Seminars in arthritis and rheumatism最新文献_第10页

Efficacy and safety of abatacept in preclinical rheumatoid arthritis: A systematic review and meta-analysis of randomized controlled trials 阿帕他赛在临床前类风湿性关节炎中的疗效和安全性：随机对照试验的系统回顾和荟萃分析。

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-10-04 DOI: 10.1016/j.semarthrit.2024.152562

Maheen Asif , Aliza Asif , Ummi Aiman Rahman , Abdullah Haseeb , Uzair Jafar , Hareem Farooq

Objective

Abatacept is a biological DMARD that has been used for the treatment of rheumatoid arthritis. However, the literature on its use in preclinical Rheumatoid arthritis (RA) is limited. We conducted this meta-analysis to evaluate the safety and efficacy of abatacept in preclinical RA.

Study design

This meta-analysis intends to assess the effectiveness and safety of abatacept in persons who are at a high risk of developing rheumatoid arthritis (RA) during the pre-clinical phase. The analysis comprises of three randomized controlled trials (RCTs) involving atotal of 367 participants. The study follows the procedures specified in the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA statemen

Results

The meta-analysis found that abatacept significantly reduced the risk of developing RA compared to placebo (RR: 0.67; 95 % CI: 0.51 to 0.89; P = 0.006) and improved tender joint count (SMD: -0.40; 95 % CI: -0.63 to -0.18; P = 0.0004). Additionally, abatacept demonstrated a significant reduction in functional disability (SMD: -1.51; 95 % CI: -1.91 to -1.11; P < 0.00001), though no significant difference was observed in pain reduction. Safety analysis revealed no significant differences in the occurrence of infections, malignancy, or discontinuation due to adverse events between the abatacept and placebo groups.

Conclusion

Abatacept is a promising treatment option for slowing down the development of RA in people who are at high risk. It has a positive safety profile. Additional studies with extended follow-up periods are required to validate these findings and offer more substantial data.

研究目的阿巴他赛普是一种生物 DMARD，已被用于治疗类风湿性关节炎。然而，有关其在临床前类风湿性关节炎（RA）中应用的文献十分有限。我们进行了这项荟萃分析，以评估阿帕赛普在临床前 RA 中的安全性和有效性：本荟萃分析旨在评估阿帕他赛在临床前阶段对类风湿性关节炎（RA）高危人群的有效性和安全性。该分析包括三项随机对照试验（RCT），共有367人参与。结果：荟萃分析发现，与安慰剂相比，阿帕他赛能显著降低罹患RA的风险（RR：0.67；95 % CI：0.51~0.89；P = 0.006），并能改善关节触痛数（SMD：-0.40；95 % CI：-0.63~-0.18；P = 0.0004）。此外，阿帕他赛还能显著减少功能性残疾（SMD：-1.51；95 % CI：-1.91至-1.11；P <0.00001），但在减轻疼痛方面未观察到显著差异。安全性分析显示，阿帕他赛普特组和安慰剂组在感染、恶性肿瘤或因不良事件而停药方面没有明显差异：结论：阿巴特赛普是一种很有前景的治疗方案，可延缓高危人群的RA发展。阿巴他赛普的安全性良好。要验证这些研究结果并提供更多实质性数据，还需要进行更多延长随访期的研究。

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引用次数: 0

Cardiovascular safety of the class of JAK inhibitors or tocilizumab compared with TNF inhibitors in patients with rheumatoid arthritis: Systematic review and a traditional and Bayesian network meta-analysis of randomized clinical trials 与 TNF 抑制剂相比，JAK 抑制剂或托珠单抗类药物对类风湿性关节炎患者心血管的安全性：随机临床试验的系统综述及传统和贝叶斯网络荟萃分析。

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-10-02 DOI: 10.1016/j.semarthrit.2024.152563

Alisson Pugliesi , Daniela Gomes Chicre Oliveira , Vani Abreu de Souza Filho , Júlia de Oliveira Machado , Aline Gonçalves Pereira , Júlia de Castro Silveira Bichuette , Zoraida Sachetto , Luiz Sérgio F. de Carvalho , Manoel Barros Bertolo

Background

We aimed to compare the risk of major adverse cardiovascular events (MACE) and all-cause of death (ACD) in patients with rheumatoid arthritis (RA) treated with JAK inhibitors (JAKi) or tocilizumab (TCZ) versus tumor necrosis factor (TNF) inhibitors (TNFi).

Methods

We performed a systematic review of six medical databases until May, 2024 for phase 2–4 randomized controlled trials (RCTs) evaluating patients with RA treated with TCZ or JAKi (intervention arm) compared with controls (TNFi or placebo). The study data were independently assessed by 3 investigators. The risk of bias was assessed using the Cochrane Collaboration tool. We performed a network meta-analysis with random effects to evaluate the risk of MACE (primary outcome) and ACD (secondary outcome) compared to TNFi. We also calculated the posterior probability of increasing the primary and secondary outcomes by 15% or more (PP_15%) following Bayes' theorem.

Results

This meta-analysis included 18 RCTs with 21,432 patients and 57,040 patient-years. JAKi were linked to a non-statistically significant increase in the risk of MACE and ACD as compared to TNFi (ORs of 1.232 [95%CI 0.86–1.76]; p = 0.56 and ORs = 1.3903[95%CI 0.94–2.07]; p = 0.10, respectively). By Bayesian analysis, a high clinical probability of more frequent MACE (PP_15% of 61%) and ACD (PP_15% of 84%) was found in the JAKi group than in the TNFi group. No statistical difference was found between TCZ and TNFi in relation to MACE (1.029 [95%CI 0.75 -1.40]; p = 0.86) and ACD (1.072 [95%CI 0.78–1.48]; p = 0.67]) in the traditional meta-analysis. In the Bayesian approach, the probability of a difference in clinical relevance was low (PP_15% for MACE of 11% and PP_15% for ACD of 25%).

Discussion

The main limitation of this study is the small number of events with JAKi other than tofacitinib, reflecting the importance of ORAL SURVEILLANCE. Despite this, these data reinforce the recommendations of regulatory agencies and rheumatology societies on the use of JAKi in the context of RA, but above all call for more direct comparison studies involving primary safety outcomes with JAKi, since the outcome data available are still small and heterogeneous. In both meta-analyses, no difference was found between TNFi and TCZ.

背景：我们旨在比较类风湿关节炎（RA）患者接受JAK抑制剂（JAKi）或妥西珠单抗（TCZ）治疗与肿瘤坏死因子（TNF）抑制剂（TNFi）治疗的主要不良心血管事件（MACE）和全因死亡（ACD）风险：我们对截至2024年5月的6个医学数据库进行了系统性回顾，以了解2-4期随机对照试验（RCT）的情况，这些试验评估了接受TCZ或JAKi（干预组）治疗的RA患者与对照组（TNFi或安慰剂）的对比情况。研究数据由3名研究人员独立评估。偏倚风险采用 Cochrane 协作工具进行评估。我们采用随机效应进行了网络荟萃分析，以评估与 TNFi 相比发生 MACE（主要结局）和 ACD（次要结局）的风险。我们还根据贝叶斯定理计算了主要和次要结局增加15%或更多的后验概率（PP15%）：这项荟萃分析包括18项RCT，共21432名患者，57040个患者年。与 TNFi 相比，JAKi 与 MACE 和 ACD 风险的增加无统计学意义（ORs 分别为 1.232[95%CI 0.86-1.76]；P = 0.56 和 ORs = 1.3903[95%CI 0.94-2.07]；P = 0.10）。通过贝叶斯分析，发现JAKi组比TNFi组临床上发生MACE（PP15%，61%）和ACD（PP15%，84%）的概率更高。在传统荟萃分析中，TCZ和TNFi在MACE（1.029 [95%CI 0.75 -1.40]; p = 0.86）和ACD（1.072 [95%CI 0.78-1.48]; p = 0.67]）方面没有统计学差异。在贝叶斯方法中，临床相关性差异的概率较低（MACE的PP15%为11%，ACD的PP15%为25%）：本研究的主要局限性在于使用托法替尼以外的 JAKi 发生的事件较少，这反映了口服检查的重要性。尽管如此，这些数据还是加强了监管机构和风湿病学会关于在RA情况下使用JAKi的建议，但最重要的是，由于现有的结果数据仍然较少且异质性较强，因此需要进行更多涉及JAKi主要安全性结果的直接比较研究。在两项荟萃分析中，均未发现TNFi与TCZ之间存在差异。

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引用次数: 0

Neuropathic pain in spondyloarthritis: Decoding its prevalence, risk factors, and impact on disease activity 脊柱关节炎的神经性疼痛：解码脊柱关节炎神经痛的发病率、风险因素及其对疾病活动的影响。

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-27 DOI: 10.1016/j.semarthrit.2024.152557

Giuseppe Lopalco , Sergio Del Vescovo , Maria Morrone , Andrea Cito , Marco Fornaro , Eugenio Capparelli , Eneida Cela , Maria Sole Chimenti , Florenzo Iannone

Objectives

This study aimed to evaluate the prevalence and characteristics of neuropathic pain in patients with various subtypes of spondyloarthritis (SpA), including axial SpA (axSpA), psoriatic arthritis (PsA), and undifferentiated peripheral SpA (p-SpA). Additionally, the study sought to identify potential risk factors associated with the presence or severity of neuropathic pain and to investigate its impact on clinical disease activity assessment.

Methods

We conducted a cross-sectional study at two tertiary rheumatology centers, enrolling patients diagnosed with SpA. Data on demographic and clinical characteristics, comorbidities, and current therapies were collected. Neuropathic pain was assessed using the PainDETECT Questionnaire (PD-Q) and the Neuropathic Pain Symptom Inventory (NPSI). Statistical analyses included descriptive statistics, t-tests, and Pearson's correlations to evaluate the relationships between neuropathic pain scores and clinical disease activity indices.

Results

The study included 177 patients. Of these, 22.2% had a PD-Q score ≥19, showing a high likelihood of neuropathic pain, while 64.9% scored ≤12, suggesting the absence of significant neuropathic components. The mean PD-Q score was 11.5 ± 10.1. Subgroup analyses showed that females had significantly higher scores for paroxysmal and evoked pain (p < 0.05), and obese patients had significantly higher scores across all NPSI subscores (p < 0.05). Moderate positive correlations were found between neuropathic pain scores and clinical disease activity indices, such as DAPSA (r = 0.46, p < 0.0001) and ASDAS-CRP (r = 0.42, p < 0.01).

Conclusions

Neuropathic pain is prevalent among patients with SpA and is significantly associated with disease activity assessments and management. This study highlights the importance of integrating neuropathic pain evaluation into the clinical assessment of SpA to tailor treatment approaches effectively and improve patient outcomes.

研究目的本研究旨在评估脊柱关节炎（SpA）各种亚型患者中神经病理性疼痛的患病率和特征，包括轴性脊柱关节炎（axSpA）、银屑病关节炎（PsA）和未分化外周性脊柱关节炎（p-SpA）。此外，该研究还试图找出与神经病理性疼痛的存在或严重程度相关的潜在风险因素，并调查其对临床疾病活动性评估的影响：我们在两家三级风湿病学中心开展了一项横断面研究，招募了确诊为 SpA 的患者。我们收集了有关人口统计学和临床特征、合并症和当前疗法的数据。神经病理性疼痛采用疼痛DETECT问卷（PD-Q）和神经病理性疼痛症状量表（NPSI）进行评估。统计分析包括描述性统计、t 检验和皮尔逊相关性，以评估神经病理性疼痛评分与临床疾病活动指数之间的关系：研究共纳入 177 名患者。其中22.2%的患者PD-Q评分≥19分，显示神经病理性疼痛的可能性很高，而64.9%的患者评分≤12分，表明没有明显的神经病理性成分。PD-Q平均得分为11.5 ± 10.1。亚组分析显示，女性阵发性疼痛和诱发痛的得分明显更高（P < 0.05），肥胖患者在所有 NPSI 子评分中的得分明显更高（P < 0.05）。神经病理性疼痛评分与临床疾病活动指数（如 DAPSA（r = 0.46，p < 0.0001）和 ASDAS-CRP（r = 0.42，p < 0.01））之间呈中度正相关：神经性疼痛在 SpA 患者中很普遍，与疾病活动性评估和管理密切相关。这项研究强调了将神经性疼痛评估纳入SpA临床评估的重要性，以便有效地调整治疗方法，改善患者预后。

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引用次数: 0

Efficacy and safety of a step-down regimen of low dosage of glucocorticoids combined with early administration of synthetic or biologic immunosuppressants in anti-synthetase syndrome: A pilot study 低剂量糖皮质激素联合早期使用合成或生物免疫抑制剂的降级方案在抗合成酶综合征中的有效性和安全性：一项试点研究。

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-24 DOI: 10.1016/j.semarthrit.2024.152560

Edoardo Conticini , Paolo Cameli , Silvia Grazzini , Miriana d'Alessandro , Laura Bergantini , Brunetta Porcelli , Maria Antonietta Mazzei , Luca Cantarini , Elena Bargagli , Bruno Frediani

Introduction

Anti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of anti-aminoacyl-transfer-RNA synthetase antibodies (ARS) and the involvement of muscles, skin, joints, and lungs. Despite increasing interest and evidence, optimal clinical management remains unclear due to a lack of randomized control trials. This study aims to evaluate the efficacy and safety of a treatment regimen involving early co-administration of glucocorticoids and immunosuppressants, with rapid prednisone tapering.

Materials and methods

We prospectively enrolled patients referred to our multidisciplinary “Myositis Clinic” with a diagnosis of ASS. Clinical, serological, instrumental and medications data were collected at baseline and at 6 and 12 months follow-up. According to treatment protocol, patients were treated with traditional synthetic immunosuppressants or rituximab (RTX) depending on clinical manifestations. Prednisone (PDN) was gradually tapered and eventually discontinued within 6 or 12 months.

Results

A total of twenty-seven subjects were enrolled: arthritis, myositis and ILD were assessed in 9, 16 and 18 patients, respectively, and all of them had an active disease. RTX was administered after methotrexate (MTX) in 4 cases of refractory joint involvement and co-administration of a second immunosuppressant was necessary in 2 patients. When muscle involvement was present, first-line therapy was MTX, followed by mycophenolate mofetil (MMF) or RTX, which allowed to achieve low disease activity or remission, respectively. Eight ILD-patients were treated with MMF and switched to RTX in 5 cases of inefficacy, but all patients were in clinical remission at the end of follow-up. At 12 months, 12 patients discontinued PDN.

Conclusions

This study is the first to prospectively report on the efficacy and safety of a stepwise, steroid-sparing treatment ASS encompassing various domains. MTX, as well as other synthetic immunosuppressants, showed limited efficacy in ASS-related arthritis, while RTX emerged as a promising option. This study recommends early RTX use in case of arthritis, suggesting it as a pivotal treatment for ILD too, and raises questions regarding maintenance therapy and treatment-free remission.

简介：抗合成酶综合征（ASS）是一种罕见的自身免疫性疾病：抗合成酶综合征（ASS）是一种罕见的自身免疫性疾病，其特点是存在抗氨基酸转移-RNA 合成酶抗体（ARS），并累及肌肉、皮肤、关节和肺部。尽管人们对该病的兴趣与日俱增，证据也越来越多，但由于缺乏随机对照试验，最佳临床治疗方法仍不明确。本研究旨在评估早期联合应用糖皮质激素和免疫抑制剂并快速减量泼尼松的治疗方案的有效性和安全性：我们对转诊到我们的多学科 "肌炎诊所 "并诊断为 ASS 的患者进行了前瞻性登记。我们收集了基线、6 个月和 12 个月随访时的临床、血清学、仪器和药物数据。按照治疗方案，患者根据临床表现接受传统合成免疫抑制剂或利妥昔单抗（RTX）治疗。泼尼松（PDN）逐渐减量，最终在6个月或12个月内停用：共有 27 名受试者：分别有 9、16 和 18 名患者接受了关节炎、肌炎和 ILD 评估，所有患者的病情均处于活动期。4例难治性关节受累患者在使用甲氨蝶呤（MTX）后使用了RTX，2例患者需要联合使用第二种免疫抑制剂。当出现肌肉受累时，一线疗法是MTX，然后是霉酚酸酯（MMF）或RTX，这两种疗法可分别实现低疾病活动度或缓解。8名ILD患者接受了MMF治疗，5名疗效不佳的患者转为RTX治疗，但所有患者在随访结束时均临床缓解。12个月后，12名患者停止了PDN治疗：这项研究首次前瞻性地报告了包括各个领域的逐步类固醇节省治疗 ASS 的有效性和安全性。MTX和其他合成免疫抑制剂对ASS相关关节炎的疗效有限，而RTX则是一种很有前途的选择。这项研究建议在关节炎患者中尽早使用 RTX，并将其作为治疗 ILD 的关键药物，同时还提出了有关维持治疗和无治疗缓解的问题。

{"title":"Efficacy and safety of a step-down regimen of low dosage of glucocorticoids combined with early administration of synthetic or biologic immunosuppressants in anti-synthetase syndrome: A pilot study","authors":"Edoardo Conticini , Paolo Cameli , Silvia Grazzini , Miriana d'Alessandro , Laura Bergantini , Brunetta Porcelli , Maria Antonietta Mazzei , Luca Cantarini , Elena Bargagli , Bruno Frediani","doi":"10.1016/j.semarthrit.2024.152560","DOIUrl":"10.1016/j.semarthrit.2024.152560","url":null,"abstract":"<div><h3>Introduction</h3><div>Anti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of anti-aminoacyl-transfer-RNA synthetase antibodies (ARS) and the involvement of muscles, skin, joints, and lungs. Despite increasing interest and evidence, optimal clinical management remains unclear due to a lack of randomized control trials. This study aims to evaluate the efficacy and safety of a treatment regimen involving early co-administration of glucocorticoids and immunosuppressants, with rapid prednisone tapering.</div></div><div><h3>Materials and methods</h3><div>We prospectively enrolled patients referred to our multidisciplinary “Myositis Clinic” with a diagnosis of ASS. Clinical, serological, instrumental and medications data were collected at baseline and at 6 and 12 months follow-up. According to treatment protocol, patients were treated with traditional synthetic immunosuppressants or rituximab (RTX) depending on clinical manifestations. Prednisone (PDN) was gradually tapered and eventually discontinued within 6 or 12 months.</div></div><div><h3>Results</h3><div>A total of twenty-seven subjects were enrolled: arthritis, myositis and ILD were assessed in 9, 16 and 18 patients, respectively, and all of them had an active disease. RTX was administered after methotrexate (MTX) in 4 cases of refractory joint involvement and co-administration of a second immunosuppressant was necessary in 2 patients. When muscle involvement was present, first-line therapy was MTX, followed by mycophenolate mofetil (MMF) or RTX, which allowed to achieve low disease activity or remission, respectively. Eight ILD-patients were treated with MMF and switched to RTX in 5 cases of inefficacy, but all patients were in clinical remission at the end of follow-up. At 12 months, 12 patients discontinued PDN.</div></div><div><h3>Conclusions</h3><div>This study is the first to prospectively report on the efficacy and safety of a stepwise, steroid-sparing treatment ASS encompassing various domains. MTX, as well as other synthetic immunosuppressants, showed limited efficacy in ASS-related arthritis, while RTX emerged as a promising option. This study recommends early RTX use in case of arthritis, suggesting it as a pivotal treatment for ILD too, and raises questions regarding maintenance therapy and treatment-free remission.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"69 ","pages":"Article 152560"},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The link between traumatic stress and autoimmune rheumatic diseases: A systematic scoping review 创伤压力与自身免疫性风湿病之间的联系：系统性范围审查

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-21 DOI: 10.1016/j.semarthrit.2024.152558

Markus Ploesser , Stuart Silverman , Jose Daniel Lomeli Diaz , Miriam Tanja Zincke , Mihaela B. Taylor

Background

The impact of traumatic stress on autoimmune rheumatic diseases (ARDs) has been largely overlooked in existing research. This scoping review aimed to systematically examine the research literature relating to the relationship between traumatic stress and ARDs, by identifying study designs, methodologies, and gaps in the current research landscape.

Methods

The following databases and search interfaces were searched on 15th December 2023: Embase (via Embase.com), Medline (via PubMed), and Web of Science. Additional references were identified via bibliographies of included studies. The following studies were included, with no publication date limit and language restricted to English: targeting the association between traumatic stress and ARDs, observational methodologies, including cohort, case-control, and cross-sectional studies, exclusively focusing on self-reported psychological trauma impacts, such as adverse childhood experiences (ACEs), Post-traumatic Stress Disorder (PTSD), or major life stressors. Two authors independently assessed the studies for inclusion criteria and extracted the data.

Results

This scoping review revealed connections between traumatic stress and ARDs through an analysis of 21 included studies, highlighting the scarcity of research in this area. The studies, primarily from high-income countries and especially the USA, span from 2000 to 2023, indicating a growing interest in recent years and employing a range of methodologies. Traumas such as ACEs, PTSD, and major life events were frequently examined, showing a strong association with an increased risk and severity of ARDs, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Conclusion

This scoping review reveals a notable dearth in research on the impact of traumatic stress, such as ACEs, PTSD, and major life events, on ARDs, especially on rare diseases, yet underscores a significant association between trauma and ARD severity or incidence. It highlights the critical need for future investigations to broaden the scope of ARDs studied, extend research to less represented regions, and utilize diverse, standardized methodologies to deepen our understanding of the trauma-ARD association.

背景现有研究在很大程度上忽视了创伤应激对自身免疫性风湿病（ARD）的影响。本范围综述旨在通过确定研究设计、方法和当前研究中的空白点，系统地审查与创伤应激和 ARDs 之间关系有关的研究文献。方法于 2023 年 12 月 15 日检索了以下数据库和检索界面：于 2023 年 12 月 15 日检索了以下数据库和检索界面：Embase（通过 Embase.com）、Medline（通过 PubMed）和 Web of Science。通过所纳入研究的参考书目确定了其他参考文献。纳入的研究没有出版日期限制，语言仅限于英语：针对创伤压力与 ARDs 之间的关联，采用观察法，包括队列、病例对照和横断面研究，专门关注自我报告的心理创伤影响，如不良童年经历 (ACE)、创伤后应激障碍 (PTSD) 或主要生活压力源。两位作者独立评估了研究的纳入标准并提取了数据。结果该范围综述通过对 21 项纳入研究的分析，揭示了创伤压力与 ARDs 之间的联系，凸显了该领域研究的稀缺性。这些研究主要来自高收入国家，尤其是美国，时间跨度从 2000 年到 2023 年，表明近年来人们对该领域的研究兴趣日益浓厚，并采用了多种研究方法。ACE、创伤后应激障碍和重大生活事件等创伤经常被研究，这些创伤与 ARD（尤其是类风湿性关节炎（RA）和系统性红斑狼疮（SLE））风险和严重程度的增加有着密切的联系。该研究强调，未来的调查亟需扩大所研究的急性损伤性关节炎的范围，将研究扩展到代表性较低的地区，并利用多样化、标准化的方法加深我们对创伤与急性损伤性关节炎关系的理解。

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引用次数: 0

Post-hoc analysis of two gout remission definitions in a two-year randomized controlled trial of nurse-led versus usual gout care 在为期两年的护士指导与常规痛风护理随机对照试验中，对两种痛风缓解定义的事后分析

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-18 DOI: 10.1016/j.semarthrit.2024.152555

Adwoa Dansoa Tabi-Amponsah , Michael Doherty , Aliya Sarmanova , Weiya Zhang , Sarah Stewart , William J Taylor , Lisa K Stamp , Nicola Dalbeth

Objective

To compare the performance of the 2016 preliminary gout remission definition and a simplified gout remission definition in a clinical trial of nurse-led gout care.

Methods

Data from a 2-year parallel arm, non-blinded, randomised controlled trial of 517 community-derived people with gout were analyzed. Participants were assigned 1:1 to receive nurse-led care or general practitioner usual care. Remission was defined using the 2016 preliminary gout remission definition and a simplified gout remission definition without patient reported outcomes. Binary logistic regression was used to compare intervention groups. General linear models were used to compare Gout Impact Scale (GIS) scores between those in remission and those not in remission using either definition.

Results

Participants in the nurse-led care group were more likely to achieve remission using either definition; at Year 2 the odds ratio was 7.92 [95 % CI 4.86–12.92] using the 2016 preliminary definition and 11.88 [95 % CI 7.49–18.84] using the simplified definition. For all participants, the 2016 preliminary definition was fulfilled by 9.9 % at Year 1 and 28.4 % at Year 2, p < 0.001 and the simplified definition was fulfilled by 17.6 % at Year 1 and 42.7 % at Year 2, p < 0.001. People in remission using either definition had better gout outcomes assessed using the GIS, including greater control over their gout.

Conclusion

Both definitions discriminated between the intervention groups and showed high construct validity. The simplified definition identified more people as being in gout remission at Year 1 and Year 2. The simplified definition is a feasible and valid option for defining gout remission.

目的比较2016年初步痛风缓解定义和简化痛风缓解定义在护士主导的痛风护理临床试验中的表现。方法分析了一项为期2年、由517名社区痛风患者参加的平行臂、非盲法、随机对照试验的数据。参与者按1:1的比例被分配接受护士指导的护理或全科医生的常规护理。缓解采用2016年痛风缓解初步定义和简化痛风缓解定义，不含患者报告结果。二元逻辑回归用于比较干预组。结果无论采用哪种定义，护士主导护理组的参与者都更有可能实现缓解；在第二年，采用2016年初步定义的几率比为7.92 [95 % CI 4.86-12.92]，而采用简化定义的几率比为11.88 [95 % CI 7.49-18.84]。在所有参与者中，符合 2016 年初步定义的人数在第一年占 9.9%，在第二年占 28.4%，p <0.001；符合简化定义的人数在第一年占 17.6%，在第二年占 42.7%，p <0.001。结论两种定义都能区分干预组，并显示出较高的构建有效性。简化定义可识别出更多在第一年和第二年处于痛风缓解期的患者。简化定义是定义痛风缓解的一个可行且有效的选择。

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引用次数: 0

Utility of factor D and other alternative complement factors as biomarkers in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) D因子和其他替代性补体因子作为系统性硬化症相关性肺动脉高压（SSc-PAH）生物标志物的效用

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-13 DOI: 10.1016/j.semarthrit.2024.152554

Eva Petrow , Changyong Feng , Ashley Frazer-Abel , Roberta Goncalves Marangoni , Katie Lutz , William C. Nichols , V. Michael Holers , Christopher Ritchlin , R. James White III , Benjamin D. Korman

Background

Activation of the complement cascade is thought to play a role in scleroderma vasculopathy. We previously showed that complement factor D was elevated in patients with limited cutaneous SSc and pulmonary arterial hypertension (PAH). In this study, we sought to assess multiple relevant components of the complement cascade to determine if they are altered in SSc-PAH, as well as their potential utility as biomarkers of disease severity and progression.

Methods

Complement components (n = 14) were measured using multiplex assays in 156 patients with SSc-PAH from a multi-site repository and were compared to 33 patients with SSc without PAH, and 40 healthy controls. Data were evaluated for correlations between complement levels, right heart catheterization measures, and clinical endpoints including 6-minute walk distance. To assess complement longitudinally, serum complement levels were assayed at 0, 4, 12, 24, 36 and 48 weeks in 52 SSc-PAH patients who participated in a prior clinical trial.

Results

We found that factor D was significantly elevated in SSc-PAH compared to SSc without PAH (p < 0.0001) and was highly sensitive and specific for SSc-PAH (AUC=0.82, p < 0.001). In SSc-PAH patients, alterations in factor H, C4, and factor D were associated with measures of PAH disease severity including right heart catheterization measurements (cardiac output, right atrial pressure, and VO2 max), survival, and 6-minute walk distance. No significant changes in complement levels or clinical associations were seen over time or associated with treatment in the longitudinal clinical trial study.

Conclusion

Our work confirms prior studies demonstrating a role for complement activation in SSc vascular disease and elevations of factor D in a large SSc-PAH population. Further, factor H and other complement factors are associated with severity of PAH including mortality. Taken together, these findings suggest that the alternative complement pathway plays a role in SSc-PAH pathogenesis and may serve as a biomarker to inform diagnosis and prognosis.

背景补体级联的激活被认为在硬皮病血管病变中发挥作用。我们以前的研究表明，局限性皮肤SSc和肺动脉高压（PAH）患者的补体因子D升高。在这项研究中，我们试图评估补体级联的多种相关成分，以确定它们在 SSc-PAH 中是否发生了改变，以及它们作为疾病严重程度和进展的生物标记物的潜在作用。方法：使用多重检测法测量了来自多站资料库的 156 名 SSc-PAH 患者的补体成分（n = 14），并与 33 名无 PAH 的 SSc 患者和 40 名健康对照组进行了比较。对数据进行了评估，以确定补体水平、右心导管测量和临床终点（包括 6 分钟步行距离）之间的相关性。结果我们发现，与无 PAH 的 SSc 患者相比，SSc-PAH 患者的因子 D 显著升高（p < 0.0001），并且对 SSc-PAH 具有高度敏感性和特异性（AUC=0.82，p < 0.001）。在SSc-PAH患者中，因子H、C4和因子D的改变与PAH疾病严重程度的测量相关，包括右心导管测量（心输出量、右心房压和最大容氧量）、存活率和6分钟步行距离。在纵向临床试验研究中，补体水平或临床相关性没有随着时间的推移而发生明显变化，也没有与治疗相关联。结论我们的研究证实了之前的研究，这些研究表明补体激活在 SSc 血管疾病中的作用，以及在大量 SSc-PAH 患者中因子 D 的升高。此外，因子 H 和其他补体因子与 PAH 的严重程度（包括死亡率）有关。总之，这些研究结果表明，替代性补体途径在 SSc-PAH 发病机制中起着一定的作用，并可作为一种生物标志物为诊断和预后提供信息。

{"title":"Utility of factor D and other alternative complement factors as biomarkers in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH)","authors":"Eva Petrow , Changyong Feng , Ashley Frazer-Abel , Roberta Goncalves Marangoni , Katie Lutz , William C. Nichols , V. Michael Holers , Christopher Ritchlin , R. James White III , Benjamin D. Korman","doi":"10.1016/j.semarthrit.2024.152554","DOIUrl":"10.1016/j.semarthrit.2024.152554","url":null,"abstract":"<div><h3>Background</h3><p>Activation of the complement cascade is thought to play a role in scleroderma vasculopathy. We previously showed that complement factor D was elevated in patients with limited cutaneous SSc and pulmonary arterial hypertension (PAH). In this study, we sought to assess multiple relevant components of the complement cascade to determine if they are altered in SSc-PAH, as well as their potential utility as biomarkers of disease severity and progression.</p></div><div><h3>Methods</h3><p>Complement components (<em>n</em> = 14) were measured using multiplex assays in 156 patients with SSc-PAH from a multi-site repository and were compared to 33 patients with SSc without PAH, and 40 healthy controls. Data were evaluated for correlations between complement levels, right heart catheterization measures, and clinical endpoints including 6-minute walk distance. To assess complement longitudinally, serum complement levels were assayed at 0, 4, 12, 24, 36 and 48 weeks in 52 SSc-PAH patients who participated in a prior clinical trial.</p></div><div><h3>Results</h3><p>We found that factor D was significantly elevated in SSc-PAH compared to SSc without PAH (<em>p</em> < 0.0001) and was highly sensitive and specific for SSc-PAH (AUC=0.82, <em>p</em> < 0.001). In SSc-PAH patients, alterations in factor H, C4, and factor D were associated with measures of PAH disease severity including right heart catheterization measurements (cardiac output, right atrial pressure, and VO2 max), survival, and 6-minute walk distance. No significant changes in complement levels or clinical associations were seen over time or associated with treatment in the longitudinal clinical trial study.</p></div><div><h3>Conclusion</h3><p>Our work confirms prior studies demonstrating a role for complement activation in SSc vascular disease and elevations of factor D in a large SSc-PAH population. Further, factor H and other complement factors are associated with severity of PAH including mortality. Taken together, these findings suggest that the alternative complement pathway plays a role in SSc-PAH pathogenesis and may serve as a biomarker to inform diagnosis and prognosis.</p></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"69 ","pages":"Article 152554"},"PeriodicalIF":4.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Barriers and facilitators to application of treat-to-target management in psoriatic arthritis and axial spondyloarthritis in practice: A systematic literature review 银屑病关节炎和轴性脊柱关节炎在实践中应用 "靶向治疗 "管理的障碍和促进因素：系统性文献综述

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-07 DOI: 10.1016/j.semarthrit.2024.152546

Casper Webers , Ivette Essers , Marin Been , Astrid van Tubergen

Objective

To review the evidence on barriers and facilitators to application of treat-to-target (T2T) in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in daily practice.

Methods

A systematic search was conducted in MEDLINE/Embase up to December 2023, focusing on axSpA/PsA. Any type of quantitative/qualitative original research was eligible for inclusion if barriers or facilitators to application of T2T were explored. In a qualitative synthesis, barriers/facilitators were classified by the level to which they apply (healthcare provider [HCP], patient, organisation).

Results

Of 28 included studies, most focused on PsA (n = 21/28). Studies included patients (n = 23/28), HCP (n = 4/28) or both (n = 1/28). In total, over 25 barriers and 15 facilitators to application of T2T were identified. At the HCP level, most studies focused on the measurement of the target, especially in PsA, highlighting that agreement among instruments was suboptimal. At the patient level, the role of patient-reported outcomes (PROs), while deemed relevant, was shown to act as a barrier to achieve targets that included PRO components. At the organisational level, the increased time and resources needed for T2T were considered a barrier, although it was noted that T2T could also reduce healthcare use and sick leave. Notably, for several components, no facilitators were identified at all.

Conclusion

Various barriers and facilitators were identified, acting on several levels. Data in axSpA were scarce, as was evidence on certain components of T2T. Future research should address these knowledge gaps and explore how these barriers and facilitators could be targeted to improve application of T2T in practice.

目的综述在日常实践中，轴性脊柱关节炎（axSpA）和银屑病关节炎（PsA）应用 "靶向治疗"（T2T）的障碍和促进因素的证据。方法在 MEDLINE/Embase 中进行系统检索，检索时间截至 2023 年 12 月，重点关注 axSpA/PsA。如果探讨了应用 T2T 的障碍或促进因素，则任何类型的定量/定性原创研究均可纳入。在定性综述中，障碍/促进因素按其适用的级别（医疗保健提供者 [HCP]、患者、组织）进行分类。结果在 28 项纳入的研究中，大多数侧重于 PsA（n = 21/28）。研究包括患者（n = 23/28）、医疗保健提供者（n = 4/28）或两者（n = 1/28）。总共发现了超过 25 个应用 T2T 的障碍和 15 个应用 T2T 的促进因素。在 HCP 层面，大多数研究侧重于目标的测量，尤其是在 PsA 中，强调了不同工具之间的一致性并不理想。在患者层面，患者报告结果（PROs）的作用虽然被认为是相关的，但却成为实现包含患者报告结果内容的目标的障碍。在组织层面，虽然 T2T 也能减少医疗使用和病假，但 T2T 所需的时间和资源的增加被认为是一个障碍。值得注意的是，有几项内容根本没有发现促进因素。有关轴索硬化症的数据很少，有关 T2T 某些组成部分的证据也很少。未来的研究应解决这些知识空白，并探索如何针对这些障碍和促进因素改进 T2T 在实践中的应用。

{"title":"Barriers and facilitators to application of treat-to-target management in psoriatic arthritis and axial spondyloarthritis in practice: A systematic literature review","authors":"Casper Webers , Ivette Essers , Marin Been , Astrid van Tubergen","doi":"10.1016/j.semarthrit.2024.152546","DOIUrl":"10.1016/j.semarthrit.2024.152546","url":null,"abstract":"<div><h3>Objective</h3><p>To review the evidence on barriers and facilitators to application of treat-to-target (T2T) in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in daily practice.</p></div><div><h3>Methods</h3><p>A systematic search was conducted in MEDLINE/Embase up to December 2023, focusing on axSpA/PsA. Any type of quantitative/qualitative original research was eligible for inclusion if barriers or facilitators to application of T2T were explored. In a qualitative synthesis, barriers/facilitators were classified by the level to which they apply (healthcare provider [HCP], patient, organisation).</p></div><div><h3>Results</h3><p>Of 28 included studies, most focused on PsA (<em>n</em> = 21/28). Studies included patients (<em>n</em> = 23/28), HCP (<em>n</em> = 4/28) or both (<em>n</em> = 1/28). In total, over 25 barriers and 15 facilitators to application of T2T were identified. At the HCP level, most studies focused on the measurement of the target, especially in PsA, highlighting that agreement among instruments was suboptimal. At the patient level, the role of patient-reported outcomes (PROs), while deemed relevant, was shown to act as a barrier to achieve targets that included PRO components. At the organisational level, the increased time and resources needed for T2T were considered a barrier, although it was noted that T2T could also reduce healthcare use and sick leave. Notably, for several components, no facilitators were identified at all.</p></div><div><h3>Conclusion</h3><p>Various barriers and facilitators were identified, acting on several levels. Data in axSpA were scarce, as was evidence on certain components of T2T. Future research should address these knowledge gaps and explore how these barriers and facilitators could be targeted to improve application of T2T in practice.</p></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"69 ","pages":"Article 152546"},"PeriodicalIF":4.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049017224001860/pdfft?md5=a460802eb02ef773fd33f96733a6962b&pid=1-s2.0-S0049017224001860-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic syndrome, radiographic osteoarthritis progression and chronic pain of the knee among men and women from the general population: The Rotterdam study 普通人群中的代谢综合征、放射学骨关节炎进展和膝关节慢性疼痛：鹿特丹研究

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-07 DOI: 10.1016/j.semarthrit.2024.152544

I.A. Szilagyi , N.L. Nguyen , C.G. Boer , D. Schiphof , F. Ahmadizar , M. Kavousi , S.M.A. Bierma-Zeinstra , J.B.J. van Meurs

Objective

Although a relationship between osteoarthritis and components of metabolic syndrome (MetS) has been suggested, most of the results have been cross-sectional. We, therefore, aimed to investigate the sex-specific longitudinal association of (components of) MetS with progression of radiographic osteoarthritis and chronic pain in the knee joints in a large prospective cohort.

Method

In the large population-based Rotterdam study of up to 6,138 individuals, median follow-up time 5.7 (IQR 5.5) years, we examined the relation between MetS and its components (abdominal obesity, high triglycerides, low high-density lipoprotein, elevated blood pressure, and type 2 diabetes) with the progression of osteoarthritis using generalized estimating equations, generalized linear models and competing risk analysis. Analyses were stratified for sex. Covariates adjusted for: age, smoking, alcohol use, education, sub-cohort, baseline K/L grade, months between radiographs and BMI.

Results

The presence of MetS (37.6 % in men, 39 % in women) and elevated blood pressure was associated with an increased risk of knee osteoarthritis progression in both men and women. MetS was associated with an increased risk of incident chronic knee pain (CKP) in men. In addition, abdominal obesity and high triglycerides showed higher riskfor incidence of CKP in men,but not in women. The associations were attenuated and no longer significant after BMI-adjustment, except for the association of MetS and high triglycerides with incidence of CKP in men that stayed significant (OR 1.04, 95 %CI 1.00–1.07 for MetS and OR 1.04, 95 %CI 1.01–1.07 for high triglycerides).

Conclusion

Metabolic syndrome and individual metabolic components, such as abdominal obesity and elevated blood pressure, were associated with radiographic progression of knee OA in both men and women, but not independent of BMI. Metabolic syndrome and high triglycerides were associated with incidence of CKP only in men.

目的虽然骨关节炎与代谢综合征（MetS）之间存在关系，但大多数结果都是横断面的。因此，我们的目的是在一个大型前瞻性队列中调查 MetS（成分）与膝关节放射学骨关节炎和慢性疼痛进展之间的性别特异性纵向关系。我们使用广义估计方程、广义线性模型和竞争风险分析，研究了 MetS 及其组成部分（腹部肥胖、高甘油三酯、低高密度脂蛋白、血压升高和 2 型糖尿病）与骨关节炎进展之间的关系。分析按性别分层。结果在男性和女性中，MetS（男性为 37.6%，女性为 39%）和血压升高与膝关节骨性关节炎进展风险增加有关。在男性中，MetS 与慢性膝关节疼痛（CKP）的发病风险增加有关。此外，腹部肥胖和高甘油三酯在男性中显示出更高的慢性膝关节痛发病风险，但在女性中却没有。除了 MetS 和高甘油三酯与男性 CKP 发病率的关系仍然显著（MetS 的 OR 值为 1.04，95 %CI 为 1.00-1.07；高甘油三酯的 OR 值为 1.04，95 %CI 为 1.01-1.07）外，其他关系在进行体重指数调整后均有所减弱且不再显著。结论代谢综合征和个别代谢成分，如腹部肥胖和血压升高，与男性和女性膝关节 OA 的影像学进展有关，但与体重指数无关。代谢综合征和高甘油三酯仅与男性的 CKP 发生率有关。

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引用次数: 0

Validation of the ankle-specific pediatric arthritis ultrasound scoring system in children with juvenile idiopathic arthritis 验证幼年特发性关节炎患儿踝关节特异性小儿关节炎超声评分系统

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism

Pub Date : 2024-09-01 DOI: 10.1016/j.semarthrit.2024.152545

Patricia Vega-Fernandez , Kelly Rogers , Pinar Ozge Avar-Aydin , Megan Quinlan-Waters , Jennifer Huggins , Hermine I Brunner , Daniel J. Lovell , Mekibib Altaye , Amy Cassedy , Arthur B Meyers , Tracy V Ting

Objective

To validate the ankle-specific Pediatric Arthritis Ultrasound Scoring System (PAUSS-ankle) in children with juvenile idiopathic arthritis (JIA).

Methods

Patients with a diagnosis of JIA prospectively underwent a standard clinical assessment and musculoskeletal ultrasound (MSUS) of one or both ankles. B-mode and Power-Doppler mode MSUS images were acquired and scored according to the PAUSS-ankle protocol. A subset of patients received a contrast-enhanced MRI (ceMRI) of the affected ankle. ceMRI scoring for synovitis was performed according to the Rheumatoid Arthritis MRI System (RAMRIS). Test characteristics of the PAUSS-ankle scores were evaluated with ceMRI as reference. Associations between the findings on physical examination, PAUSS-ankle, and RAMRIS were investigated.

Results

Thirty-two patients with JIA contributed 63 MSUS and 15 ceMRIs of the ankles. The PAUSS-ankle total B-mode score had a moderate correlation with physical examination findings (correlation (r)=0.43, p < 0.001). The PAUSS-ankle B-mode score ≥1 exhibited a sensitivity of 79 % and specificity of 100 %, demonstrating excellent diagnostic accuracy with an area under the curve (AUC)= 0.89 (confidence intervals, CI, 0.78–1.00) while clinical assessment had a sensitivity of 57 % and AUC= 0.71 (CI: 0.58–0.85). The PAUSS-ankle B-mode score had significant strong correlations (r = 0.68–0.90, p < 0.005) with the RAMRIS for the assessment of disease severity for each joint area and the ankle joint as a whole.

Conclusion

Our findings demonstrate excellent diagnostic accuracy of the PAUSS-ankle in detecting the presence and severity of ankle synovitis when compared to ceMRI. The PAUSS-ankle holds significant promise as an accurate measurement that may complement current clinical standards.

目的在幼年特发性关节炎（JIA）患儿中验证踝关节特异性儿科关节炎超声评分系统（PAUSS-ankle）。方法对确诊为 JIA 的患者进行前瞻性的标准临床评估，并对一侧或双侧踝关节进行肌肉骨骼超声检查（MSUS）。根据 PAUSS-踝关节方案采集 B 型和动力多普勒模式 MSUS 图像并进行评分。一部分患者接受了受累踝关节的对比增强核磁共振成像（ceMRI）检查。ceMRI根据类风湿性关节炎核磁共振成像系统（RAMRIS）对滑膜炎进行评分。以ceMRI为参考，评估了PAUSS-踝关节评分的测试特征。结果32名JIA患者接受了63次MSUS检查和15次ceMRI检查。PAUSS-踝关节B型总分与体格检查结果呈中度相关（相关性（r）=0.43，p <0.001）。PAUSS-足踝 B 型评分≥1 分的灵敏度为 79%，特异性为 100%，显示出极佳的诊断准确性，曲线下面积 (AUC)= 0.89（置信区间，CI，0.78-1.00），而临床评估的灵敏度为 57%，AUC= 0.71（CI：0.58-0.85）。在评估每个关节区域和整个踝关节的疾病严重程度时，PAUSS-踝关节 B 型评分与 RAMRIS 有显著的强相关性（r = 0.68-0.90，p < 0.005）。PAUSS-踝关节作为一种精确的测量方法，有望补充当前的临床标准。

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引用次数: 0