020;2020:4593412

Authors: Lin SS, Liu CX, Zhang JH, Wang H, Zhai JB, Mao JY, Wang XL

Abstract

Objectives: To systematically evaluate the efficacy and safety of sinomenine preparation (SP) for treating ankylosing spondylitis (AS).

Methods: Clinical randomized controlled trials (RCTs) of SP for treating AS were systematically identified in six electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang Databases from the inception up to 31 October 2019. Cochrane’s risk of bias tool was used to assess the methodological quality and Review Manager 5.3 software was used to analyze data.

Results: A total of 12 RCTs involving 835 patients were finally included. According to interventions, RCTs were divided into two types. The intervention in 10 RCTs was SP combined with conventional pharmacotherapy (CPT) versus CPT and that in 2 RCTs was SP alone versus CPT. The results of the meta-analysis showed that, compared with CPT alone, SP combined with oral CPT has better improvement in BASDAI (WMD = -1.84, 95% CI [-3.31, -0.37], P=0.01), morning stiffness time (WMD = -13.46, 95% CI [-16.12, -10.79], P < 0.00001), the Schober test (WMD = 1.26, 95% CI [0.72, 1.80], P < 0.00001), the occipital wall test (WMD = -0.55, 95% CI [-0.96, -0.14], P=0.009), the finger-to-ground distance (WMD = -3.28, 95% CI [-5.64, -0.93], P=0.006), 15 m walking time (WMD = -8.81, 95% CI [-13.42, -4.20], P=0.0002), the C-reactive protein (CRP) (WMD = -1.84, 95% CI [-3.24, -0.45], P=0.01), and the total effective rate (RR = 1.10, 95% CI [1.01, 1.20], P=0.03). Besides, it also showed that oral SP alone may be more effective in improving morning stiffness time (WMD = -31.89, 95% CI [-34.91, -28.87], P < 0.00001) compared with CPT alone. However, this study cannot provide evidence that loading the injectable SP based on CPT can significantly increase the efficacy due to the insufficient number of studies included. In terms of adverse events, there was no statistically significant difference between the experimental group and the control group. Conclusions: This study shows that oral SP may be effective and safe in the treatment of AS. Due to the low methodological quality of the included RCTs and the limitations of the meta-analysis, it is still necessary to carry out more multicenter, large-sample, and high-quality RCTs to further verify the conclusions. The review protocol was registered on PROSPERO (CRD42018099170), and the review was constructed following the PRISMA guidelines (Annex 1). PMID: 32508948 [PubMed] PMID: PubMed:32508948 DATE FOUND: 06/09/20 06:19AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32508948?dopt=Abstract

Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data

https://www.dovepress.com/therapeutic-potential-of-ixekizumab-in-the-treatment-of-ankylosing-spo-peer-reviewed-fulltext-article-TCRM

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170548/

https://www.ncbi.nlm.nih.gov/pubmed/32368068?dopt=Abstract

TITLE:
Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data.

DESCRIPTION:
Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data.

Ther Clin Risk Manag. 2020;16:287-297

Authors: Benucci M, Damiani A, Li Gobbi F, Grossi V, Infantino M, Manfredi M, Niccoli L, Cantini F

Abstract

Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 (Il-17), constituted the rationale to develop biologics selectively inhibiting these pathways. For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. Recent knowledge of the pathophysiology of spondyloarthritis has highlighted the emerging role of the IL-17/IL-23 axis. New therapies with selective biological drugs have emerged in the treatment of this pathology. In this review, we evaluated the effects of ixekizumab, a new anti-IL-17A, that was licensed both by EMA and FDA in August 2019 for the treatment of ankylosing spondylitis. The review highlights the efficacy and safety data of the 3 randomized controlled trials (COAST V-COAST W-COAST X) and those of the extension to 52 weeks of COAST V and COAST W.

PMID: 32368068 [PubMed]

PMID:
PubMed:32368068

DATE FOUND:
05/06/20 06:30AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32368068?dopt=Abstract

Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study

https://ard.bmj.com/content/early/2020/04/05/annrheumdis-2020-216980

https://www.ncbi.nlm.nih.gov/pubmed/32253184?dopt=Abstract

TITLE:
Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study.

DESCRIPTION:
Related Articles

Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study.

Ann Rheum Dis. 2020 Apr 06;:

Authors: van der Heijde D, Gensler LS, Deodhar A, Baraliakos X, Poddubnyy D, Kivitz A, Farmer MK, Baeten D, Goldammer N, Coarse J, Oortgiesen M, Dougados M

Abstract

OBJECTIVES: Bimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).

METHODS: Adults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data).

RESULTS: 303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%-46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6-5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab. CONCLUSIONS: Bimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies. TRIAL REGISTRATION NUMBER: NCT02963506. PMID: 32253184 [PubMed - as supplied by publisher] PMID: PubMed:32253184 DATE FOUND: 04/08/20 06:59AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32253184?dopt=Abstract

Therapeutic, diagnostic significance, and prognostic value of dickkopf-related protein-1 (DKK-1) and tumor necrosis factor-α (TNF-α) in ankylosing spondylitis

https://www.wjgnet.com/2307-8960/full/v8/i7/1213.htm

https://www.ncbi.nlm.nih.gov/pubmed/32337195?dopt=Abstract

TITLE:
Clinical significance and prognostic value of tumor necrosis factor-α and dickkopf related protein-1 in ankylosing spondylitis.

DESCRIPTION:
Related Articles

Clinical significance and prognostic value of tumor necrosis factor-α and dickkopf related protein-1 in ankylosing spondylitis.

World J Clin Cases. 2020 Apr 06;8(7):1213-1222

Authors: Xiong JH, Liu J, Chen J

Abstract

BACKGROUND: Ankylosing spondylitis (AS) frequently occurs in people aged 30-45 years, and its prevalence is generally believed to be between 0.1% and 1.4% globally. At present, the “gold standard” for diagnosis of AS requires the provision of pelvic X-rays, which makes it more difficult to perform in population-based epidemiological studies. Therefore, the identification of serological indicators related to the diagnosis, treatment, and prognosis of AS patients is of great significance.

AIM: To analyze the therapeutic, diagnostic significance and prognostic value of dickkopf-related protein-1 (DKK-1) and tumor necrosis factor-α (TNF-α) in AS.

METHODS: A total of 113 patients with active AS were selected as the research group, and 100 healthy subjects who underwent physical examination were selected as the control group. The levels of DKK-1 and TNF-α in peripheral blood in the two groups were compared. The diagnostic and predictive values of DKK-1 and TNF-α for AS were analyzed with ROC curves, and the factors influencing AS recurrence were analyzed with COX regression.

RESULTS: Before treatment, the research group showed lower DKK-1 levels but higher TNF-α levels than the control group (both a P < 0.05). In the research group, DKK-1 was up-regulated and TNF-α was down-regulated after 12 wk of treatment (a P < 0.05). The area under the curve, sensitivity and specificity of DKK-1 combined with TNF-α for diagnosing AS were 0.934, 82.30% and 97.00%, respectively. Before treatment, the area under the curve, cutoff value, sensitivity and specificity of DKK-1 for predicting the curative effect were 0.825, 68.42 pg/mL, 73.68% and 80.00%, respectively, and those of TNF-α were 0.863, 32.79 ng/L, 92.11% and 77.33%, respectively. DKK-1 and TNF-α levels after treatment were closely related to the curative effect (a P < 0.05). C-reactive protein, the Bath Ankylosing Spondylitis Disease Activity Index, DKK-1, and TNF-α were risk factors for AS recurrence (a P < 0.05). CONCLUSION: DKK-1 and TNF-α are effective in the diagnosis and treatment of AS and are risk factors for its recurrence. In addition, DKK-1 may be a potential target for the diagnosis of AS. PMID: 32337195 [PubMed] PMID: PubMed:32337195 DATE FOUND: 04/28/20 06:14AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32337195?dopt=Abstract

Janus Kinase Inhibitors: State of the Art in Clinical Use and Future Perspectives

https://www.ncbi.nlm.nih.gov/pubmed/32219519?dopt=Abstract

[Janus Kinase Inhibitors : State of the Art in Clinical Use and Future Perspectives]

TITLE:
[Janus kinase inhibitors : State of the art in clinical use and future perspectives].

DESCRIPTION:
Related Articles

[Janus kinase inhibitors : State of the art in clinical use and future perspectives].

Z Rheumatol. 2020 Mar 26;:

Authors: Alten R, Mischkewitz M, Stefanski AL, Dörner T

Abstract

BACKGROUND: Cytokines and associated intracellular signal cascades play a major role in the pathogenesis of autoimmune diseases. Janus kinases (JAK) are part of these intracellular signal transduction processes. A relatively new drug group of targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) are JAK inhibitors (JAKi) and are a promising treatment approach for autoimmune diseases.

EFFICACY: Hitherto, three JAKis, Tofacitinib, Baricitinib and Upadacitinib, have been approved for treatment of Rheumatoid Arthritis (RA) in the USA, Switzerland and the EU. Filgotinib, another JAKi, also showed promising results in the treatment of RA. Furthermore, tofacitinib received approval for the treatment of ulcerative colitis and psoriatic arthritis. In addition to the JAKis already mentioned, several other JAKis, e.g. filgotinib and peficitinib, are being and were investigated in various studies on indications, such as atopic dermatitis, ankylosing spondylitis and systemic lupus erythematosus.

SAFETY: Being immunosuppressants, JAKis show an elevated incidence of severe infections, comparable to biologics. The increased reactivation of varicella zoster virus is especially noteworthy. Under JAKi treatment cytopenia is also more frequent. Lymphopenia under JAKi treatment is of particular clinical relevance because of its association with an increase in the number of severe infections. Furthermore, an elevated risk of thromboembolic events, particularly pulmonary embolism has been noted. The risks concerning metabolic alterations and the occurrence of malignant neoplasms are comparable to those under treatment with biologics.

PMID: 32219519 [PubMed – as supplied by publisher]

PMID:
PubMed:32219519

DATE FOUND:
03/29/20 06:29AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32219519?dopt=Abstract

Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis

https://www.ncbi.nlm.nih.gov/pubmed/32219620?dopt=Abstract

https://link.springer.com/article/10.1007%2Fs10067-020-05032-4

TITLE:
Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis.

DESCRIPTION:
Related Articles

Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis.

Clin Rheumatol. 2020 Mar 26;:

Authors: Zhang F, Ma C, Zhang B, Bi L

Abstract

OBJECTIVES: This study aimed to investigate the relationship among smoking, TNF-α-blocker therapy, and the dynamic changes in gut microbiota in patients with ankylosing spondylitis (AS).

METHODS: Using a 16S rRNA sequence, 98 fecal samples of 20 AS patients collected after 0, 1, 3 and 6 months of anti-TNF-α treatment and from 20 matched health controls were examined. The variation in composition, abundance, and diversity of gut microbiota was analyzed. The dynamic effects of smoking and treatment on gut microbiota and therapeutic efficacy in AS patients were studied.

RESULTS: The increased relative abundance of microbiota in AS nonsmokers was g_Comamonas and g_Desulfovibrio, while that in AS smokers was g_Actinomyces, g_Collinsella, g_Lachnospiraceae_UCG-008, and g_Paraprevotella. The relative abundance of gut microbiota showed dynamic variation. The improvement rate of ASDAS in AS nonsmokers was higher than that in AS smokers (2.297 vs 1.736) after anti-TNF-α treatment. The β-diversity of gut microbiota in AS smokers was lower than that in AS nonsmokers and improved with treatment.

CONCLUSIONS: Both smoking and TNF-α-blocker had significant effects on the composition, relative abundance, and diversity of gut microbiota in AS patients. The AS smokers characteristically shared g_Collinsella and g_Dorea. The relative abundance of gut microbiota revealed high variability and was in dynamic fluctuation during treatment. The response of gut microbiota to anti-TNF-α treatment was found to be heterogeneous and selective. AS nonsmokers showed a greater improvement rate of ASDAS-CRP with treatment than AS smokers did. The AS smokers showed a lower β-diversity of gut microbiota, and improved after treatment.Key Points• Characterized the dynamic variation in gut microbiota in AS patients classified as smokers and nonsmokers during treatment with anti-TNF-α.• Confirmed the interaction between smoking, anti-TNF-α therapy, and gut microbiota.

PMID: 32219620 [PubMed – as supplied by publisher]

PMID:
PubMed:32219620

DATE FOUND:
03/29/20 06:18AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32219620?dopt=Abstract

Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS)

https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02149-4

https://www.ncbi.nlm.nih.gov/pubmed/32188494?dopt=Abstract

TITLE:
Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS).

DESCRIPTION:
Related Articles

Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS).

Arthritis Res Ther. 2020 Mar 18;22(1):51

Authors: Lin A, Inman RD, Streutker CJ, Zhang Z, Pritzker KPH, Tsui HW, Tsui FWL

Abstract

BACKGROUND: Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis.

METHODS: Baseline colonic pathology was conducted in the ank/ank mouse model. Serum lipocalin 2 was analyzed by ELISA, in ank/ank mutants versus C3FeB6-A/Aw-jwt/wt, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the ank/ank mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was examined by real-time PCR. Intraperitoneal injection was done with the PPARγ agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day.

RESULTS: This study showed that the ank/ank mice with fully fused spines had concurrent colonic inflammation. By first using the ank/ank mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the ank/ank mouse model involving PPARγ. Colonic expression of PPARγ was negatively associated with the degree of gut inflammation. The PPARγ agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPARγ in the aberrant expression of lipocalin 2.

CONCLUSIONS: In summary, lipocalin 2 modulated by PPARγ could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.

PMID: 32188494 [PubMed – in process]

PMID:
PubMed:32188494

DATE FOUND:
03/20/20 06:26AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32188494?dopt=Abstract

TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis

https://www.jci.org/articles/view/126567

https://www.ncbi.nlm.nih.gov/pubmed/32149730?dopt=Abstract

TITLE:
TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.

DESCRIPTION:
TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.

J Clin Invest. 2020 Mar 09;:

Authors: Gracey E, Hromadová D, Lim M, Qaiyum Z, Zeng M, Yao Y, Srinath A, Baglaenko Y, Yeremenko N, Westlin W, Masse C, Müller M, Strobl B, Miao W, Inman RD

Abstract

Spondyloarthritis (SpA) represents a family of inflammatory diseases of the spine and peripheral joints. Ankylosing spondylitis (AS) is the prototypic form of SpA in which progressive disease can lead to fusion of the spine. Therapeutically, knowledge of type 3 immunity has translated into the development of IL-23- and IL-17A-blocking antibodies for the treatment of SpA. Despite being able to provide symptomatic control, the current biologics do not prevent the fusion of joints in AS patients. Thus, there is an unmet need for disease-modifying drugs. Genetic studies have linked the Janus kinase TYK2 to AS. TYK2 is a mediator of type 3 immunity through intracellular signaling of IL-23. Here, we describe and characterize a potentially novel small-molecule inhibitor of TYK2 that blocked IL-23 signaling in vitro and inhibited disease progression in animal models of SpA. The effect of the inhibitor appears to be TYK2 specific, using TYK2-inactive mice, which further revealed a duality in the induction of IL-17A and IL-22 by IL-23. Specifically, IL-22 production was TYK2/JAK2/STAT3 dependent, while IL-17A was mostly JAK2 dependent. Finally, we examined the effects of AS-associated TYK2 SNPs on TYK2 expression and function and correlated them with AS disease progression. This work provides evidence that TYK2 inhibitors have great potential as an orally delivered therapeutic for SpA.

PMID: 32149730 [PubMed – as supplied by publisher]

PMID:
PubMed:32149730

DATE FOUND:
03/10/20 06:19AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32149730?dopt=Abstract

TNF Receptor:Fc Fusion Protein (rhTNFR:Fc) suppresses inflammation and bone destruction of ankylosing spondylitis by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway

https://www.ncbi.nlm.nih.gov/pubmed/32116188?dopt=Abstract

http://www.eurekaselect.com/179845/article

TITLE:
TNF Receptor:Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis.

TNF Receptor:Fc Fusion Protein (rhTNFR:Fc) suppresses inflammation and bone destruction of Ankylosing Spondylitis

DESCRIPTION:
TNF Receptor:Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis.

Curr Pharm Biotechnol. 2020 Mar 01;:

Authors: Zhang P, Zhou S, Chen Z, Tian Y, Wang Q, Li H, Zhang T, Guo Q, Wang M, Guo C

Abstract

BACKGROUND: Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active ankylosing spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However, the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR:Fc treatment.

METHODS: Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG), essential molecules for osteoclast differentiation, were studied in AS before and after treatment. Further, proliferation of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16) were measured in vitro.

RESULTS: Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio, CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between CXCL16 levels and polymerase chain reaction results (P<0.001). CONCLUSIONS: Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway. PMID: 32116188 [PubMed - as supplied by publisher] PMID: PubMed:32116188 DATE FOUND: 03/03/20 07:06AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32116188?dopt=Abstract

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis

https://link.springer.com/article/10.1007%2Fs10067-020-04970-3

https://www.ncbi.nlm.nih.gov/pubmed/32107666?dopt=Abstract

TITLE:
A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis.

DESCRIPTION:
Related Articles

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis.

Clin Rheumatol. 2020 Feb 27;:

Authors: Deodhar A, Chakravarty SD, Cameron C, Peterson S, Hensman R, Fogarty S, Spin P, Kafka S, Nair S, Gensler LS

Abstract

OBJECTIVE: To compare the relative efficacy of current and investigational biologic and oral small molecule (OSM) treatments for active ankylosing spondylitis (AS).

METHODS: A systematic literature review was conducted to identify all phase 2/3 randomized trials of interest in patients with AS. Outcomes assessed were ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) and C-reactive protein (CRP) at weeks 12-16. Bayesian network meta-analyses were conducted for outcomes using a random effects model. Baseline-risk adjustment was also conducted to account for differences in placebo response across studies. Surface Under the Cumulative Ranking curve (SUCRA) values are reported, reflecting the relative probability that intervention was the best of all interventions.

RESULTS: The investigational agent tofacitinib 5 mg was the top-ranked treatment (SUCRA, 93%) for ASAS20 response, followed by intravenous (IV) golimumab 2 mg/kg (90%). Golimumab IV 2 mg/kg and infliximab 5 mg/kg were the top two ranked treatments for change from baseline in BASFI (golimumab IV, 81%; infliximab, 80%) and change from baseline in CRP (infliximab, 90%; golimumab IV, 82%).

CONCLUSIONS: Two approved therapies (golimumab IV, infliximab) and one investigational product ranked highest for efficacy in AS.Key Points• Although golimumab IV, infliximab, and tofacitinib ranked highest for efficacy in AS, differences in efficacy between approved and investigational therapies were not statistically significant.

PMID: 32107666 [PubMed – as supplied by publisher]

PMID:
PubMed:32107666

DATE FOUND:
02/29/20 06:36AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32107666?dopt=Abstract

Is Any Correlation Present Between the Severity of Syndesmophytes and Spinopelvic and Clinical Parameters in Advanced Ankylosing Spondylitis?

https://www.sciencedirect.com/science/article/abs/pii/S1878875020303624?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/32105868?dopt=Abstract

TITLE:
Is Any Correlation Present Between the Severity of Syndesmophytes and Spinopelvic and Clinical Parameters in Advanced Ankylosing Spondylitis?

DESCRIPTION:
Related Articles

Is Any Correlation Present Between the Severity of Syndesmophytes and Spinopelvic and Clinical Parameters in Advanced Ankylosing Spondylitis?

World Neurosurg. 2020 05;137:e618-e625

Authors: Liu GP, Qian BP, Qiu Y, Huang JC, Qiao M, Wang B

Abstract

OBJECTIVE: The present study evaluated the severity of syndesmophytes and its correlation with the spinopelvic and clinical outcomes in patients with ankylosing spondylitis (AS).

METHODS: The data from 41 consecutive patients with AS who had undergone pedicle subtraction osteotomy surgery at our institution were reviewed. The computed tomography syndesmophyte score (CTSS), a novel method of evaluating the severity of syndesmophytes, was applied to assess the syndesmophytes of the whole, cervical, thoracic, and lumbar spine. The measured spinopelvic parameters included global kyphosis, sagittal vertical axis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. The Oswestry disability index questionnaire, C-reactive protein, and erythrocyte sedimentation rate were used to evaluate the clinical outcome. The Pearson correlation test was performed to identify correlations between syndesmophyte severity and the spinopelvic and clinical parameters.

RESULTS: The Pearson correlation analysis demonstrated that the whole CTSS (WCTSS), cervical CTSS, thoracic CTSS, and lumbar CTSS (LCTSS) correlated significantly with each other (P < 0.05). All the CTSSs correlated positively with age, disease duration, and pelvic tilt (P < 0.05). In addition, both sagittal vertical axis and lumbar lordosis were significantly related to the WCTSS, cervical CTSS, and LCTSS (P < 0.05). The Oswestry disability index correlated negatively with the WCTSS (r = -0.312; P < 0.05), thoracic CTSS (r = -0.314; P < 0.05), and LCTSS (r = -0.343; P < 0.05). CONCLUSIONS: In advanced AS, old age and a long disease duration are risk factors for the progression of syndesmophytes. The progression of syndesmophytes might contribute to spinal sagittal malalignment. With serious syndesmophytes, pelvic retroversion seems to be the major compensatory mechanism for spinal sagittal malalignment. PMID: 32105868 [PubMed - indexed for MEDLINE] PMID: PubMed:32105868 DATE FOUND: 08/18/20 07:22AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/32105868?dopt=Abstract

Huangqin Qingre Chubi Capsules (HQC) improves clinical symptoms and oxidative stress of ankylosing spondylitis patients via activating PPARγ mediated AMPK/FOXO3a pathway

https://www.ncbi.nlm.nih.gov/pubmed/32237331?dopt=Abstract

http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.19540/j.cnki.cjcmm.20190619.501

TITLE:
[Huangqin Qingre Chubi Capsules in improving oxidative stress of patients with ankylosing spondylitis via activating PPARγ mediated AMPK/FOXO3a pathway].

Huangqin Qingre Chubi Capsule activates PPARγ-mediated AMPK / FOXO3a signaling pathway to improve oxidative stress in patients with ankylosing spondylitis

DESCRIPTION:
Related Articles

[Huangqin Qingre Chubi Capsules in improving oxidative stress of patients with ankylosing spondylitis via activating PPARγ mediated AMPK/FOXO3a pathway].

Zhongguo Zhong Yao Za Zhi. 2020 Jan;45(2):451-456

Authors: Huang D, Liu J, Zong RK, Wan L

Abstract

To investigate the efficacy of Huangqin Qingre Chubi Capsules(HQC) in patients with ankylosing spondylitis(AS) and its effect on oxidative stress, and to explore its possible mechanism. Fifty-eight cases of AS patients were randomly divided into HQC group and salazosulfapyridine(SASP) group. Another 30 healthy people were employed as a control group. Superoxide dismutase(SOD), total antioxidant capacity(TAOC), malondialdehyde(MDA), lipid peroxidatio(LPO), interleukin-1β(IL-1β), IL-10, IL-4, and tumor necrosis factor-α(TNF-α) were detected by ELISA. The mRNA expression levels of AMP-activated protein kinase(AMPK-α), forkhead box O3a(FOXO3a), manganese superoxide dismutase(MnSOD), and peroxisome proliferator-activated receptor gamma(PPARγ) were detected by Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expression levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, and PPARγ were detected by Western blot. A questionnaire was used to evaluate the disease activity score and observe the clinical efficacy of HQC in AS patients. The levels of MDA, LPO, TNF-α, and IL-1β were significantly increased in the peripheral blood of AS patients, and SOD, TAOC, IL-4, IL-10 levels were significantly decreased. After HQC treatment, scores of disease active indexes were all decreased, and its clinical efficacy was significantly higher than that in SASP group. After HQC treatment, TAOC, SOD, IL-4, IL-10 were increased and MDA, LPO, TNF-α, IL-1β were decreased; mRNA levels of AMPK-α, FOXO3a, MnSOD, PPARγ and protein levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, PPARγ were increased(P<0.01 or P<0.05). HQC can effectively improve the clinical symptoms and oxidative stress of AS patients, and its mechanism may be related to activating PPARγ and up-regulating AMPK/FOXO3a signal pathway.

PMID: 32237331 [PubMed – in process]

PMID:
PubMed:32237331

DATE FOUND:
04/03/20 06:42AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32237331?dopt=Abstract

Improvement of conjunctival cytological grade and tear production in Ankylosing Spondylitis patients under TNF inhibitors: a long-term follow-up

https://www.nature.com/articles/s41598-019-57266-1

https://pubmed.ncbi.nlm.nih.gov/31942038-improvement-of-conjunctival-cytological-grade-and-tear-production-in-ankylosing-spondylitis-patients-under-tnf-inhibitors-a-long-term-follow-up/?from_term=ankylosing+spondylitis&from_sort=date&from_size=200&from_pos=1

Improvement of conjunctival cytological grade and tear production in Ankylosing Spondylitis patients under TNF inhibitors: a long-term follow-up

Fany Solange Usuba, Carla Gonçalves Schahin Saad, Nadia Emi Aikawa, Priscila Novaes, Julio Cesar Bertacini Moraes, Ruth Miyuki Santo, Jozelio Freire Carvalho, Eloisa Bonfá & Milton Ruiz Alves

IL-23 and IL-17 cytokine levels might be an important factor in ankylosing spondylitis (AS) patients who are unresponsive to biologics

http://kjim.org/journal/view.php?doi=10.3904/kjim.2018.364

https://pubmed.ncbi.nlm.nih.gov/31830775-effect-of-biologics-in-the-level-of-cytokines-in-the-synovial-fluid-of-patients-with-ankylosing-spondylitis/

Effect of biologics in the level of cytokines in the synovial fluid of patients with ankylosing spondylitis.

IL-23 and IL-17 cytokine levels might be an important factor in ankylosing spondylitis (AS) patients who are unresponsive to biologics

Abstract
Background/aims: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs.

Methods: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups.

Results: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group.

Conclusions: Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.

Keywords: Arthritis, rheumatoid; Interleukins; Spondylitis, ankylosing; Synovial fluid.

Notoginsenoside R1 suppresses miR-301a via NF-κB pathway in lipopolysaccharide-treated ATDC5 cells

https://www.sciencedirect.com/science/article/pii/S0014480019303582?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31837326?dopt=Abstract

TITLE:
Notoginsenoside R1 suppresses miR-301a via NF-κB pathway in lipopolysaccharide-treated ATDC5 cells.

DESCRIPTION:
Related Articles

Notoginsenoside R1 suppresses miR-301a via NF-κB pathway in lipopolysaccharide-treated ATDC5 cells.

Exp Mol Pathol. 2020 02;112:104355

Authors: Dong Y, Yan X, Yang X, Yu C, Deng Y, Song X, Zhang L

Abstract

BACKGROUND: Notoginsenoside R1 (NG-R1) exhibits a pharmacological activity against excessive inflammation. Here, we aimed to ascertain the anti-inflammatory role of NG-R1 in ankylosing spondylitis (AS) as well as the possible mechanism which is still under to be elucidated.

METHODS: In this study, lipopolysaccharide (LPS) was applied to evoke extreme inflammation in ATDC5 cells. To investigate the anti-inflammatory property of NG-R1, ATDC5 cells were exposed to NG-R1 prior to LPS stimulation. microRNA-301a (miR-301a)-overexpressed ATDC5 cells were established which confirmed by qRT-PCR. Then, inflammatory lesions were indicated by cell viability, apoptosis and inflammatory factors, including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). Nuclear factor-kappa B (NF-κB) pathway was determined by Western blotting assay.

RESULTS: We found NG-R1 dramatically dampened the decrease of cell viability, facilitation of apoptosis and abundance of inflammatory factors induced by LPS. Additionally, NG-R1 pre-incubation impeded LPS-induced accumulation of miR-301a. However, the protective capacity of NG-R1 was impaired by miR-301a overexpression. Of note, LPS-caused phosphorylation of p65 and inhibitor of nuclear factor kappa-B alpha (IκBα) was repressed by NG-R1, while further enhanced in miR-301-transfected ATDC5 cells.

CONCLUSION: NG-R1 relived LPS-elicited inflammatory damages via blocking NF-κB in a miR-301a-silenced manner.

PMID: 31837326 [PubMed – indexed for MEDLINE]

PMID:
PubMed:31837326

DATE FOUND:
07/16/20 06:57AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31837326?dopt=Abstract

Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis

https://www.sciencedirect.com/science/article/pii/S0896841119306377?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31806420?dopt=Abstract

TITLE:
Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

DESCRIPTION:
Related Articles

Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

J Autoimmun. 2019 Dec 02;:102360

Authors: Zhou C, Zhao H, Xiao XY, Chen BD, Guo RJ, Wang Q, Chen H, Zhao LD, Zhang CC, Jiao YH, Ju YM, Yang HX, Fei YY, Wang L, Shen M, Li H, Wang XH, Lu X, Yang B, Liu JJ, Li J, Peng LY, Zheng WJ, Zhang CY, Zhou JX, Wu QJ, Yang YJ, Su JM, Shi Q, Wu D, Zhang W, Zhang FC, Jia HJ, Liu DP, Jie ZY, Zhang X

Abstract

OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota.

METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet’s disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay.

RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen.

CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

PMID: 31806420 [PubMed – as supplied by publisher]

PMID:
PubMed:31806420

DATE FOUND:
12/07/19 06:24AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31806420?dopt=Abstract

HLA-B27-mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis

https://www.jci.org/articles/view/125212

https://www.ncbi.nlm.nih.gov/pubmed/31682238?dopt=Abstract

TITLE:
HLA-B27-mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis.

DESCRIPTION:
HLA-B27-mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis.

J Clin Invest. 2019 Nov 04;:

Authors: Liu CH, Raj S, Chen CH, Hung KH, Chou CT, Chen IH, Chien JT, Lin IY, Yang SY, Angata T, Tsai WC, Wei JC, Tzeng IS, Hung SC, Lin KI

Abstract

Ankylosing spondylitis (AS) is a type of axial inflammation. Over time, some patients develop spinal ankylosis and permanent disability; however, current treatment strategies cannot arrest syndesmophyte formation completely. Here, we used mesenchymal stem cells (MSCs) from AS patients (AS MSCs) within the enthesis involved in spinal ankylosis to delineate that the HLA-B27-mediated spliced X-box-binding protein 1 (sXBP1)/retinoic acid receptor-β (RARB)/tissue-nonspecific alkaline phosphatase (TNAP) axis accelerated the mineralization of AS MSCs, which was independent of Runt-related transcription factor 2 (Runx2). An animal model mimicking AS pathological bony appositions was established by implantation of AS MSCs into the lumbar spine of NOD-SCID mice. We found that TNAP inhibitors, including levamisole and pamidronate, inhibited AS MSC mineralization in vitro and blocked bony appositions in vivo. Furthermore, we demonstrated that the serum bone-specific TNAP (BAP) level was a potential prognostic biomarker to predict AS patients with a high risk for radiographic progression. Our study highlights the importance of the HLA-B27-mediated activation of the sXBP1/RARB/TNAP axis in AS syndesmophyte pathogenesis and provides a new strategy for the diagnosis and prevention of radiographic progression of AS.

PMID: 31682238 [PubMed – as supplied by publisher]

PMID:
PubMed:31682238

DATE FOUND:
11/05/19 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31682238?dopt=Abstract

Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis

https://ard.bmj.com/content/early/2019/11/03/annrheumdis-2019-216118

https://www.ncbi.nlm.nih.gov/pubmed/31685553?dopt=Abstract

TITLE:
Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W).

DESCRIPTION:
Related Articles

Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W).

Ann Rheum Dis. 2019 Nov 04;:

Authors: Dougados M, Wei JC, Landewé R, Sieper J, Baraliakos X, Van den Bosch F, Maksymowych WP, Ermann J, Walsh JA, Tomita T, Deodhar A, van der Heijde D, Li X, Zhao F, Bertram CC, Gallo G, Carlier H, Gensler LS, COAST-V and COAST-W Study Groups

Abstract

OBJECTIVES: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).

METHODS: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.

RESULTS: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.

CONCLUSION: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.

TRIAL REGISTRATION NUMBER: NCT02696785/NCT02696798.

PMID: 31685553 [PubMed – as supplied by publisher]

PMID:
PubMed:31685553

DATE FOUND:
11/07/19 01:54PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31685553?dopt=Abstract

Potential utility of anti-TNF drugs in synovial chondromatosis associated with ankylosing spondylitis

https://onlinelibrary.wiley.com/doi/abs/10.1111/1756-185X.13734

https://www.ncbi.nlm.nih.gov/pubmed/31647182?dopt=Abstract

TITLE:
Potential utility of anti-TNF drugs in synovial chondromatosis associated with ankylosing spondylitis.

DESCRIPTION:
Potential utility of anti-TNF drugs in synovial chondromatosis associated with ankylosing spondylitis.

Int J Rheum Dis. 2019 Oct 24;:

Authors: Yu S, Wu M, Zhou G, Ishikawa T, Liang J, Nallapothula D, Singh RR, Wang Q, Wang M

Abstract

We describe a previously unreported association of ankylosing spondylitis with synovial chondromatosis, and briefly review previously reported cases and treatment of synovial chondromatosis in patients with other immune-mediated inflammatory arthritides. A 20-year-old man with ankylosing spondylitis whose axial disease was in remission with nonsteroidal anti-inflammatory drugs and oral disease-modifying anti-rheumatic drugs developed recurrent right knee pain and swelling. Magnetic resonance imaging of his right knee revealed calcified loose bodies, suggestive of synovial chondromatosis. While waiting for the surgical intervention and other invasive therapy previously reported in patients with synovial chondromatosis, a trial of etanercept eliminated the pain and swelling of the knee; however, the loose bodies have persisted during the 2-year follow-up. Thus, synovial chondromatosis should be considered in the differential diagnoses of a refractory monoarticular pain and swelling in patients with otherwise controlled inflammatory arthritis. Our report advocates a trial of anti-tumor necrosis factor drugs, which might delay the need for invasive therapy in patients with synovial chondromatosis.

PMID: 31647182 [PubMed – as supplied by publisher]

PMID:
PubMed:31647182

DATE FOUND:
10/25/19 06:59PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31647182?dopt=Abstract

Advances in nanomedicine for the treatment of ankylosing spondylitis

https://www.dovepress.com/advances-in-nanomedicine-for-the-treatment-of-ankylosing-spondylitis-peer-reviewed-fulltext-article-IJN

https://www.ncbi.nlm.nih.gov/pubmed/31806960?dopt=Abstract

TITLE:
Advances in nanomedicine for the treatment of ankylosing spondylitis.

DESCRIPTION:
Related Articles

Advances in nanomedicine for the treatment of ankylosing spondylitis.

Int J Nanomedicine. 2019;14:8521-8542

Authors: Xi Y, Jiang T, Chaurasiya B, Zhou Y, Yu J, Wen J, Shen Y, Ye X, Webster TJ

Abstract

Ankylosing spondylitis (AS) is a complex disease characterized by inflammation and ankylosis primarily at the cartilage-bone interface. The disease is more common in young males and risk factors include both genetic and environmental. While the pathogenesis of AS is not completely understood, it is thought to be an immune-mediated disease involving inflammatory cellular infiltrates, and human leukocyte antigen-B27. Currently, there is no specific diagnostic technique available for this disease; therefore conventional diagnostic approaches such as clinical symptoms, laboratory tests and imaging techniques are used. There are various review papers that have been published on conventional treatment approaches, and in this review work, we focus on the more promising nanomedicine-based treatment modalities to move this field forward.

PMID: 31806960 [PubMed – in process]

PMID:
PubMed:31806960

DATE FOUND:
12/07/19 07:53AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31806960?dopt=Abstract

Anti-TNF-α therapy alters the gut microbiota in proteoglycan-induced ankylosing spondylitis in mice

https://onlinelibrary.wiley.com/doi/full/10.1002/mbo3.927

https://www.ncbi.nlm.nih.gov/pubmed/31556231?dopt=Abstract

TITLE:
Anti-TNF-α therapy alters the gut microbiota in proteoglycan-induced ankylosing spondylitis in mice.

DESCRIPTION:
Related Articles

Anti-TNF-α therapy alters the gut microbiota in proteoglycan-induced ankylosing spondylitis in mice.

Microbiologyopen. 2019 Sep 26;:e927

Authors: Liu B, Yang L, Cui Z, Zheng J, Huang J, Zhao Q, Su Z, Wang M, Zhang W, Liu J, Wang T, Li Q, Lu H

Abstract

Ankylosing spondylitis is a chronic, progressive disease, and its treatment is relevant to the gut microbiota. Anti-tumor necrosis factor-alpha (anti-TNF-α) therapy alters the gut microbiota in many diseases, including inflammatory bowel disease. However, little is known about the effect of TNF-α blocker treatment on the gut microbiota in ankylosing spondylitis. Herein, the effect of a TNF-α blocker on the gut microbiota in proteoglycan-induced arthritis was investigated. Proteoglycan-induced mice were treated with an rhTNFR:Fc solution of etanercept (5 µg/g) for 4 weeks. rhTNFR:Fc treatment attenuated the arthritis incidence and severity of arthritis in the proteoglycan-induced mice and decreased inflammation in the ankle joints and ameliorated ileal tissue destruction. Moreover, high gut permeability occurred, and zonula occludens-1 and occludin protein levels were reduced in proteoglycan-induced mice. These levels were significantly restored by the administration of rhTNFR:Fc. The serum TNF-α and IL-17 levels were also decreased. In addition, flora analysis via 16S rDNA high-throughput sequencing revealed that rhTNFR:Fc treatment restored the gut microbiota composition to a composition similar to that in control mice. In conclusion, anti-TNF-α therapy attenuated proteoglycan-induced arthritis progression and modulated the gut microbiota and intestinal barrier function. These results provide new insights for anti-TNF-α therapy strategies via regulating the gut microbiota in ankylosing spondylitis.

PMID: 31556231 [PubMed – as supplied by publisher]

PMID:
PubMed:31556231

DATE FOUND:
09/27/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31556231?dopt=Abstract

Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference?

https://www.sciencedirect.com/science/article/pii/S1699258X19301160?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31558361?dopt=Abstract

TITLE:
Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference? An observational study.

DESCRIPTION:
Related Articles

Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference? An observational study.

Reumatol Clin. 2019 Sep 24;:

Authors: Moreno M, Arévalo M, Zamora M, Pontes C, Oliva JC, Gratacós J

Abstract

OBJECTIVE: To assess whether there are any real-life differences between ankylosing spondylitis (AS) patients treated with NSAID or TNF inhibitors (TNFi) regarding disease activity.

METHODS: This is an observational transversal unicentric study with retrospective retrieval of data from clinical records of all AS patients attended in our hospital. We compared clinical activity measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores between patients treated with NSAID and those treated with TNFi, in terms of low disease activity defined as BASDAI<4, and inactivity when BASDAI≤2. As secondary variables, we also collected epidemiological, clinical and radiological data from all those patients. RESULTS: A total of 152 AS patients (81% male), with an average age of 49.45±12.38 years and a disease duration of 13.5±9.79 years were included in the study. Eighty-nine patients (58.6%) were treated with NSAID and 63 (41.4%) with TNFi. The proportion of patients with low disease activity and inactive disease was significantly higher in the TNFi treatment group compared to the NSAID group (81 vs. 47, P=.0001) and (44 vs. 24, P=.007), respectively. Patients treated with NSAIDs also showed significantly more global pain and night pain than those under TNFi therapy. The BASFI score and especially the type of treatment (NSAID or TNFI) were the only variables independently associated with low disease activity or inactive disease. CONCLUSION: In real world practice, AS patients under TNFi treatment show a better control of clinical symptoms than those under NSAIDs. PMID: 31558361 [PubMed - as supplied by publisher] PMID: PubMed:31558361 DATE FOUND: 09/28/19 03:27PM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/31558361?dopt=Abstract

Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels

https://josr-online.biomedcentral.com/articles/10.1186/s13018-019-1322-7

https://www.ncbi.nlm.nih.gov/pubmed/31533751?dopt=Abstract

TITLE:
Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels.

DESCRIPTION:
Related Articles

Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels.

J Orthop Surg Res. 2019 Sep 18;14(1):313

Authors: Xu J, Deng Y, Yu CY, Gao ZM, Yang XR, Zhang Q, Zhang L

Abstract

BACKGROUND: This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF).

METHODS: One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA).

RESULTS: BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment. CONCLUSIONS: wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores. PMID: 31533751 [PubMed - in process] PMID: PubMed:31533751 DATE FOUND: 09/20/19 06:09AM LINK / URL: https://www.ncbi.nlm.nih.gov/pubmed/31533751?dopt=Abstract

miR-29a promotes osteoblast proliferation by downregulating DKK-1 expression and activating Wnt/β-catenin signaling pathway

http://www.advances.umed.wroc.pl/ahead-of-print/104533.pdf

https://www.ncbi.nlm.nih.gov/pubmed/31538414?dopt=Abstract

TITLE:
miR-29a promotes osteoblast proliferation by downregulating DKK-1 expression and activating Wnt/β-catenin signaling pathway.

DESCRIPTION:
Related Articles

miR-29a promotes osteoblast proliferation by downregulating DKK-1 expression and activating Wnt/β-catenin signaling pathway.

Adv Clin Exp Med. 2019 Sep 16;:

Authors: Zhang F, Cao K, Du G, Zhang Q, Yin Z

Abstract

BACKGROUND: MicroRNA (miRNA) is a kind of non-coding small RNA with a negative regulating function. Some miRNAs play a role in regulating the differentiation and function of osteoblasts, chondrocytes and osteoclasts.

OBJECTIVES: In this study, we analyzed the role of miR-29a and dickkopf-1 (DKK-1) in osteoblast differentiation.

MATERIAL AND METHODS: Specimens were collected from the surgical resection of pathological ankylosing spondylitis (AS) tissue and some normal tissues. The expression of miR-29a, DKK-1 and β-catenin in normal and AS tissues were detected with real-time polymerase chain reaction (RT-PCR) and western blotting. Cell proliferation was detected with a Cell Counting Kit-8, cell migration and invasion were determined using a Transwell system and cell apoptosis was analyzed with flow cytometry. The luciferase reporter gene plasmid pGL3-DKK-1 and a point-mutation of the luciferase reporter gene plasmid mut-pGL3-DKK-1 were constructed.

RESULTS: It was found that miR-29a could promote the proliferation of hFOB1.19 cells, while DKK-1 inhibited their proliferation. Also, miR-29a was able to inhibit the apoptosis of hFOB1.19 cells, while DKK-1 was able to promote the apoptosis of hFOB1.19 cells. When it comes to the invasion and migration of hFOB1.19 cells, miR-29a was found to promote it, while DKK-1 did not.

CONCLUSIONS: These findings will lead to a better understanding of the proliferation and differentiation of osteoblasts and will provide new insights for the treatment of this disease.

PMID: 31538414 [PubMed – as supplied by publisher]

PMID:
PubMed:31538414

DATE FOUND:
09/21/19 06:08AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31538414?dopt=Abstract

Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study

https://rmdopen.bmj.com/content/5/2/e001005

https://www.ncbi.nlm.nih.gov/pubmed/31565244?dopt=Abstract

TITLE:
Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study.

DESCRIPTION:
Related Articles

Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study.

RMD Open. 2019;5(2):e001005

Authors: Baraliakos X, Braun J, Deodhar A, Poddubnyy D, Kivitz A, Tahir H, Van den Bosch F, Delicha EM, Talloczy Z, Fierlinger A

Abstract

Objective: This study aimed to report end-of-study results on efficacy and safety of secukinumab 150 mg through 5 years in patients with ankylosing spondylitis (AS; MEASURE 1 extension trial (NCT01863732)).

Methods: After the 2-year core trial, 274 patients receiving subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) every 4 weeks were invited to enter the 3-year extension study. Dose escalation from 75 to 150 mg (approved dose) was allowed at or after week 156 based on the judgement of the treating physician. Assessments at week 260 (5 years) included Assessment of SpondyloArthritis international Society (ASAS) 20/40 and other efficacy outcomes. Data are presented as observed. Safety assessment included all patients who received ≥1 dose of study treatment.

Results: Of the 274 patients who entered the extension study, 84% (230/274) completed 5 years of treatment. ASAS20/40 responses were 78.6/65.2%, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response was 63.4% and mean (±SD) BASDAI total score was 2.6±1.76 with secukinumab 150 mg at 5 years. Improvements in efficacy outcomes were sustained through 5 years. A total of 82 patients on secukinumab 75 mg (56.2%) had their dose escalated to 150 mg after week 168; ASAS40, ASAS-PR, ASAS 5/6 and BASDAI50 responses were improved in patients whose dose was escalated from secukinumab 75 to 150 mg. Secukinumab was well tolerated with a safety profile consistent over the course of the study.

Conclusions: Secukinumab 150 mg provided sustained efficacy across multiple domains of AS with a favourable and consistent safety profile through 5-year treatment. Over 50% of patients required dose escalation from 75 to 150 mg and efficacy improved in these patients.

PMID: 31565244 [PubMed]

PMID:
PubMed:31565244

DATE FOUND:
10/01/19 06:05AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31565244?dopt=Abstract

Baseline Interleukin-6 and Erythrocyte Sedimentation Rate Can Predict Clinical Response of TNF Inhibitor Treatment in Patients with Ankylosing Spondylitis

https://www.ncbi.nlm.nih.gov/pubmed/31611204?dopt=Abstract

TITLE:
Baseline Interleukin-6 and Erythrocyte Sedimentation Rate Can Predict Clinical Response of TNF Inhibitor Treatment in Patients with Ankylosing Spondylitis.

DESCRIPTION:
Related Articles

Baseline Interleukin-6 and Erythrocyte Sedimentation Rate Can Predict Clinical Response of TNF Inhibitor Treatment in Patients with Ankylosing Spondylitis.

Ann Clin Lab Sci. 2019 Sep;49(5):611-618

Authors: Dong Y, Guo J, Bi L

Abstract

OBJECTIVE: The objective of this study is to investigate the baseline predictors of clinical response from tumor necrosis factor (TNF) inhibitor within ankylosing spondylitis (AS) patients.

METHODS: We selected 60 AS patients and 24 healthy individuals. The interleukin (IL)-1β, IL-6, IL-17A and TNF-α levels were measured using the cytometric bead array. The receiver operating characteristic curve was used to analyze the cut off values of baseline predictors. A binary logistic regression test was used to investigate the association between baseline predictors and clinical response.

RESULTS: At baseline, the IL-1β, IL-6 and TNF-α level were positively correlated with disease activity. After 12 weeks of treatment, good responders had lower baseline IL-6 level and erythrocyte sedimentation rate (ESR) than non/poor responders. The cut off value of baseline IL-6 level and ESR to predict clinical response of TNF inhibitor treatment were 9.05 pg/mL and 47.00 mm/h, respectively. Binary logistic regression found that baseline IL-6 levels and ESR had an adverse relationship with clinical response, and the combination of IL-6 level and ESR could predict clinical response more effectively.

CONCLUSIONS: The baseline IL-6 level and ESR can predict the clinical response of TNF inhibitor treatment within AS patients, which might facilitate the selection and adjustment of medication regimens for subjects.

PMID: 31611204 [PubMed – in process]

PMID:
PubMed:31611204

DATE FOUND:
10/16/19 06:05AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31611204?dopt=Abstract

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

https://onlinelibrary.wiley.com/doi/full/10.1002/art.41042

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.28901

https://pubmed.ncbi.nlm.nih.gov/31074089-the-effects-of-nanocurcumin-on-treg-cell-responses-and-treatment-of-ankylosing-spondylitis-patients-a-randomized-double-blind-placebo-controlled-clinical-trial/

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

LILR and KIR receptors recognize HLA-B27 and may influence immune response in ankylosing spondylitis (AS) development

https://onlinelibrary.wiley.com/doi/abs/10.1111/iji.12422

https://www.ncbi.nlm.nih.gov/pubmed/30892832?dopt=Abstract

TITLE:
The effect of LILRB1 but not LILRA3 gene polymorphism in immunopathology of ankylosing spondylitis-A parallel to KIR genes.

DESCRIPTION:
Related Articles

The effect of LILRB1 but not LILRA3 gene polymorphism in immunopathology of ankylosing spondylitis-A parallel to KIR genes.

Int J Immunogenet. 2019 Jun;46(3):146-151

Authors: Majorczyk E, Wiśniewski A, Zoń-Giebel A, Chlebicki A, Wiland P, Kuśnierczyk P

Abstract

LILR and KIR receptors recognize HLA-B27 and may influence immune response in ankylosing spondylitis (AS) development. Purpose of the study was to analyse LILRB1/LILRA3 polymorphisms in AS. We observed a possible protective effect of the T allele of LILRB1 rs1061680:T>C and no association with insertion/deletion polymorphisms of LILRA3 with AS.

PMID: 30892832 [PubMed – indexed for MEDLINE]

PMID:
PubMed:30892832

DATE FOUND:
10/08/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/30892832?dopt=Abstract

The safety and efficacy of Guluronic acid (G2013) in ankylosing spondylitis: could be appropriate for management of AS

https://www.sciencedirect.com/science/article/abs/pii/S1734114018304821?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31003148?dopt=Abstract

TITLE:
The safety and efficacy of Guluronic acid (G2013) in ankylosing spondylitis: A randomized controlled parallel clinical trial.

DESCRIPTION:
Related Articles

The safety and efficacy of Guluronic acid (G2013) in ankylosing spondylitis: A randomized controlled parallel clinical trial.

Pharmacol Rep. 2019 Jun;71(3):393-398

Authors: Nazeri S, Jamshidi AR, Mahmoudi M, Vojdanian M, Khadem Azarian S, Afraei S, Mostafaei S, Hosseini M, Mirshafiey A

Abstract

BACKGROUND: To assess the therapeutic efficacy, safety and tolerability of Guluronic acid (G2013) in patients with ankylosing spondylitis (AS) patients.

METHODS: This investigation was a 12-week randomized, placebo-controlled, phase I/II clinical trial involving 75 AS patients that were randomly divided into 3 groups: 25 as placebo, 25 Guluronic acid and 25 naproxen groups. Patients who had AS with active disease at baseline according to the modified New York criteria were considered for this trial. The primary consequence measure was the Appraisement of Spondyloarthritis International Society (ASAS) 20 response-rate at week 12.

RESULTS: There were no statistically significant differences between groups at the entry. ASAS20 response at week 12 was achieved (60.8%) in patients receiving Guluronic acid compared with – (68.4% of) – patients in the naproxen group (p > 0.05) and (21.0%) of patients in the placebo group. In comparison with the placebo group from the baseline to week 12, patients who received Guluronic acid and naproxen showed significantly greater improvement in all secondary endpoints. Moreover, Guluronic acid decreased some inflammatory parameters more dramatically than naproxen and placebo group. Patients in the naproxen group had more incidence of gastrointestinal and others adverse events in comparison with Guluronic acid and placebo groups.

CONCLUSION: The present research indicated that Guluronic acid and naproxen are similar in terms of efficacy. However, Guluronic acid had more notable safety characteristics identifying information than naproxen. Accordingly, it is proposed that Guluronic acid could be appropriate for management of AS. Clinical trial identifier; IRCT2016091813739N4.

PMID: 31003148 [PubMed – indexed for MEDLINE]

PMID:
PubMed:31003148

DATE FOUND:
11/21/19 06:38AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31003148?dopt=Abstract

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

https://www.biorxiv.org/content/10.1101/517813v1.full

“therapies targeting the gut microbiome may be effective in the prevention and/or treatment of ankylosing spondylitis”

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome
Mark Asquith, Peter R. Sternes, Mary-Ellen Costello, Lisa Karstens, Sarah Diamond, Tammy M. Martin, Timothy D. Spector, Kim-Anh le Cao, James T. Rosenbaum, Matthew A. Brown
doi: https://doi.org/10.1101/517813
Now published in Arthritis & Rheumatology doi: 10.1002/art.40917
AbstractFull TextInfo/HistoryMetrics Preview PDF
ABSTRACT
Objectives HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms to account for these genotype-disease associations are largely unknown. HLA-alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and faecal microbiome signatures. Whether these changes are cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examine the effect of HLA-B27 and HLA-DRB1 RA-risk alleles on the composition of the intestinal microbiome in healthy individuals.

Methods 568 samples from 6 intestinal sites were collected from 107 otherwise healthy unrelated subjects and stool samples from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S rRNA bacterial marker gene. All patients were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data.

Results Association was observed between HLA-B27 genotype, and RA-risk HLA-DRB1 alleles, and overall microbial composition (P=0.0002 and P=0.00001 respectively). These associations were replicated in the TwinsUK cohort stool samples (P=0.023 and P=0.033 respectively).

Conclusions This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA-B27 and –DRB1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome, and suggest that therapies targeting the microbiome may be effective in their prevention and/or treatment.

INTRODUCTION

Back to top