Pub Date : 2024-07-04DOI: 10.55563/clinexprheumatol/3mxsll
Ilaria Maccora, Valerio Accardo, Marco Cattalini, Ilaria Pagnini, Andrea Taddio, Edoardo Marrani, Francesco La Torre, Maria Vincenza Mastrolia, Irene Bellicini, Serena Pastore, Gabriele Simonini
Objectives: TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse.
Methods: In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi.
Results: 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoJIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent OligoJIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001).
Conclusions: Younger age at onset, uveitis, duration of tapering, and not-persistent OligoJIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.
{"title":"Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.","authors":"Ilaria Maccora, Valerio Accardo, Marco Cattalini, Ilaria Pagnini, Andrea Taddio, Edoardo Marrani, Francesco La Torre, Maria Vincenza Mastrolia, Irene Bellicini, Serena Pastore, Gabriele Simonini","doi":"10.55563/clinexprheumatol/3mxsll","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/3mxsll","url":null,"abstract":"<p><strong>Objectives: </strong>TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse.</p><p><strong>Methods: </strong>In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi.</p><p><strong>Results: </strong>136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoJIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent OligoJIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001).</p><p><strong>Conclusions: </strong>Younger age at onset, uveitis, duration of tapering, and not-persistent OligoJIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab.
Methods: We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpaşa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records.
Results: Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection.
Conclusions: Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.
{"title":"Tocilizumab may not be a good option for vascular involvement due to Behçet's syndrome.","authors":"Ayse Ozdede, Sinem Nihal Esatoglu, Emine Sebnem Durmaz, Alican Karakoc, Hande Ogun, Gulen Hatemi, Melike Melikoglu, Emire Seyahi","doi":"10.55563/clinexprheumatol/3myixe","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/3myixe","url":null,"abstract":"<p><strong>Objectives: </strong>Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab.</p><p><strong>Methods: </strong>We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpaşa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records.</p><p><strong>Results: </strong>Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection.</p><p><strong>Conclusions: </strong>Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-01DOI: 10.55563/clinexprheumatol/ua2zfc
Pierre-Yves Montagnon, Marine Beauger, Marion Couderc, Anne Tournadre, Martin Soubrier, Sylvain Mathieu
{"title":"Haptoglobin blood assay to assess treatment compliance in rheumatoid arthitis patients treated with tocilizumab.","authors":"Pierre-Yves Montagnon, Marine Beauger, Marion Couderc, Anne Tournadre, Martin Soubrier, Sylvain Mathieu","doi":"10.55563/clinexprheumatol/ua2zfc","DOIUrl":"10.55563/clinexprheumatol/ua2zfc","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: While multiple studies have investigated treatment persistence rates with intravenous abatacept, limited information is available about real-world treatment continuation with the subcutaneous form. The international ASCORE study described the characteristics and treatment persistence of real-world patients with rheumatoid arthritis (RA) receiving subcutaneous abatacept. This article presents the findings of the French cohort.
Methods: This was an observational study in French RA patients who initiated subcutaneous abatacept between August 2014 and January 2017. The primary endpoint was treatment maintenance at 2 years, analysed according to the number of previous biologic therapies.
Results: Of 546 evaluable patients, 281 (51.5%) were biologic-naive, 265 (48.5%) had experienced failure with 1 (n=134; 24.5%) or ≥2 (n=131; 24.0%) biologic therapies. At enrolment, patients who had experienced failure with ≥1 biologic therapy had more erosions and a longer duration of RA compared with biologic-naive patients, but had comparable mean disease activity scores. Overall, 43.0% of patients (95% confidence interval 38.6-47.2) were still taking subcutaneous abatacept at 2 years, which was comparable with that in other countries participating in ASCORE. The abatacept persistence rate was higher in biologic-naive patients (48.8%) than in those with 1 (40.9%) or ≥2 (32.8%) biologic therapy failures. The main reason for discontinuing abatacept was lack of efficacy (46.6%).
Conclusions: In current practice in France, the rate of subcutaneous abatacept persistence at 2 years was comparable with that of the intravenous form. Treatment persistence was higher when abatacept was used as first-line versus later-line biologic therapy.
{"title":"Two-year treatment persistence with subcutaneous abatacept in rheumatoid arthritis: results from the French cohort of the ASCORE study.","authors":"René-Marc Flipo, Arnaud Constantin, Philippe Goupille, Mélanie Chartier, Anaël Ohayon, Xavier Mariette","doi":"10.55563/clinexprheumatol/ddx0fz","DOIUrl":"10.55563/clinexprheumatol/ddx0fz","url":null,"abstract":"<p><strong>Objectives: </strong>While multiple studies have investigated treatment persistence rates with intravenous abatacept, limited information is available about real-world treatment continuation with the subcutaneous form. The international ASCORE study described the characteristics and treatment persistence of real-world patients with rheumatoid arthritis (RA) receiving subcutaneous abatacept. This article presents the findings of the French cohort.</p><p><strong>Methods: </strong>This was an observational study in French RA patients who initiated subcutaneous abatacept between August 2014 and January 2017. The primary endpoint was treatment maintenance at 2 years, analysed according to the number of previous biologic therapies.</p><p><strong>Results: </strong>Of 546 evaluable patients, 281 (51.5%) were biologic-naive, 265 (48.5%) had experienced failure with 1 (n=134; 24.5%) or ≥2 (n=131; 24.0%) biologic therapies. At enrolment, patients who had experienced failure with ≥1 biologic therapy had more erosions and a longer duration of RA compared with biologic-naive patients, but had comparable mean disease activity scores. Overall, 43.0% of patients (95% confidence interval 38.6-47.2) were still taking subcutaneous abatacept at 2 years, which was comparable with that in other countries participating in ASCORE. The abatacept persistence rate was higher in biologic-naive patients (48.8%) than in those with 1 (40.9%) or ≥2 (32.8%) biologic therapy failures. The main reason for discontinuing abatacept was lack of efficacy (46.6%).</p><p><strong>Conclusions: </strong>In current practice in France, the rate of subcutaneous abatacept persistence at 2 years was comparable with that of the intravenous form. Treatment persistence was higher when abatacept was used as first-line versus later-line biologic therapy.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The treatment options for rheumatoid arthritis (RA) have expanded with the availability of biological and targeted synthetic disease-modifying anti-rheumatic drugs. Despite all these developments and treatments, an important group of patients remain symptomatic and have not achieved clinical remission. The terminology "difficult-to-treat" (D2T) has been developed to describe this group. This study aimed to determine the frequency of D2T RA among our patients according to the EULAR 2021 definition of D2T RA and to identify the differences in demographic and disease characteristics, contributing factors, and disease burden.
Methods: The study included 302 consecutive patients diagnosed with RA according to the 2010 ACR criteria. These patients were categorised into the D2T and non-D2T RA groups. Risk factors independently associated with D2T RA were identified using logistic regression analysis.
Results: Of the 302 patients (mean age, 56.5 years, 80.1% female, 75% seropositive), 27 (8.9%) had D2T RA. Those with D2T RA had a lower age at diagnosis and longer disease duration and showed significantly higher rates of peripheral erosion, Sjögren's syndrome, extra-articular manifestations, and PtGA-PhGA discordance, together with high disease activity scores. Furthermore, the median number of comorbidities and concomitant fibromyalgia was significantly higher in the D2T RA group. In the multiple regression analysis, D2T RA was independently associated with higher HAQ-DI, RF levels, and concomitant fibromyalgia.
Conclusions: D2T RA requires more intensive management, and patients with D2T RA have higher disease activity, poorer functional status, and quality of life than those without D2T RA.
目的:随着生物和靶向合成改变病情抗风湿药物的出现,类风湿性关节炎(RA)的治疗方案也在不断扩大。尽管取得了所有这些进展和治疗方法,但仍有相当一部分患者症状不明显,临床症状未得到缓解。"难以治疗"(D2T)这一术语就是用来描述这部分患者的。本研究旨在根据 EULAR 2021 年对 D2T RA 的定义,确定我国患者中 D2T RA 的发生率,并识别人口统计学和疾病特征、诱因和疾病负担方面的差异:研究纳入了302名根据2010年ACR标准诊断为RA的连续患者。这些患者被分为D2T和非D2T RA两组。通过逻辑回归分析确定了与D2T RA独立相关的风险因素:在 302 名患者(平均年龄 56.5 岁,80.1% 为女性,75% 血清呈阳性)中,27 人(8.9%)患有 D2T RA。D2T型RA患者确诊年龄较低,病程较长,外周侵蚀、斯约格伦综合征、关节外表现、PtGA-PhGA不一致以及疾病活动度评分较高的比例明显较高。此外,D2T RA 组的合并症和纤维肌痛的中位数也明显较高。在多元回归分析中,D2T RA与较高的HAQ-DI、RF水平和并发纤维肌痛独立相关:结论:D2T RA 需要更深入的治疗,与没有 D2T RA 的患者相比,D2T RA 患者的疾病活动度更高,功能状态和生活质量更差。
{"title":"Challenges and insights in managing difficult-to-treat rheumatoid arthritis: real-world clinical perspectives.","authors":"Gülay Alp, Haluk Cinakli, İdil Kurut Aysin, Dilek Solmaz, Servet Akar","doi":"10.55563/clinexprheumatol/nyu9er","DOIUrl":"10.55563/clinexprheumatol/nyu9er","url":null,"abstract":"<p><strong>Objectives: </strong>The treatment options for rheumatoid arthritis (RA) have expanded with the availability of biological and targeted synthetic disease-modifying anti-rheumatic drugs. Despite all these developments and treatments, an important group of patients remain symptomatic and have not achieved clinical remission. The terminology \"difficult-to-treat\" (D2T) has been developed to describe this group. This study aimed to determine the frequency of D2T RA among our patients according to the EULAR 2021 definition of D2T RA and to identify the differences in demographic and disease characteristics, contributing factors, and disease burden.</p><p><strong>Methods: </strong>The study included 302 consecutive patients diagnosed with RA according to the 2010 ACR criteria. These patients were categorised into the D2T and non-D2T RA groups. Risk factors independently associated with D2T RA were identified using logistic regression analysis.</p><p><strong>Results: </strong>Of the 302 patients (mean age, 56.5 years, 80.1% female, 75% seropositive), 27 (8.9%) had D2T RA. Those with D2T RA had a lower age at diagnosis and longer disease duration and showed significantly higher rates of peripheral erosion, Sjögren's syndrome, extra-articular manifestations, and PtGA-PhGA discordance, together with high disease activity scores. Furthermore, the median number of comorbidities and concomitant fibromyalgia was significantly higher in the D2T RA group. In the multiple regression analysis, D2T RA was independently associated with higher HAQ-DI, RF levels, and concomitant fibromyalgia.</p><p><strong>Conclusions: </strong>D2T RA requires more intensive management, and patients with D2T RA have higher disease activity, poorer functional status, and quality of life than those without D2T RA.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-03-03DOI: 10.55563/clinexprheumatol/7pcgv7
Yali Wu, Xin Li, Jing Ke, Baoyu Zhang, Dong Zhao
Objectives: The aberrant expression of omentin-1 had been reported in type 2 diabetes and cardiovascular disease. Here, we investigated the expression and role of omentin-1 in rheumatoid arthritis (RA).
Methods: The expression of omentin-1 in RA and in the normal population was detected by ELISA and immunohistochemistry, and collagen-induced arthritis (CIA) mice were used to detect the role of omentin-1 in RA.
Results: We found that the expression of omentin-1 was elevated in serum of RA patients compared with healthy controls (p=0.004), and in the RA disease activity group compared with the disease remission group (p<0.001). In addition, the level of omentin-1 in RA patients was positively correlated with CRP (r=0.427, p=0.002), ESR (r=0.454, p<0.001) and DAS28 (r=0.496, p<0.001; r=0.661, p<0.001, respectively). Multivariable analysis showed that omentin-1 alone was associated with disease activity state (OR=1.018, p=0.004). Immunohistochemical results showed that omentin-1 was increased in the synovium of RA and CIA mice. Omentin-1 injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia and bone erosion in CIA mice. Moreover, omentin-1 treatment markedly enhanced IL-6, TNF-α, MMP-3, MMP-13 and RANKL in the joint tissue of CIA mice.
Conclusions: Our results suggested that omentin-1 was up-regulated in RA and can exacerbate synovitis and joint destruction which may provide new insight into the pathogenesis of RA.
研究目的网蛋白-1在2型糖尿病和心血管疾病中的异常表达已有报道。在此,我们研究了类风湿性关节炎(RA)中网织蛋白-1的表达和作用:方法:通过 ELISA 和免疫组化检测网织蛋白-1 在 RA 和正常人群中的表达,并利用胶原诱导的关节炎(CIA)小鼠检测网织蛋白-1 在 RA 中的作用:结果:我们发现,与健康对照组相比,网织蛋白-1在RA患者血清中的表达升高(p=0.004);与疾病缓解组相比,网织蛋白-1在RA疾病活动组中的表达升高(pConclusions):我们的研究结果表明,网织蛋白-1在RA中上调,并可加重滑膜炎和关节破坏,这可能为了解RA的发病机制提供了新的视角。
{"title":"Increased expression of omentin-1 is associated with synovitis and bone destruction in rheumatoid arthritis.","authors":"Yali Wu, Xin Li, Jing Ke, Baoyu Zhang, Dong Zhao","doi":"10.55563/clinexprheumatol/7pcgv7","DOIUrl":"10.55563/clinexprheumatol/7pcgv7","url":null,"abstract":"<p><strong>Objectives: </strong>The aberrant expression of omentin-1 had been reported in type 2 diabetes and cardiovascular disease. Here, we investigated the expression and role of omentin-1 in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>The expression of omentin-1 in RA and in the normal population was detected by ELISA and immunohistochemistry, and collagen-induced arthritis (CIA) mice were used to detect the role of omentin-1 in RA.</p><p><strong>Results: </strong>We found that the expression of omentin-1 was elevated in serum of RA patients compared with healthy controls (p=0.004), and in the RA disease activity group compared with the disease remission group (p<0.001). In addition, the level of omentin-1 in RA patients was positively correlated with CRP (r=0.427, p=0.002), ESR (r=0.454, p<0.001) and DAS28 (r=0.496, p<0.001; r=0.661, p<0.001, respectively). Multivariable analysis showed that omentin-1 alone was associated with disease activity state (OR=1.018, p=0.004). Immunohistochemical results showed that omentin-1 was increased in the synovium of RA and CIA mice. Omentin-1 injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia and bone erosion in CIA mice. Moreover, omentin-1 treatment markedly enhanced IL-6, TNF-α, MMP-3, MMP-13 and RANKL in the joint tissue of CIA mice.</p><p><strong>Conclusions: </strong>Our results suggested that omentin-1 was up-regulated in RA and can exacerbate synovitis and joint destruction which may provide new insight into the pathogenesis of RA.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway.
Methods: The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats.
Results: Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats.
Conclusions: The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.
{"title":"Exploring the supplementary potential of all-trans retinoic acid with methotrexate in rheumatoid arthritis: modulation of synovial cell apoptosis and autophagy.","authors":"Yiqi Zhang, Jiangchun Shi, Yumeng Xie, Huangfang Shao, Yanhua Ning, Yun Li","doi":"10.55563/clinexprheumatol/3pd9rp","DOIUrl":"10.55563/clinexprheumatol/3pd9rp","url":null,"abstract":"<p><strong>Objectives: </strong>The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway.</p><p><strong>Methods: </strong>The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats.</p><p><strong>Results: </strong>Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats.</p><p><strong>Conclusions: </strong>The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-02-20DOI: 10.55563/clinexprheumatol/99pc16
Zhaojuan Shi, Zhe Yang, Datian Su, Juan Cheng, Zhaoxia Shi, Mei Wang, Hui Zheng, Jiankui Han, Changqin Li, Jian Qin
Objectives: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS.
Methods: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators.
Results: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05).
Conclusions: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.
{"title":"Prediction of the activity of early ankylosing spondylitis using radiomics texture analysis on short tau inversion recovery (STIR).","authors":"Zhaojuan Shi, Zhe Yang, Datian Su, Juan Cheng, Zhaoxia Shi, Mei Wang, Hui Zheng, Jiankui Han, Changqin Li, Jian Qin","doi":"10.55563/clinexprheumatol/99pc16","DOIUrl":"10.55563/clinexprheumatol/99pc16","url":null,"abstract":"<p><strong>Objectives: </strong>The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS.</p><p><strong>Methods: </strong>43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators.</p><p><strong>Results: </strong>In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05).</p><p><strong>Conclusions: </strong>Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-01DOI: 10.55563/clinexprheumatol/qldfoi
Haluk Cinakli, Gülay Alp
{"title":"Gender disparity among the academics of rheumatology in Turkey.","authors":"Haluk Cinakli, Gülay Alp","doi":"10.55563/clinexprheumatol/qldfoi","DOIUrl":"10.55563/clinexprheumatol/qldfoi","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-07-18DOI: 10.55563/clinexprheumatol/7f52vl
Giammarco De Mattia, Michele Maffi, Maurizio Mazzantini
Osteoporosis is a skeletal disease characterised by reduced bone mass and deterioration of bone microarchitecture, underlying a higher risk of fragility fractures. Several options are available for its treatment, including both anti-resorptive and anabolic agents. The present review discusses and summarises the most recent literature on anabolic treatment, with a focus on abaloparatide, and on the assessment of fragility fracture risk, with a focus on trabecular bone score. Finally, we provide a discussion on the effects of different antiosteoporotic medications in terms of fragility fracture risk reduction.
{"title":"Anabolic treatment for osteoporosis and fragility fracture risk: one year in review 2024.","authors":"Giammarco De Mattia, Michele Maffi, Maurizio Mazzantini","doi":"10.55563/clinexprheumatol/7f52vl","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/7f52vl","url":null,"abstract":"<p><p>Osteoporosis is a skeletal disease characterised by reduced bone mass and deterioration of bone microarchitecture, underlying a higher risk of fragility fractures. Several options are available for its treatment, including both anti-resorptive and anabolic agents. The present review discusses and summarises the most recent literature on anabolic treatment, with a focus on abaloparatide, and on the assessment of fragility fracture risk, with a focus on trabecular bone score. Finally, we provide a discussion on the effects of different antiosteoporotic medications in terms of fragility fracture risk reduction.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}