Pub Date : 2024-07-23DOI: 10.1136/rmdopen-2024-004422
Natalia Mena-Vázquez, Fernando Ortiz-Márquez, Teresa Ramírez-García, Pablo Cabezudo-García, Aimara García-Studer, Arkaitz Mucientes-Ruiz, Jose Manuel Lisbona-Montañez, Paula Borregón-Garrido, Patricia Ruiz-Limón, Rocío Redondo-Rodríguez, Sara Manrique-Arija, Laura Cano-García, Pedro J Serrano-Castro, Antonio Fernández-Nebro
Objective: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.
Patients and methods: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA.
Results: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6).
Conclusions: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.
{"title":"Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis.","authors":"Natalia Mena-Vázquez, Fernando Ortiz-Márquez, Teresa Ramírez-García, Pablo Cabezudo-García, Aimara García-Studer, Arkaitz Mucientes-Ruiz, Jose Manuel Lisbona-Montañez, Paula Borregón-Garrido, Patricia Ruiz-Limón, Rocío Redondo-Rodríguez, Sara Manrique-Arija, Laura Cano-García, Pedro J Serrano-Castro, Antonio Fernández-Nebro","doi":"10.1136/rmdopen-2024-004422","DOIUrl":"https://doi.org/10.1136/rmdopen-2024-004422","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.</p><p><strong>Patients and methods: </strong>We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA.</p><p><strong>Results: </strong>The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6).</p><p><strong>Conclusions: </strong>Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752607","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}
Pub Date : 2024-07-23DOI: 10.1136/rmdopen-2024-004484
Anna Molto, Chris Serrand, Sandrine Alonso, Francis Berenbaum, Pascal Claudepierre, Bernard Combe, Laure Gossec, Adeline Ruyssen-Witrand, Alain Saraux, Daniel Wendling, Thierry Lequerre, Maxime Dougados
Background: Inception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying the features that will be associated with a confirmed diagnosis over time is key.
Objectives: To assess the frequency and the predisposing factors for a change of an initial diagnosis in an inception axSpA cohort.
Methods: DESIR is an ongoing national multicentre inception axSpA cohort with currently 12.5 years of follow-up. At the entry visit and confirmed at each visit, the diagnosis of axSpA was based on the opinion of the treating rheumatologist. Follow-up was interrupted in case of a change in this initial diagnosis. Multiple imputation was used to estimate the probability of a change in the initial diagnosis of axSpA for each patient lost to follow-up. Factors predisposing to an unchanged diagnosis of axSpA were then assessed using a multivariate logistic regression model on the imputed data sets.
Results: Of the 708 patients included, over 10 years of follow-up, 45 (6.4%) were excluded due to a diagnosis change and 300 (42.4%) patients were lost to follow-up. Based on the imputation of these 300 patients, a change in their initial axSpA diagnosis was estimated in 42 (14.0%). Factors predisposing to an unchanged initial axSpA diagnosis during follow-up were (ORs (95% CIs)): radiographic sacroiliitis: 17.0 (4.1 to 71.0); psoriasis: 5.3 (2.0 to 14.3); CRP≥6 mg/L: 2.7 (1.3 to 5.3); good NSAID response: 2.5 (1.5 to 4.2); HLA B27+: 2.0 (1.3 to 3.3); anterior chest wall pain: 2.0 (1.2 to 3.3) and female sex: 1.9 (1.2 to 3.0).
Conclusion: These data suggest that a change in diagnosis in recent onset axSpA exists, but is not frequent, and is less likely to occur in the presence of objective features at baseline.
{"title":"Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort.","authors":"Anna Molto, Chris Serrand, Sandrine Alonso, Francis Berenbaum, Pascal Claudepierre, Bernard Combe, Laure Gossec, Adeline Ruyssen-Witrand, Alain Saraux, Daniel Wendling, Thierry Lequerre, Maxime Dougados","doi":"10.1136/rmdopen-2024-004484","DOIUrl":"10.1136/rmdopen-2024-004484","url":null,"abstract":"<p><strong>Background: </strong>Inception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying the features that will be associated with a confirmed diagnosis over time is key.</p><p><strong>Objectives: </strong>To assess the frequency and the predisposing factors for a change of an initial diagnosis in an inception axSpA cohort.</p><p><strong>Methods: </strong>DESIR is an ongoing national multicentre inception axSpA cohort with currently 12.5 years of follow-up. At the entry visit and confirmed at each visit, the diagnosis of axSpA was based on the opinion of the treating rheumatologist. Follow-up was interrupted in case of a change in this initial diagnosis. Multiple imputation was used to estimate the probability of a change in the initial diagnosis of axSpA for each patient lost to follow-up. Factors predisposing to an unchanged diagnosis of axSpA were then assessed using a multivariate logistic regression model on the imputed data sets.</p><p><strong>Results: </strong>Of the 708 patients included, over 10 years of follow-up, 45 (6.4%) were excluded due to a diagnosis change and 300 (42.4%) patients were lost to follow-up. Based on the imputation of these 300 patients, a change in their initial axSpA diagnosis was estimated in 42 (14.0%). Factors predisposing to an unchanged initial axSpA diagnosis during follow-up were (ORs (95% CIs)): radiographic sacroiliitis: 17.0 (4.1 to 71.0); psoriasis: 5.3 (2.0 to 14.3); CRP≥6 mg/L: 2.7 (1.3 to 5.3); good NSAID response: 2.5 (1.5 to 4.2); HLA B27+: 2.0 (1.3 to 3.3); anterior chest wall pain: 2.0 (1.2 to 3.3) and female sex: 1.9 (1.2 to 3.0).</p><p><strong>Conclusion: </strong>These data suggest that a change in diagnosis in recent onset axSpA exists, but is not frequent, and is less likely to occur in the presence of objective features at baseline.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752609","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}
Pub Date : 2024-07-22DOI: 10.1136/rmdopen-2024-004411
Mikhail Volkov, Arieke S B Kampstra, Karin A J van Schie, Anouk G van Mourik, Joanneke C Kwekkeboom, Arnoud de Ru, Peter A van Veelen, Tom W J Huizinga, René E M Toes, Diane van der Woude
Objective: Gut-residing bacteria, such as Escherichia coli, can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance to modified self-proteins leading to the anti-modified protein antibodies (AMPAs), hallmarking seropositive rheumatoid arthritis (RA). Our aim was to determine whether acetylated bacterial proteins can induce AMPA responses cross-reactive to modified self-proteins and be recognised by human AMPA (hAMPA).
Methods: E. coli bacteria were grown under amine starvation to generate endogenously acetylated bacterial proteins. Furthermore, E. coli proteins were acetylated chemically. Recognition of these proteins by hAMPA was analysed by western blotting and ELISA; recognition by B cells carrying a modified protein-reactive B cell receptor (BCR) was analysed by pSyk (Syk phosphorylation) activation assay. C57BL/6 mice were immunised with (modified) bacterial protein fractions, and sera were analysed by ELISA.
Results: Chemically modified bacterial protein fractions contained high levels of acetylated proteins and were readily recognised by hAMPA and able to activate B cells carrying modified protein-reactive BCRs. Likely due to substantially lower levels of acetylation, endogenously acetylated protein fractions were not recognised by hAMPA or hAMPA-expressing B cells. Immunising mice with chemically modified protein fractions induced a strong cross-reactive AMPA response, targeting various modified antigens including citrullinated proteins.
Conclusions: Acetylated bacterial proteins are recognisable by hAMPA and are capable of inducing cross-reactive AMPA in mice. These observations provide the first conceptual evidence for a novel mechanism involving the (endogenous) acetylation of the bacterial proteome, allowing a breach of tolerance to modified proteins and the formation of cross-reactive AMPA.
目的:居住在肠道中的细菌,如大肠杆菌,可以在胺饥饿条件下对其蛋白质组进行乙酰化。据推测,(肠道)微生物组参与了破坏对修饰过的自身蛋白的免疫耐受,从而导致抗修饰蛋白抗体(AMPAs),这是血清阳性类风湿性关节炎(RA)的特征。我们的目的是确定乙酰化细菌蛋白是否能诱导与修饰自身蛋白交叉反应的 AMPA 反应,并被人类 AMPA(hAMPA)识别:方法:在胺饥饿条件下培养大肠杆菌,生成内源性乙酰化细菌蛋白。此外,还对大肠杆菌蛋白质进行了化学乙酰化。hAMPA 对这些蛋白质的识别是通过 Western 印迹和 ELISA 分析的;携带改良蛋白反应性 B 细胞受体(BCR)的 B 细胞的识别是通过 pSyk(Syk 磷酸化)激活试验分析的。用(修饰的)细菌蛋白馏分对 C57BL/6 小鼠进行免疫,并通过 ELISA 对血清进行分析:结果:经化学修饰的细菌蛋白馏分含有大量乙酰化蛋白,很容易被 hAMPA 识别,并能激活携带修饰蛋白反应性 BCR 的 B 细胞。可能是由于乙酰化水平低得多,内源性乙酰化蛋白部分不能被hAMPA或表达hAMPA的B细胞识别。用化学修饰过的蛋白质部分对小鼠进行免疫可诱导强烈的交叉反应 AMPA 反应,靶向各种修饰过的抗原,包括瓜氨酸化蛋白质:乙酰化细菌蛋白可被 hAMPA 识别,并能诱导小鼠产生交叉反应性 AMPA。这些观察结果首次从概念上证明了一种涉及细菌蛋白质组(内源性)乙酰化的新机制,该机制允许破坏对修饰蛋白质的耐受性并形成交叉反应性 AMPA。
{"title":"Acetylated bacterial proteins as potent antigens inducing an anti-modified protein antibody response.","authors":"Mikhail Volkov, Arieke S B Kampstra, Karin A J van Schie, Anouk G van Mourik, Joanneke C Kwekkeboom, Arnoud de Ru, Peter A van Veelen, Tom W J Huizinga, René E M Toes, Diane van der Woude","doi":"10.1136/rmdopen-2024-004411","DOIUrl":"10.1136/rmdopen-2024-004411","url":null,"abstract":"<p><strong>Objective: </strong>Gut-residing bacteria, such as <i>Escherichia coli</i>, can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance to modified self-proteins leading to the anti-modified protein antibodies (AMPAs), hallmarking seropositive rheumatoid arthritis (RA). Our aim was to determine whether acetylated bacterial proteins can induce AMPA responses cross-reactive to modified self-proteins and be recognised by human AMPA (hAMPA).</p><p><strong>Methods: </strong><i>E. coli</i> bacteria were grown under amine starvation to generate endogenously acetylated bacterial proteins. Furthermore, <i>E. coli</i> proteins were acetylated chemically. Recognition of these proteins by hAMPA was analysed by western blotting and ELISA; recognition by B cells carrying a modified protein-reactive B cell receptor (BCR) was analysed by pSyk (Syk phosphorylation) activation assay. C57BL/6 mice were immunised with (modified) bacterial protein fractions, and sera were analysed by ELISA.</p><p><strong>Results: </strong>Chemically modified bacterial protein fractions contained high levels of acetylated proteins and were readily recognised by hAMPA and able to activate B cells carrying modified protein-reactive BCRs. Likely due to substantially lower levels of acetylation, endogenously acetylated protein fractions were not recognised by hAMPA or hAMPA-expressing B cells. Immunising mice with chemically modified protein fractions induced a strong cross-reactive AMPA response, targeting various modified antigens including citrullinated proteins.</p><p><strong>Conclusions: </strong>Acetylated bacterial proteins are recognisable by hAMPA and are capable of inducing cross-reactive AMPA in mice. These observations provide the first conceptual evidence for a novel mechanism involving the (endogenous) acetylation of the bacterial proteome, allowing a breach of tolerance to modified proteins and the formation of cross-reactive AMPA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749053","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}
Pub Date : 2024-07-20DOI: 10.1136/rmdopen-2024-004258
Judith W Heutz, Agnes E M Looijen, Annette H M van der Helm-van Mil, Pascal H P de Jong, Elise van Mulligen
{"title":"Tapering csDMARD or TNFi first: is the risk of flares different for ACPA-positive or ACPA-negative rheumatoid arthritis?","authors":"Judith W Heutz, Agnes E M Looijen, Annette H M van der Helm-van Mil, Pascal H P de Jong, Elise van Mulligen","doi":"10.1136/rmdopen-2024-004258","DOIUrl":"10.1136/rmdopen-2024-004258","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734969","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}
Pub Date : 2024-07-08DOI: 10.1136/rmdopen-2024-004259
Leti van Bodegom-Vos, Theodora P M Vliet Vlieland
The implementation of proven effective pharmacological and non-pharmacological interventions into routine rheumatology practice is a lengthy and complex process. Bridging this gap between research and practice is crucial. Hybrid implementation effectiveness studies, integrating effectiveness and implementation aspects, emerge as a proactive and innovative solution to shorten the process of translation of proven interventions into clinical practice. This viewpoint provides an overview of the various types of hybrid implementation effectiveness studies including examples from rheumatology research practice, explains their pivotal role in speeding up the implementation of rheumatology research results and concludes with practical recommendations for the conduct of hybrid implementation effectiveness studies.
{"title":"Bridging the gap: facilitating the use of rheumatology research results in clinical practice with hybrid implementation effectiveness studies.","authors":"Leti van Bodegom-Vos, Theodora P M Vliet Vlieland","doi":"10.1136/rmdopen-2024-004259","DOIUrl":"10.1136/rmdopen-2024-004259","url":null,"abstract":"<p><p>The implementation of proven effective pharmacological and non-pharmacological interventions into routine rheumatology practice is a lengthy and complex process. Bridging this gap between research and practice is crucial. Hybrid implementation effectiveness studies, integrating effectiveness and implementation aspects, emerge as a proactive and innovative solution to shorten the process of translation of proven interventions into clinical practice. This viewpoint provides an overview of the various types of hybrid implementation effectiveness studies including examples from rheumatology research practice, explains their pivotal role in speeding up the implementation of rheumatology research results and concludes with practical recommendations for the conduct of hybrid implementation effectiveness studies.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559632","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}
Pub Date : 2024-07-02DOI: 10.1136/rmdopen-2024-004164
Andrea Dell'Isola, Filippo Recenti, Martin Englund, Ali Kiadaliri
Objectives: To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references.
Methods: Cohort study using prospectively collected healthcare data from the Skåne region, Sweden (~1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model.
Results: We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4.
Conclusions: Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.
目的确定骨关节炎(OA)患者和无 OA 的匹配参照者 20 年来的多病症轨迹:采用瑞典斯科纳地区(约 140 万居民)前瞻性收集的医疗保健数据进行队列研究。我们提取了 OA 和 67 种常见慢性疾病的诊断结果。我们纳入了2007年12月31日年龄在40岁以上、2008年至2009年期间发生过OA的人群。我们选择了无 OA 的参照者,他们的出生年份、性别、死亡年份或迁居到该地区以外的年份都与我们的参照者相匹配。我们采用基于群体的轨迹模型来捕捉 1998 年至 2019 年的发病率计数轨迹。没有任何合并症的个体被列为参照组,但未被纳入模型中:我们确定了 9846 例 OA 病例(平均年龄:65.9 岁(SD 11.7),女性:58%)和 9846 例匹配参照组。在病例和参照者中,有 1296 人未出现慢性病(无慢性病类)。我们确定了四个等级。在研究开始时,所有等级的慢性病平均数量都较低(≤1)。1 级的多病症进展最慢,在每个等级中都逐渐增加。在随访结束时,1 级的慢性病数量最少(平均值为 2.9(标准差为 1.7)):2.9 (SD 1.7)),而第 4 级最高(9.6 (2.6))。OA的存在与属于1级的调整后相对风险为1.29(1.12,1.48),与4级的调整后相对风险为2.45(2.12,2.83):我们的研究结果表明,患有 OA 的人患严重多病症的风险几乎高出三倍。
{"title":"Twenty-year trajectories of morbidity in individuals with and without osteoarthritis.","authors":"Andrea Dell'Isola, Filippo Recenti, Martin Englund, Ali Kiadaliri","doi":"10.1136/rmdopen-2024-004164","DOIUrl":"10.1136/rmdopen-2024-004164","url":null,"abstract":"<p><strong>Objectives: </strong>To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references.</p><p><strong>Methods: </strong>Cohort study using prospectively collected healthcare data from the Skåne region, Sweden (~1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model.</p><p><strong>Results: </strong>We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4.</p><p><strong>Conclusions: </strong>Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493166","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}
Pub Date : 2024-07-01DOI: 10.1136/rmdopen-2024-004529
Thomas Khoo, Meghna Jani, Hector Chinoy
Fatigue is a common symptom of rheumatic diseases and frequently persists even when patients are in a near-remission state. In seeking options to manage troublesome symptoms such as fatigue, complementary and alternative medicines (CAM) are often used by patients despite a lack of evidence base behind such treatment strategies. CAM use is further promoted by social media and ‘influencer’ marketing without rigorous process to ensure scientific accuracy. One mechanism of recent interest in the CAM market is enhancing cellular pathways of nicotinamide adenine dinucleotide (NAD+), purported to restore mitochondrial function. However, clinical trials of NAD+ pathway supplements lack rigorous trial design, many declare conflicts of interest, and safety data is limited. Ultimately, CAM use by our patients is unavoidable. To adequately inform patients about CAM, we need to keep updated on both the latest scientific literature and social media trends. In so doing, we can then propose to patients how standard-of-care therapies, evidence-based lifestyle modifications and CAM might safely and effectively integrate to form a treatment plan.
{"title":"Is there a role for novel supplements in the management of fatigue in rheumatic diseases?","authors":"Thomas Khoo, Meghna Jani, Hector Chinoy","doi":"10.1136/rmdopen-2024-004529","DOIUrl":"https://doi.org/10.1136/rmdopen-2024-004529","url":null,"abstract":"Fatigue is a common symptom of rheumatic diseases and frequently persists even when patients are in a near-remission state. In seeking options to manage troublesome symptoms such as fatigue, complementary and alternative medicines (CAM) are often used by patients despite a lack of evidence base behind such treatment strategies. CAM use is further promoted by social media and ‘influencer’ marketing without rigorous process to ensure scientific accuracy. One mechanism of recent interest in the CAM market is enhancing cellular pathways of nicotinamide adenine dinucleotide (NAD+), purported to restore mitochondrial function. However, clinical trials of NAD+ pathway supplements lack rigorous trial design, many declare conflicts of interest, and safety data is limited. Ultimately, CAM use by our patients is unavoidable. To adequately inform patients about CAM, we need to keep updated on both the latest scientific literature and social media trends. In so doing, we can then propose to patients how standard-of-care therapies, evidence-based lifestyle modifications and CAM might safely and effectively integrate to form a treatment plan.","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775164","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}
Pub Date : 2024-07-01DOI: 10.1136/rmdopen-2024-004381
Özlem Satirer, Joerg C Henes, Michaela Döring, Till Lesk, Susanne Benseler, Jasmin Beate Kuemmerle-Deschner
Objectives To evaluate the long-term effectiveness and safety of autologous haematopoiesis stem cell transplantation (AHSCT) for severe, refractory autoimmune diseases in paediatric patients. Methods A single-centre study of consecutive children and adolescents with refractory autoimmune diseases undergoing AHSCT was performed. Demographics, clinical, laboratory features, pre-AHSCT medications, disease activity and functional status were captured. The primary outcome was progression-free survival, secondary outcomes included overall survival, disease-specific treatment responses, disease activity at the last follow-up and AHSCT safety. Results The study included seven patients: two systemic sclerosis, one pansclerotic morphoea, one eosinophilic fasciitis, one juvenile dermatomyositis and two patients with systemic juvenile idiopathic arthritis; four women, three men median age at AHSCT of 10 years (7–19), median follow-up post-AHSCT of 17 years. Median progression-free survival and overall survival was 4.2 years (95% CI: 0.98 to 8.3) and 17 years (95% CI: 11.8 to 22.1), respectively. Progression-free survival rates at 1 and 2 years post-AHSCT were 100% and 77%, respectively. All children survived. All patients are in clinical remission, only four require ongoing immunotherapy. Safety: Three experienced infections, including HHV6, Candida and Ralstonia sepsis; one developed a systemic inflammatory response syndrome; two new onset secondary autoimmune diseases including autoimmune haemolytic anaemia, Graves’ disease and one was found to have a breast fibroadenoma. Treatment toxicity: one cyclophosphamide-associated transient renal failure and pericardial effusion, one patient with amenorrhoea/infertility. Conclusions AHSCT was an effective and safe approach for children and adolescents with treatment-refractory autoimmune diseases. The indication and timing of transplantation requires a careful consideration and a multidisciplinary approach. Data are available upon reasonable request.
{"title":"Autologous haematopoiesis stem cell transplantation (AHSCT) for treatment-refractory autoimmune diseases in children","authors":"Özlem Satirer, Joerg C Henes, Michaela Döring, Till Lesk, Susanne Benseler, Jasmin Beate Kuemmerle-Deschner","doi":"10.1136/rmdopen-2024-004381","DOIUrl":"https://doi.org/10.1136/rmdopen-2024-004381","url":null,"abstract":"Objectives To evaluate the long-term effectiveness and safety of autologous haematopoiesis stem cell transplantation (AHSCT) for severe, refractory autoimmune diseases in paediatric patients. Methods A single-centre study of consecutive children and adolescents with refractory autoimmune diseases undergoing AHSCT was performed. Demographics, clinical, laboratory features, pre-AHSCT medications, disease activity and functional status were captured. The primary outcome was progression-free survival, secondary outcomes included overall survival, disease-specific treatment responses, disease activity at the last follow-up and AHSCT safety. Results The study included seven patients: two systemic sclerosis, one pansclerotic morphoea, one eosinophilic fasciitis, one juvenile dermatomyositis and two patients with systemic juvenile idiopathic arthritis; four women, three men median age at AHSCT of 10 years (7–19), median follow-up post-AHSCT of 17 years. Median progression-free survival and overall survival was 4.2 years (95% CI: 0.98 to 8.3) and 17 years (95% CI: 11.8 to 22.1), respectively. Progression-free survival rates at 1 and 2 years post-AHSCT were 100% and 77%, respectively. All children survived. All patients are in clinical remission, only four require ongoing immunotherapy. Safety: Three experienced infections, including HHV6, Candida and Ralstonia sepsis; one developed a systemic inflammatory response syndrome; two new onset secondary autoimmune diseases including autoimmune haemolytic anaemia, Graves’ disease and one was found to have a breast fibroadenoma. Treatment toxicity: one cyclophosphamide-associated transient renal failure and pericardial effusion, one patient with amenorrhoea/infertility. Conclusions AHSCT was an effective and safe approach for children and adolescents with treatment-refractory autoimmune diseases. The indication and timing of transplantation requires a careful consideration and a multidisciplinary approach. Data are available upon reasonable request.","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609157","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}
Pub Date : 2024-07-01DOI: 10.1136/rmdopen-2024-004429
Sofia Ramiro, Cédric Lukas, Louis Bessette, Pendleton Wickersham, Tommaso Panni, Rebecca Bolce, Soyi Liu-Leage, Boris Janos, Michael J Nissen, James Cheng-Chung Wei
Background The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1). To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). Methods This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V ([NCT02696785][1]), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. Results Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. Conclusion This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. Trial registration number [NCT02696785][1]. Data are available on reasonable request. Lilly provides access to all individual participant data collected during the trial, after anonymisation, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02696785&atom=%2Frmdopen%2F10%2F3%2Fe004429.atom
{"title":"Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis","authors":"Sofia Ramiro, Cédric Lukas, Louis Bessette, Pendleton Wickersham, Tommaso Panni, Rebecca Bolce, Soyi Liu-Leage, Boris Janos, Michael J Nissen, James Cheng-Chung Wei","doi":"10.1136/rmdopen-2024-004429","DOIUrl":"https://doi.org/10.1136/rmdopen-2024-004429","url":null,"abstract":"Background The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1). To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). Methods This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V ([NCT02696785][1]), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. Results Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. Conclusion This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. Trial registration number [NCT02696785][1]. Data are available on reasonable request. Lilly provides access to all individual participant data collected during the trial, after anonymisation, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02696785&atom=%2Frmdopen%2F10%2F3%2Fe004429.atom","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609159","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}
Pub Date : 2024-07-01DOI: 10.1136/rmdopen-2024-004481
Cecilia Barnini, Louise Oni, Andreas Kronbichler
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterised by systemic involvement of small-to-medium vessels with necrotising inflammation that, by virtue, can affect all organs. Even though the underlying pathophysiology is still not fully understood, a central role is devoted to autoantibodies against two major neutrophil proteins, either proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA), in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These autoantibodies are able to prime and activate neutrophils that, together with other inflammatory cells such as macrophages, monocytes and the complement system, lead to the observed endothelial injury. Both diseases, GPA and MPA, have a predilection for pulmonary and kidney involvement, with 58.6% and 82.2%1 of adults with AAV presenting with ANCA-glomerulonephritis (GN). The incidence of PR3-ANCA is highest in countries with higher latitudes, and PR3-ANCA vasculitis rarely occurs in Japan and China.2 A significant proportion of patients with ANCA-GN remain negative for ANCA but show signs of kidney disease, which is characterised by the absence or only a faint staining for immunoglobulins or complement. In children, the disease is ultra-rare, meaning precise estimates related to epidemiology are missing; however, the underlying disease pathophysiology is believed to be sufficiently similar to that of adults, with subtle differences reported in the frequency of organ involvement. For example, ANCA-GN in GPA seems to be more common in children than in adults, while a comparable frequency is reported in MPA (figure 1). The largest cohort studies reported from Northern America (40 centres), Europe (three centres) and Asia (two centres) revealed that GPA is almost four times as common as MPA.3 In children enrolled on the A Registry for Children with Vasculitis (ARChiVE) registry from 2004 to 2015, initial treatment among 231 children consisted of corticosteroids (96.5%), cyclophosphamide (75.8%), rituximab (12.1%) and plasma exchange …
{"title":"Course of paediatric ANCA-associated glomerulonephritis: advocating for an age-inclusive approach","authors":"Cecilia Barnini, Louise Oni, Andreas Kronbichler","doi":"10.1136/rmdopen-2024-004481","DOIUrl":"https://doi.org/10.1136/rmdopen-2024-004481","url":null,"abstract":"Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterised by systemic involvement of small-to-medium vessels with necrotising inflammation that, by virtue, can affect all organs. Even though the underlying pathophysiology is still not fully understood, a central role is devoted to autoantibodies against two major neutrophil proteins, either proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA), in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These autoantibodies are able to prime and activate neutrophils that, together with other inflammatory cells such as macrophages, monocytes and the complement system, lead to the observed endothelial injury. Both diseases, GPA and MPA, have a predilection for pulmonary and kidney involvement, with 58.6% and 82.2%1 of adults with AAV presenting with ANCA-glomerulonephritis (GN). The incidence of PR3-ANCA is highest in countries with higher latitudes, and PR3-ANCA vasculitis rarely occurs in Japan and China.2 A significant proportion of patients with ANCA-GN remain negative for ANCA but show signs of kidney disease, which is characterised by the absence or only a faint staining for immunoglobulins or complement. In children, the disease is ultra-rare, meaning precise estimates related to epidemiology are missing; however, the underlying disease pathophysiology is believed to be sufficiently similar to that of adults, with subtle differences reported in the frequency of organ involvement. For example, ANCA-GN in GPA seems to be more common in children than in adults, while a comparable frequency is reported in MPA (figure 1). The largest cohort studies reported from Northern America (40 centres), Europe (three centres) and Asia (two centres) revealed that GPA is almost four times as common as MPA.3 In children enrolled on the A Registry for Children with Vasculitis (ARChiVE) registry from 2004 to 2015, initial treatment among 231 children consisted of corticosteroids (96.5%), cyclophosphamide (75.8%), rituximab (12.1%) and plasma exchange …","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609043","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}