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1.
The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.
Bertoldo, E, Adami, G, Rossini, M, Giollo, A, Orsolini, G, Viapiana, O, Gatti, D, Fassio, A
Frontiers in endocrinology. 2021;:620920
Abstract
The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.
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2.
The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial.
Ahmadi, M, Hajialilo, M, Dolati, S, Eghbal-Fard, S, Heydarlou, H, Ghaebi, M, Ghassembaglou, A, Aghebati-Maleki, L, Samadi Kafil, H, Kamrani, A, et al
Journal of cellular biochemistry. 2020;(1):103-110
Abstract
AIM: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. METHODS Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-β, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines. RESULTS After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-β and low levels of IL-6 production than control group. CONCLUSION The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.
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3.
[Huangqin Qingre Chubi Capsules in improving oxidative stress of patients with ankylosing spondylitis via activating PPARγ mediated AMPK/FOXO3a pathway].
Huang, D, Liu, J, Zong, RK, Wan, L
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2020;(2):451-456
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.
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4.
Evaluation of the impact of a nurse-led program of systematic screening of comorbidities in patients with axial spondyloarthritis: The results of the COMEDSPA prospective, controlled, one year randomized trial.
Molto, A, Gossec, L, Poiraudeau, S, Claudepierre, P, Soubrier, M, Fayet, F, Wendling, D, Gaudin, P, Dernis, E, Guis, S, et al
Seminars in arthritis and rheumatism. 2020;(4):701-708
Abstract
OBJECTIVE To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities. METHODS Prospective, randomized, controlled, open, 12-month trial (NCT02374749). PARTICIPANTS consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist) THE PROGRAM A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit. TREATMENT ALLOCATION random allocation (i.e. either this program or an educational program not presented here and considered here as the control group). MAIN OUTCOME change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management). RESULTS 502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p<0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p<0.01). CONCLUSIONS AND RELEVANCE This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.
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5.
Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial.
van der Heijde, D, Baraliakos, X, Gensler, LS, Maksymowych, WP, Tseluyko, V, Nadashkevich, O, Abi-Saab, W, Tasset, C, Meuleners, L, Besuyen, R, et al
Lancet (London, England). 2018;(10162):2378-2387
Abstract
BACKGROUND At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. METHODS In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270. FINDINGS Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was -1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, with a least squares mean difference between groups of -0·85 (95% CI -1·17 to -0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients in each group, the most common being nasopharyngitis (in two patients in the filgotinib group and in four patients in the placebo group). Treatment-emergent adverse events led to permanent treatment discontinuation in two patients (a case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in the placebo group). No deaths were reported during the study. INTERPRETATION Filgotinib is efficacious and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs. Further investigation of filgotinib for ankylosing spondylitis is warranted. FUNDING Galapagos and Gilead Sciences.
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6.
Gender Is a Risk Factor for Annual Decline in Estimated Glomerular Filtration Rate in Patients Treated with Biological DMARDs in Rheumatoid Arthritis and Ankylosing Spondylitis: a Retrospective Observational Study.
Kim, SK, Choe, JY
Journal of Korean medical science. 2018;(30):e188
Abstract
BACKGROUND This study identified the risk factors of changes in renal function in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) treated with biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS We retrospectively enrolled patients with RA (n = 293) and AS (n = 125) treated with bDMARDs. The estimated glomerular filter rate (eGFR) using the Modification of Diet in Renal Disease equation was applied for assessment of annual changes in renal function between initiation and last visit after bDMARD therapy. The annual change in eGFR was used as an indicator for change in renal function. Statistical significance was assessed by Mann-Whitney test, Spearman's correlation coefficient, and multivariate linear regression analysis. RESULTS The positive annual change in eGFR in women was significantly noted, compared to that in men (P = 0.004). The annual change in eGFR was different between men and women (P = 0.038) in RA, but not in AS patients (P = 0.126). In multivariate linear regression analysis, women patients and increased serum creatinine at baseline were closely associated with positive annual change in eGFR in both RA and AS patients. In RA patients, younger age and lower ESR level were considered risk factors of positive annual change in eGFR (P = 0.013 and P = 0.022, respectively). However, disease duration and duration of bDMARD use were not associated with annual change in eGFR. CONCLUSION This study found that gender, especially men, might be responsible for annual decline in eGFR in RA and AS patients treated with bDMARDs.
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7.
Joint involvement in Mexican patients with ulcerative colitis: a hospital-based retrospective study.
Yamamoto-Furusho, JK, Sarmiento-Aguilar, A
Clinical rheumatology. 2018;(3):677-682
Abstract
The most frequent extra-intestinal manifestation in ulcerative colitis (UC) around the world is joint involvement. There are no previous data in Latin America that is about this aspect of disease; hence, the aim of this study was to determine the frequency and factors associated to joint involvement in Mexican patients with UC. A total of 295 patients with histological diagnosis of UC were studied, divided into two groups: (1) 154 cases with at least one joint affection (arthralgia, peripheral, or axial arthropathy (sacroilitis (SI) or ankylosing spondylitis (AS))) and (2) 141 controls that had never presented any joint involvement during the clinical course of UC. Demographic, clinical, and laboratory variables were collected from the clinical records, at the time of presentation of the joint involvement for the cases and with the last information available for controls. A total of 52.2% of the patients had joint involvement, which was also the most frequent extra-intestinal manifestation (EIM). The frequency of peripheral arthralgia was 46.8% and of axial arthropathy was 5.4% (2.7% AS, 2.4% SI, and 0.3% both). The female gender (P = 0.01, OR = 3.061 95% CI: 1.311-7.15), elevated erythrocyte sedimentation rate (ESR) (P = 0.07, OR = 8.04 95% CI: 1.759-36.764), and moderate disease activity by Truelove and Witts criteria (P = 0.024, OR = 4.37 95% CI: 1.211-15.78) were factors associated at the time of presentation of the joint affection. Joint involvement is the most frequent EIM in Mexican patients with UC. The female gender, elevated ESR, and disease activity are factors associated with its presentation.
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8.
A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis.
Klingberg, E, Strid, H, Ståhl, A, Deminger, A, Carlsten, H, Öhman, L, Forsblad-d'Elia, H
Arthritis research & therapy. 2017;(1):21
Abstract
BACKGROUND Patients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD. METHODS Fecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period. RESULTS Fecal calprotectin >50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by <200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin. CONCLUSIONS Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00858819 . Registered 9 March 2009. Last updated 28 May 2015.
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9.
Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.
Rollefstad, S, Ikdahl, E, Hisdal, J, Olsen, IC, Holme, I, Hammer, HB, Smerud, KT, Kitas, GD, Pedersen, TR, Kvien, TK, et al
Arthritis & rheumatology (Hoboken, N.J.). 2015;(7):1718-28
Abstract
OBJECTIVE Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. METHODS Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. RESULTS The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. CONCLUSION Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.
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10.
[Core set of behavioral recommendations for patients with ankylosing spondylitis].
Feldtkeller, E, Lind-Albrecht, G, Rudwaleit, M
Zeitschrift fur Rheumatologie. 2013;(10):993-6
Abstract
OBJECTIVES Patients with ankylosing spondylitis (AS) can contribute to a favorable disease course by their own behaviour and environmental adaptations. However, no standardized consensus recommendations on patient behavior and adaptations exist, neither internationally nor nationally. The aim of this study was to establish a core set of recommendations concerning favorable patient behavior to be given to patients with AS by rheumatologists. METHODS An extended literature research in the scientific and patient-oriented literature revealed 70 recommendations. These recommendations were evaluated and ranked by importance at a meeting of the Ankylosing Spondylitis International Federation (ASIF, 26 participants from 13 countries) in November 2011. The remaining 59 recommendations were extensively discussed, supplemented, partially reworded, condensed and those with the highest priority were selected by consensus at a seminar of local branch leaders of the AS patient organization in Germany (Deutsche Vereinigung Morbus Bechterew) in March 2012 (80 participants, 95% patients with AS). RESULTS The core set encompasses 1) a general statement on living with AS and 2) recommendations in the areas of sitting position, walking, sleeping, at work, exercising, sports and recreational activities, diet and life style, sexuality and pregnancy, fall prevention, car driving and membership in an AS-specific patient organization. The selected recommendations received agreement by 80-100% of the patients. Some recommendations (e.g. fall prevention and car driving) are more relevant to patients with advanced and usually longstanding disease, i.e. with advanced ankylosis or osteoporosis. CONCLUSIONS For the first time a core set of recommendations for the behavior of patients with AS was created in collaboration with many persons affected by the disease. Patients with AS should receive these recommendations from their rheumatologists, ideally early in the disease course. The German version of this core set is presented in this article.