{"title":"Outcome measure in childhood Sjögren's disease: where do we stand?","authors":"Edoardo Marrani, Valerio Maniscalco, Chiara Baldini, Gabriele Simonini","doi":"10.55563/clinexprheumatol/faykmn","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/faykmn","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125000","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}
{"title":"Clinical spectrum of small-vessel vasculitis related to cocaine consumption: data from an Italian cohort.","authors":"Silvia Grazzini, Edoardo Conticini, Alessia Giorli, Stefano Gentileschi, Luca Cantarini, Bruno Frediani","doi":"10.55563/clinexprheumatol/z41j3b","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/z41j3b","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124998","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 : 2024-08-30DOI: 10.55563/clinexprheumatol/6lcful
Fernando Rengifo-García, Elena Heras-Recuero, Teresa Blázquez-Sánchez, Claritza Caraballo-Salazar, Arantxa Torres-Roselló, Miguel Ángel González-Gay
{"title":"Biopsy-proven giant cell arteritis in a patient with ankylosing spondylitis: a rare coincidence of two diseases at different stages of life.","authors":"Fernando Rengifo-García, Elena Heras-Recuero, Teresa Blázquez-Sánchez, Claritza Caraballo-Salazar, Arantxa Torres-Roselló, Miguel Ángel González-Gay","doi":"10.55563/clinexprheumatol/6lcful","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/6lcful","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104893","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: To develop an easy-to-use and efficient clinical score to identify monogenic lupus based on clinical presentations and to stratify patients who may benefit from confirmatory molecular genetic testing.
Methods: A comprehensive literature review identified 55 distinct items across 12 clinical and laboratory domains, narrowed down to the top ten by a panel of 12 expert paediatric rheumatologists with 80% consensus. The proposed score was tested in a pilot study on 10 patients with monogenic lupus and 30 control subjects with various autoimmune and autoinflammatory diseases. All patients, both with monogenic lupus and the control group, were then scored, and a receiver operating characteristic curve was employed to determine the threshold that distinguishes monogenic lupus from non-monogenic lupus.
Results: The clinical score comprised 10 items. Among all patients, the most frequent items were antinuclear antibody positivity and consanguinity, followed by early disease onset (<5 years), with no significant differences between monogenic lupus patients and the controls. However, the monogenic lupus patients exhibited significantly higher rates of family history of lupus, failure to thrive, cutaneous lesions, brain imaging changes, a low C1q level, and recurrent infections. Also, they achieved the highest scores compared to the controls. A score of more than three was found to be highly predictive for diagnosing monogenic lupus, with a sensitivity of 90% and a specificity of 90%.
Conclusions: Our clinical score appears to be a valuable tool for the early identification of patients with monogenic lupus who may require further molecular genetic testing for confirmation.
{"title":"A proposed clinical tool to identify high-risk patients for monogenic lupus: a pilot study.","authors":"Sulaiman M Al-Mayouf, Djohra Hadef, Najla Aljaberi, Nasim Movahedi, Ashwaq AlEed, Abdulaziz Almutairi, Abdulrahman Asiri, Stefano Volpi, Marco Gattorno, Chao-Yi Wu, Hani Tamim, Alhanouf Al-Saleem","doi":"10.55563/clinexprheumatol/tjt58t","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/tjt58t","url":null,"abstract":"<p><strong>Objectives: </strong>To develop an easy-to-use and efficient clinical score to identify monogenic lupus based on clinical presentations and to stratify patients who may benefit from confirmatory molecular genetic testing.</p><p><strong>Methods: </strong>A comprehensive literature review identified 55 distinct items across 12 clinical and laboratory domains, narrowed down to the top ten by a panel of 12 expert paediatric rheumatologists with 80% consensus. The proposed score was tested in a pilot study on 10 patients with monogenic lupus and 30 control subjects with various autoimmune and autoinflammatory diseases. All patients, both with monogenic lupus and the control group, were then scored, and a receiver operating characteristic curve was employed to determine the threshold that distinguishes monogenic lupus from non-monogenic lupus.</p><p><strong>Results: </strong>The clinical score comprised 10 items. Among all patients, the most frequent items were antinuclear antibody positivity and consanguinity, followed by early disease onset (<5 years), with no significant differences between monogenic lupus patients and the controls. However, the monogenic lupus patients exhibited significantly higher rates of family history of lupus, failure to thrive, cutaneous lesions, brain imaging changes, a low C1q level, and recurrent infections. Also, they achieved the highest scores compared to the controls. A score of more than three was found to be highly predictive for diagnosing monogenic lupus, with a sensitivity of 90% and a specificity of 90%.</p><p><strong>Conclusions: </strong>Our clinical score appears to be a valuable tool for the early identification of patients with monogenic lupus who may require further molecular genetic testing for confirmation.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104892","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 : 2024-08-27DOI: 10.55563/clinexprheumatol/r35akp
Stefano Lanni, Orazio De Lucia, Dario Consonni, Federica Chironi, Stefania Costi, Silvia Maria Orsi, Gisella Beretta, Martina Rossano, Roberto Caporali, Carlo Agostoni, Giovanni Filocamo
Objectives: To determine features and frequency of ultrasound (US)-detected tenosynovitis in ankles with clinically active disease and to investigate whether its detection may affect the achievement of inactive disease in patients with new-onset juvenile idiopathic arthritis (JIA).
Methods: The study included children with new-onset JIA and clinically active disease of the ankle. Based on US, patients were stratified as having isolated arthritis or as having tenosynovitis irrespective of the presence of concomitant arthritis in the ankle. Estimation of patients who were able to achieve clinically inactive disease 6 months after starting treatment was assessed by the Kaplan-Meier method. Cox model was used to calculate hazard ratio (HR) and 95% confidence interval (CI). Reliability of US was tested using kappa statistic.
Results: Forty-five patients were recruited. On US, tenosynovitis of the ankle was detected in 28 patients (62.2%); isolated arthritis was found in 17 patients (37.8%). The medial and lateral tendon compartments were the tendon sites most frequently inflamed. Patients with tenosynovitis had similar likelihood of those without tenosynovitis to achieve clinically inactive disease (60.7% and 58.8%, respectively; HR 1.12, 95%CI:0.51-2.45). In the subanalysis excluding patients who were given biologics, the probability of experiencing inactive disease was slightly higher for patients with tenosynovitis compared to those without (64.7% and 54.5%, respectively; HR 1.56, 95%CI: 0.58-4.24). The rate of US reliability was high.
Conclusions: US-detected tenosynovitis is frequent in ankles with clinical arthritis at JIA onset but does not impair the chance of achieving clinically inactive disease in the early disease phase.
{"title":"Ultrasound-detected tenosynovitis in ankles with clinical arthritis and short-term outcome of patients with new-onset juvenile idiopathic arthritis.","authors":"Stefano Lanni, Orazio De Lucia, Dario Consonni, Federica Chironi, Stefania Costi, Silvia Maria Orsi, Gisella Beretta, Martina Rossano, Roberto Caporali, Carlo Agostoni, Giovanni Filocamo","doi":"10.55563/clinexprheumatol/r35akp","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/r35akp","url":null,"abstract":"<p><strong>Objectives: </strong>To determine features and frequency of ultrasound (US)-detected tenosynovitis in ankles with clinically active disease and to investigate whether its detection may affect the achievement of inactive disease in patients with new-onset juvenile idiopathic arthritis (JIA).</p><p><strong>Methods: </strong>The study included children with new-onset JIA and clinically active disease of the ankle. Based on US, patients were stratified as having isolated arthritis or as having tenosynovitis irrespective of the presence of concomitant arthritis in the ankle. Estimation of patients who were able to achieve clinically inactive disease 6 months after starting treatment was assessed by the Kaplan-Meier method. Cox model was used to calculate hazard ratio (HR) and 95% confidence interval (CI). Reliability of US was tested using kappa statistic.</p><p><strong>Results: </strong>Forty-five patients were recruited. On US, tenosynovitis of the ankle was detected in 28 patients (62.2%); isolated arthritis was found in 17 patients (37.8%). The medial and lateral tendon compartments were the tendon sites most frequently inflamed. Patients with tenosynovitis had similar likelihood of those without tenosynovitis to achieve clinically inactive disease (60.7% and 58.8%, respectively; HR 1.12, 95%CI:0.51-2.45). In the subanalysis excluding patients who were given biologics, the probability of experiencing inactive disease was slightly higher for patients with tenosynovitis compared to those without (64.7% and 54.5%, respectively; HR 1.56, 95%CI: 0.58-4.24). The rate of US reliability was high.</p><p><strong>Conclusions: </strong>US-detected tenosynovitis is frequent in ankles with clinical arthritis at JIA onset but does not impair the chance of achieving clinically inactive disease in the early disease phase.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104906","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 : 2024-08-27DOI: 10.55563/clinexprheumatol/a51j2e
Roberto Troiani, Saverio La Bella, Mario Muselli, Maurizia D'Egidio, Giulia Sassano, Armando Di Ludovico, Giulia Di Donato, Federico Lauriola, Emma Altobelli, Francesco Chiarelli, Luciana Breda
Objectives: An important area of research in juvenile idiopathic arthritis (JIA) aims to identify sensitive and reliable biomarkers of disease activity. The key iron-regulatory hormone hepcidin-25 (HEP) has been advocated as a potential biomarker to assess anaemia of chronic disease and iron deficiency in adults with rheumatoid arthritis.
Methods: We performed a cross-sectional study evaluating the utility of serum HEP in 79 non-systemic onset JIA patients (14 males, 65 females), with/without anaemia, determining its correlations with disease activity, assessed by the JIA Disease Activity Score (JADAS)-27, anaemia parameters, and iron status indices.
Results: Significant positive correlations for serum HEP levels were found with the JADAS-27 score (r=0.8988, p<0.0001), and significant differences were found in HEP serum levels between active and inactive patients (8.6 IQR 10.0 ng/mL vs. 2.9 IQR 1.9 ng/mL; p<0.0001). Mean serum HEP concentrations were significantly greater in high disease activity group than in others (p<0.0001). At the ROC curve, an HEP level >4.35 ng/mL discriminated subjects with active disease with a sensitivity of 91.8% and a specificity of 80.0% (AUC: 0.93; 95% CI: 0.88-0.98). Moreover, HEP levels were significantly higher in anaemic, iron repleted and active disease patients.
Conclusions: HEP is associated with JIA disease activity, and it could be useful in early detection and monitoring of disease exacerbations. These findings highlight that inflammation plays a major role in HEP induction and point out that HEP could be directly implicated in the JIA inflammatory cascade.
研究目的:幼年特发性关节炎(JIA)研究的一个重要领域是确定敏感可靠的疾病活动生物标志物。关键的铁调节激素血钙素-25(HEP)被认为是一种潜在的生物标志物,可用于评估慢性病贫血和类风湿关节炎成人患者的铁缺乏症:我们进行了一项横断面研究,评估了血清 HEP 在 79 名非系统性发病 JIA 患者(14 名男性,65 名女性)中的效用,这些患者伴有/不伴有贫血,并确定了血清 HEP 与 JIA 疾病活动性评分 (JADAS)-27 评估的疾病活动性、贫血参数和铁状态指数之间的相关性:结果:血清 HEP 水平与 JADAS-27 评分呈显著正相关(r=0.8988,p4.35 ng/mL),对疾病活动性受试者的判别灵敏度为 91.8%,特异性为 80.0%(AUC:0.93;95% CI:0.88-0.98)。此外,贫血、缺铁和活动性疾病患者的 HEP 水平明显更高:结论:HEP与JIA疾病的活动性有关,可用于疾病恶化的早期检测和监测。这些发现强调了炎症在 HEP 诱导过程中的重要作用,并指出 HEP 可能直接参与了 JIA 的炎症级联反应。
{"title":"Serum hepcidin evaluation as a promising biomarker in juvenile idiopathic arthritis.","authors":"Roberto Troiani, Saverio La Bella, Mario Muselli, Maurizia D'Egidio, Giulia Sassano, Armando Di Ludovico, Giulia Di Donato, Federico Lauriola, Emma Altobelli, Francesco Chiarelli, Luciana Breda","doi":"10.55563/clinexprheumatol/a51j2e","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/a51j2e","url":null,"abstract":"<p><strong>Objectives: </strong>An important area of research in juvenile idiopathic arthritis (JIA) aims to identify sensitive and reliable biomarkers of disease activity. The key iron-regulatory hormone hepcidin-25 (HEP) has been advocated as a potential biomarker to assess anaemia of chronic disease and iron deficiency in adults with rheumatoid arthritis.</p><p><strong>Methods: </strong>We performed a cross-sectional study evaluating the utility of serum HEP in 79 non-systemic onset JIA patients (14 males, 65 females), with/without anaemia, determining its correlations with disease activity, assessed by the JIA Disease Activity Score (JADAS)-27, anaemia parameters, and iron status indices.</p><p><strong>Results: </strong>Significant positive correlations for serum HEP levels were found with the JADAS-27 score (r=0.8988, p<0.0001), and significant differences were found in HEP serum levels between active and inactive patients (8.6 IQR 10.0 ng/mL vs. 2.9 IQR 1.9 ng/mL; p<0.0001). Mean serum HEP concentrations were significantly greater in high disease activity group than in others (p<0.0001). At the ROC curve, an HEP level >4.35 ng/mL discriminated subjects with active disease with a sensitivity of 91.8% and a specificity of 80.0% (AUC: 0.93; 95% CI: 0.88-0.98). Moreover, HEP levels were significantly higher in anaemic, iron repleted and active disease patients.</p><p><strong>Conclusions: </strong>HEP is associated with JIA disease activity, and it could be useful in early detection and monitoring of disease exacerbations. These findings highlight that inflammation plays a major role in HEP induction and point out that HEP could be directly implicated in the JIA inflammatory cascade.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104903","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 : 2024-08-27DOI: 10.55563/clinexprheumatol/s12eoy
Maurizio Cutolo, Elvis Hysa, Nathalie Berghen, Tessa du Four, Andrea Cere, Kaat Wyckstandt, Emanuele Gotelli, Vanessa Smith
Objectives: Body mapping of normal values of skin thickness and hardness may be a useful aid in daily practice. By employing non-invasive techniques, our pilot study provides these values in healthy individuals using high frequency ultrasound (HFUS) and durometry in areas used to evaluate the modified Rodnan skin score (mRSS).
Methods: One-hundred-fifty-two healthy volunteers from Ghent and Genova University Hospitals (mean ages 31.2, 35.5, and 64.9 years), were evaluated to exclude rheumatologic diseases. HFUS and durometry were used to assess the dermal status in mRSS areas. Exploratory analyses were performed to assess the impact of demographic and anthropometric characteristics on intra-subject skin measurements. Statistical analysis was performed with Datatab®.
Results: The upper and lower arms exhibited significantly higher durometry values and lower dermal thickness compared to the trunk regions, underscoring distinct variations across these areas (all p<0.05). The hardest skin was found on the finger, while the thickest dermal measurements were at the abdomen and thighs. Dermal thickness was higher in men in multiple areas in the three cohorts, albeit with relatively modest effect sizes (r coefficients ranging between 0.02 and 0.6). Despite the presence of significant inter-group differences in dermal thickness, HFUS mapping showed similar topographical distributions in both centres.
Conclusions: Our study offers a comprehensive skin mapping status in healthy individuals. Key findings indicate lower dermal thickness in the upper arms, legs, and feet, and higher skin hardness in peripheral areas like fingers, compared to truncal regions.This skin mapping pilot study might provide the normal distribution values in outpatient clinics for physicians to be used when comparing the same areas in pathological conditions like systemic sclerosis-related fibrotic skin.
{"title":"Mapping in healthy subjects different body areas for dermal thickness and skin hardness by high frequency ultrasound and durometry.","authors":"Maurizio Cutolo, Elvis Hysa, Nathalie Berghen, Tessa du Four, Andrea Cere, Kaat Wyckstandt, Emanuele Gotelli, Vanessa Smith","doi":"10.55563/clinexprheumatol/s12eoy","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/s12eoy","url":null,"abstract":"<p><strong>Objectives: </strong>Body mapping of normal values of skin thickness and hardness may be a useful aid in daily practice. By employing non-invasive techniques, our pilot study provides these values in healthy individuals using high frequency ultrasound (HFUS) and durometry in areas used to evaluate the modified Rodnan skin score (mRSS).</p><p><strong>Methods: </strong>One-hundred-fifty-two healthy volunteers from Ghent and Genova University Hospitals (mean ages 31.2, 35.5, and 64.9 years), were evaluated to exclude rheumatologic diseases. HFUS and durometry were used to assess the dermal status in mRSS areas. Exploratory analyses were performed to assess the impact of demographic and anthropometric characteristics on intra-subject skin measurements. Statistical analysis was performed with Datatab®.</p><p><strong>Results: </strong>The upper and lower arms exhibited significantly higher durometry values and lower dermal thickness compared to the trunk regions, underscoring distinct variations across these areas (all p<0.05). The hardest skin was found on the finger, while the thickest dermal measurements were at the abdomen and thighs. Dermal thickness was higher in men in multiple areas in the three cohorts, albeit with relatively modest effect sizes (r coefficients ranging between 0.02 and 0.6). Despite the presence of significant inter-group differences in dermal thickness, HFUS mapping showed similar topographical distributions in both centres.</p><p><strong>Conclusions: </strong>Our study offers a comprehensive skin mapping status in healthy individuals. Key findings indicate lower dermal thickness in the upper arms, legs, and feet, and higher skin hardness in peripheral areas like fingers, compared to truncal regions.This skin mapping pilot study might provide the normal distribution values in outpatient clinics for physicians to be used when comparing the same areas in pathological conditions like systemic sclerosis-related fibrotic skin.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104896","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 : 2024-08-20DOI: 10.55563/clinexprheumatol/yg6rck
Flavia V Castelino, Ayodeji Adegunsoye
Patients with autoimmune disease-related interstitial lung disease may develop pulmonary fibrosis, which may become progressive. Progressive pulmonary fibrosis (PPF) is associated with poor outcomes. Antifibrotic therapies have shown efficacy as treatments for PPF in patients with autoimmune diseases, but new treatments are needed to slow or halt disease progression. Phosphodiesterases (PDEs) are enzymes that mediate the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Pre-clinical data suggest that preferential inhibition of PDE4B has the potential to slow the progression of pulmonary fibrosis by inhibiting inflammatory and fibrotic pathways, with a lower risk of gastrointestinal adverse events than associated with pan-PDE4 inhibitors. Nerandomilast (BI 1015550) is a preferential PDE4 inhibitor that has demonstrated anti-inflammatory and antifibrotic effects in pre-clinical studies. In a phase II trial in patients with idiopathic pulmonary fibrosis, nerandomilast (given alone or on top of background antifibrotic therapy) prevented a decrease in lung function over 12 weeks with an acceptable safety and tolerability profile. The phase III FIBRONEER-ILD trial is evaluating the efficacy and safety of nerandomilast, given alone or on top of nintedanib, in patients with PPF, including PPF associated with autoimmune diseases. In this article, we review the potential of PDE4B inhibition in the treatment of ILD associated with autoimmune diseases, including the pre-clinical and early clinical data available to date.
与自身免疫性疾病相关的间质性肺病患者可能会出现肺纤维化,并有可能发展为进行性肺纤维化。进行性肺纤维化(PPF)与不良预后有关。抗纤维化疗法已显示出治疗自身免疫性疾病患者肺纤维化的疗效,但仍需要新的疗法来减缓或阻止疾病的进展。磷酸二酯酶(PDE)是一种介导环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)水解的酶。临床前数据表明,优先抑制 PDE4B 有可能通过抑制炎症和纤维化途径来减缓肺纤维化的进展,而且与泛 PDE4 抑制剂相比,发生胃肠道不良反应的风险更低。Nerandomilast(BI 1015550)是一种优先PDE4抑制剂,在临床前研究中已显示出抗炎和抗纤维化作用。在一项针对特发性肺纤维化患者的 II 期试验中,nerandomilast(单独使用或在背景抗纤维化治疗的基础上使用)可在 12 周内防止肺功能下降,且安全性和耐受性均可接受。FIBRONEER-ILDⅢ期试验正在评估奈罗多米拉斯特单独或在宁替尼基础上用于肺纤维化(包括与自身免疫性疾病相关的肺纤维化)患者的疗效和安全性。在本文中,我们将回顾PDE4B抑制剂在治疗与自身免疫性疾病相关的ILD方面的潜力,包括迄今为止获得的临床前和早期临床数据。
{"title":"Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.","authors":"Flavia V Castelino, Ayodeji Adegunsoye","doi":"10.55563/clinexprheumatol/yg6rck","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/yg6rck","url":null,"abstract":"<p><p>Patients with autoimmune disease-related interstitial lung disease may develop pulmonary fibrosis, which may become progressive. Progressive pulmonary fibrosis (PPF) is associated with poor outcomes. Antifibrotic therapies have shown efficacy as treatments for PPF in patients with autoimmune diseases, but new treatments are needed to slow or halt disease progression. Phosphodiesterases (PDEs) are enzymes that mediate the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Pre-clinical data suggest that preferential inhibition of PDE4B has the potential to slow the progression of pulmonary fibrosis by inhibiting inflammatory and fibrotic pathways, with a lower risk of gastrointestinal adverse events than associated with pan-PDE4 inhibitors. Nerandomilast (BI 1015550) is a preferential PDE4 inhibitor that has demonstrated anti-inflammatory and antifibrotic effects in pre-clinical studies. In a phase II trial in patients with idiopathic pulmonary fibrosis, nerandomilast (given alone or on top of background antifibrotic therapy) prevented a decrease in lung function over 12 weeks with an acceptable safety and tolerability profile. The phase III FIBRONEER-ILD trial is evaluating the efficacy and safety of nerandomilast, given alone or on top of nintedanib, in patients with PPF, including PPF associated with autoimmune diseases. In this article, we review the potential of PDE4B inhibition in the treatment of ILD associated with autoimmune diseases, including the pre-clinical and early clinical data available to date.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104901","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}