Pub Date : 2025-01-04DOI: 10.1186/s13075-024-03467-7
Suying Liu, Yunjiao Yang, Linna Han, Chengmei He, Mengtao Li, Xinping Tian, Juan Meng, Li Wang, Fengchun Zhang
Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA. We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns. A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern. Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA.
{"title":"Gastrointestinal lesions of eosinophilic granulomatosis with polyangiitis: a prediction model and clinical patterns","authors":"Suying Liu, Yunjiao Yang, Linna Han, Chengmei He, Mengtao Li, Xinping Tian, Juan Meng, Li Wang, Fengchun Zhang","doi":"10.1186/s13075-024-03467-7","DOIUrl":"https://doi.org/10.1186/s13075-024-03467-7","url":null,"abstract":"Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA. We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns. A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern. Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"385 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925008","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 : 2025-01-03DOI: 10.1186/s13075-024-03432-4
Nicoletta Luciano, Elisa Barone, Enrico Brunetta, Alessio D’Isanto, Maria De Santis, Angela Ceribelli, Marta Caprioli, Giacomo M. Guidelli, Daniela Renna, Carlo Selmi
There is still a significant proportion of patients with rheumatoid arthritis (RA) in whom multiple therapeutic lines are ineffective. These cases are defined by the EULAR criteria as Difficult-to-Treat RA (D2T-RA) for which there is limited knowledge of predisposing factors. To identify the clinical features associated with D2T-RA in real-life practice. We retrospectively collected demographic, clinical, and serological data on 458 patients consecutively seen for RA between January 2019 and January 2023. We compared patients fulfilling the D2T-RA criteria with the remaining RA cohort using univariate comparisons and logistic regression to determine the impact of clinical features, comorbidities on outcome variable, adjusted for confounders. Seventy-one/458 (16%) patients fulfilled the 2021 EULAR criteria for D2T-RA with no significant differences for age (median 62 years interquartile range -IQR- 58- 65 vs. 62 IQR 60 – 63 in non-D2T), gender prevalence (23% in both groups) and positivity rates for rheumatoid factors (62% vs. 62% in non-D2T) and Anti-Citrullinated Protein Antibodies (ACPA) (69% vs. 61% in non-D2T). Conversely, D2T-RA cases had significant longer disease duration (median 15 years IQR 13–17 vs. 10 years IQR 9–11 in non-D2T; p < 0.0001). D2T-RA also had more erosions at baseline (24% vs. 11% in non-D2T; p < 0.0001) and higher disease activity index (CDAI) at the last follow up visit (15.7 ± 10.5 vs. 7.5 ± 8.8 in non-D2T; p < 0.0001). D2T-RA cases suffered with higher frequency of obesity (33% vs. 19% in non-D2T, p = 0.021) and fibromyalgia (25% vs. 10% in non-D2T, p < 0.0001). The multivariate analysis confirmed the correlations of D2T-RA with disease duration (Odds ratio -OR- 1.06, 95% confidence interval -CI—1.03–1.09; p < 0.0001), baseline erosions (OR 2.73, 95% CI 1.28–5.82; p = 0.009), obesity (OR 2.22, 95% CI 1.10–4.50; p = 0.026) and fibromyalgia (OR 3.91, 95% CI 1.76–8.70; p = 0.001), independent of age and gender. High disease activity, baseline erosions and disease duration are significantly associated with the D2T phenotype of RA while we confirm the importance of obesity and fibromyalgia.
仍有相当比例的类风湿关节炎（RA）患者，其多种治疗方法无效。这些病例被EULAR标准定义为难治性RA (D2T-RA)，对其易感因素的了解有限。在现实生活中识别与D2T-RA相关的临床特征。我们回顾性收集了2019年1月至2023年1月期间连续观察的458例RA患者的人口学、临床和血清学数据。我们将满足D2T-RA标准的患者与其余RA队列进行比较，采用单因素比较和逻辑回归来确定临床特征、合并症对结果变量的影响，并根据混杂因素进行调整。71 /458例（16%）患者符合2021年D2T-RA的EULAR标准，年龄（中位数为62岁，四分位数范围为-IQR- 58- 65，非d2t为62 IQR- 60 - 63）、性别患病率（两组均为23%）和类风湿因子阳性率（非d2t为62%，非d2t为62%）和抗citrullinated Protein Antibodies （ACPA）阳性率（69%，非d2t为61%）无显著差异。相反，D2T-RA病例的病程明显更长(中位15年IQR 13-17，非d2t患者为10年IQR 9-11；p < 0.0001)。D2T-RA在基线时也有更多的侵蚀(24% vs. 11%；p < 0.0001)，最后一次随访时疾病活动指数（CDAI）较高(15.7±10.5 vs.非d2t组为7.5±8.8；p < 0.0001)。D2T-RA患者肥胖（33% vs.非d2t患者的19%，p = 0.021）和纤维肌痛（25% vs.非d2t患者的10%，p < 0.0001）的发生率更高。多因素分析证实D2T-RA与病程相关(优势比- or - 1.06, 95%可信区间- ci - 1.03 - 1.09；p < 0.0001)，基线侵蚀(OR 2.73, 95% CI 1.28-5.82；p = 0.009)，肥胖(OR 2.22, 95% CI 1.10-4.50；p = 0.026)和纤维肌痛(OR 3.91, 95% CI 1.76-8.70；P = 0.001)，与年龄和性别无关。高疾病活动度、基线侵蚀和疾病持续时间与RA的D2T表型显著相关，同时我们证实肥胖和纤维肌痛的重要性。
{"title":"Obesity and fibromyalgia are associated with Difficult-to-Treat Rheumatoid Arthritis (D2T-RA) independent of age and gender","authors":"Nicoletta Luciano, Elisa Barone, Enrico Brunetta, Alessio D’Isanto, Maria De Santis, Angela Ceribelli, Marta Caprioli, Giacomo M. Guidelli, Daniela Renna, Carlo Selmi","doi":"10.1186/s13075-024-03432-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03432-4","url":null,"abstract":"There is still a significant proportion of patients with rheumatoid arthritis (RA) in whom multiple therapeutic lines are ineffective. These cases are defined by the EULAR criteria as Difficult-to-Treat RA (D2T-RA) for which there is limited knowledge of predisposing factors. To identify the clinical features associated with D2T-RA in real-life practice. We retrospectively collected demographic, clinical, and serological data on 458 patients consecutively seen for RA between January 2019 and January 2023. We compared patients fulfilling the D2T-RA criteria with the remaining RA cohort using univariate comparisons and logistic regression to determine the impact of clinical features, comorbidities on outcome variable, adjusted for confounders. Seventy-one/458 (16%) patients fulfilled the 2021 EULAR criteria for D2T-RA with no significant differences for age (median 62 years interquartile range -IQR- 58- 65 vs. 62 IQR 60 – 63 in non-D2T), gender prevalence (23% in both groups) and positivity rates for rheumatoid factors (62% vs. 62% in non-D2T) and Anti-Citrullinated Protein Antibodies (ACPA) (69% vs. 61% in non-D2T). Conversely, D2T-RA cases had significant longer disease duration (median 15 years IQR 13–17 vs. 10 years IQR 9–11 in non-D2T; p < 0.0001). D2T-RA also had more erosions at baseline (24% vs. 11% in non-D2T; p < 0.0001) and higher disease activity index (CDAI) at the last follow up visit (15.7 ± 10.5 vs. 7.5 ± 8.8 in non-D2T; p < 0.0001). D2T-RA cases suffered with higher frequency of obesity (33% vs. 19% in non-D2T, p = 0.021) and fibromyalgia (25% vs. 10% in non-D2T, p < 0.0001). The multivariate analysis confirmed the correlations of D2T-RA with disease duration (Odds ratio -OR- 1.06, 95% confidence interval -CI—1.03–1.09; p < 0.0001), baseline erosions (OR 2.73, 95% CI 1.28–5.82; p = 0.009), obesity (OR 2.22, 95% CI 1.10–4.50; p = 0.026) and fibromyalgia (OR 3.91, 95% CI 1.76–8.70; p = 0.001), independent of age and gender. High disease activity, baseline erosions and disease duration are significantly associated with the D2T phenotype of RA while we confirm the importance of obesity and fibromyalgia.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917139","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}
Primary Sjogren’s syndrome (pSS) and autoimmune thyroiditis (AIT) share overlapping genetic and immunological profiles. This retrospective study evaluates the efficacy of machine learning algorithms, with a focus on the Random Forest Classifier, to predict the presence of thyroid-specific autoantibodies (TPOAb and TgAb) in pSS patients. A total of 96 patients with pSS were included in the retrospective study. All participants underwent a complete clinical and laboratory evaluation. All participants underwent thyroid function tests, including TPOAb and TgAb, and were accordingly divided into positive and negative thyroid autoantibody groups. Four machine learning algorithms were then used to analyze the risk factors affecting patients with pSS with positive and negative for thyroid autoantibodies. The results indicated that the Random Forest Classifier algorithm (AUC = 0.755) outperformed the other three machine learning algorithms. The random forest classifier indicated Age, IgG, C4 and dry mouth were the main factors influencing the prediction of positive thyroid autoantibodies in pSS patients. It is feasible to predict AIT in pSS using machine learning algorithms. Analyzing clinical and laboratory data from 96 pSS patients, the Random Forest model demonstrated superior performance (AUC = 0.755), identifying age, IgG levels, complement component 4 (C4), and absence of dry mouth as primary predictors. This approach offers a promising tool for early identification and management of AIT in pSS patients. This retrospective study was approved and monitored by the Ethics Committee of The Third Affiliated Hospital of Sun Yat-sen University (No.II2023-254-02).
{"title":"Predicting autoimmune thyroiditis in primary Sjogren’s syndrome patients using a random forest classifier: a retrospective study","authors":"Jia-yun Wu, Jing-yu Zhang, Wen-qi Xia, Yue-ning Kang, Ru-yi Liao, Yu-ling Chen, Xiao-min Li, Ya Wen, Fan-xuan Meng, Li-ling Xu, Sheng-hui Wen, Hui-fen Liu, Yuan-qing Li, Jie-ruo Gu, Qing Lv, Yong Ren","doi":"10.1186/s13075-024-03469-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03469-5","url":null,"abstract":"Primary Sjogren’s syndrome (pSS) and autoimmune thyroiditis (AIT) share overlapping genetic and immunological profiles. This retrospective study evaluates the efficacy of machine learning algorithms, with a focus on the Random Forest Classifier, to predict the presence of thyroid-specific autoantibodies (TPOAb and TgAb) in pSS patients. A total of 96 patients with pSS were included in the retrospective study. All participants underwent a complete clinical and laboratory evaluation. All participants underwent thyroid function tests, including TPOAb and TgAb, and were accordingly divided into positive and negative thyroid autoantibody groups. Four machine learning algorithms were then used to analyze the risk factors affecting patients with pSS with positive and negative for thyroid autoantibodies. The results indicated that the Random Forest Classifier algorithm (AUC = 0.755) outperformed the other three machine learning algorithms. The random forest classifier indicated Age, IgG, C4 and dry mouth were the main factors influencing the prediction of positive thyroid autoantibodies in pSS patients. It is feasible to predict AIT in pSS using machine learning algorithms. Analyzing clinical and laboratory data from 96 pSS patients, the Random Forest model demonstrated superior performance (AUC = 0.755), identifying age, IgG levels, complement component 4 (C4), and absence of dry mouth as primary predictors. This approach offers a promising tool for early identification and management of AIT in pSS patients. This retrospective study was approved and monitored by the Ethics Committee of The Third Affiliated Hospital of Sun Yat-sen University (No.II2023-254-02).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911487","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 : 2024-12-28DOI: 10.1186/s13075-024-03464-w
Javier Narvaez, Paola Vidal-Montal, Iván Sánchez-Rodríguez, Aida Sabaté-Llobera, Montserrat Cortés-Romera, Judith Palacios-Olid, Pol Maymó-Paituvi, Joan Miquel Nolla
To investigate differences in arterial involvement patterns on 18F-FDG PET-CT between predominant cranial and isolated extracranial phenotypes of giant cell arteritis (GCA). A retrospective review of 18F-FDG PET-CT findings was conducted on 140 patients with confirmed GCA. The patients were divided into two groups: the cranial group, which presented craniofacial ischemic symptoms either at diagnosis or during follow-up, and the isolated extracranial group which never exhibited such manifestations. Of the 140 patients (90 women), 99 (71%) were considered to have a predominantly cranial phenotype, while 41 (29%) had isolated extracranial GCA. Patients with the extracranial phenotype were younger (p = 0.001), had lower TAB positivity (25%), and experienced longer diagnostic delays (p = 0.004). Polymyalgia rheumatica was more common in the extracranial group (p = 0.029), which also showed fewer constitutional symptoms, milder increases in acute phase reactants, and more frequent limb claudication and aortic complications, although these differences were not statistically significant. When comparing arterial involvement on 18F-FDG PET-CT, we observed statistically significant differences. The extracranial phenotype showed greater involvement across all segments of the thoracic aorta (p = 0.001), as well as in the abdominal aorta (p = 0.005), subclavian (p = 0.021), iliac (p = 0.004), and femoral arteries (p = 0.025). In contrast, the cranial phenotype exhibited a higher frequency of vertebral artery involvement (p < 0.001). Significant differences in arterial involvement patterns on 18F-FDG PET-CT were observed between phenotypes. These findings may explain atypical symptoms such as inflammatory lower back pain or limb claudication and the increased risk of aortic complications in extracranial GCA.
{"title":"Comparative analysis of arterial involvement in predominant cranial and isolated extracranial phenotypes of giant cell arteritis using 18F-FDG PET-CT","authors":"Javier Narvaez, Paola Vidal-Montal, Iván Sánchez-Rodríguez, Aida Sabaté-Llobera, Montserrat Cortés-Romera, Judith Palacios-Olid, Pol Maymó-Paituvi, Joan Miquel Nolla","doi":"10.1186/s13075-024-03464-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03464-w","url":null,"abstract":"To investigate differences in arterial involvement patterns on 18F-FDG PET-CT between predominant cranial and isolated extracranial phenotypes of giant cell arteritis (GCA). A retrospective review of 18F-FDG PET-CT findings was conducted on 140 patients with confirmed GCA. The patients were divided into two groups: the cranial group, which presented craniofacial ischemic symptoms either at diagnosis or during follow-up, and the isolated extracranial group which never exhibited such manifestations. Of the 140 patients (90 women), 99 (71%) were considered to have a predominantly cranial phenotype, while 41 (29%) had isolated extracranial GCA. Patients with the extracranial phenotype were younger (p = 0.001), had lower TAB positivity (25%), and experienced longer diagnostic delays (p = 0.004). Polymyalgia rheumatica was more common in the extracranial group (p = 0.029), which also showed fewer constitutional symptoms, milder increases in acute phase reactants, and more frequent limb claudication and aortic complications, although these differences were not statistically significant. When comparing arterial involvement on 18F-FDG PET-CT, we observed statistically significant differences. The extracranial phenotype showed greater involvement across all segments of the thoracic aorta (p = 0.001), as well as in the abdominal aorta (p = 0.005), subclavian (p = 0.021), iliac (p = 0.004), and femoral arteries (p = 0.025). In contrast, the cranial phenotype exhibited a higher frequency of vertebral artery involvement (p < 0.001). Significant differences in arterial involvement patterns on 18F-FDG PET-CT were observed between phenotypes. These findings may explain atypical symptoms such as inflammatory lower back pain or limb claudication and the increased risk of aortic complications in extracranial GCA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"31 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887605","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}
Thrombocytopenia (TP) is a hematological manifestation of systemic lupus erythematosus (SLE) and is associated with unfavorable prognostic outcomes. This study aimed to develop a risk prediction model for new-onset TP in SLE patients. Based on the multicenter prospective Chinese SLE Treatment and Research Group (CSTAR) registry, newly diagnosed SLE patients without TP at registration were enrolled. The least absolute shrinkage and selection operator (LASSO) method was used for variable selection. The final model was developed using multivariate Cox regression and displayed as a nomogram. Internal validation was achieved using enhanced Bootstrap resampling. During follow-up, thrombocytopenia developed in 80 (3.52%) of 2270 lupus patients. The final risk prediction model incorporated six predictors: baseline SDI score ≥ 1 (HR 2.207, 95% CI 1.350–3.609, p = 0.002), hemolytic anemia (HR 1.953, 95% CI 1.017–3.750, p = 0.044), low complement level (HR 2.351, 95% CI 1.004–5.505, p = 0.049), positive anti-β2GPI antibody (HR 1.805, 95% CI 1.084–3.004, p = 0.024), positive Coombs test (HR 1.878, 95% CI 1.123–3.141, p = 0.017), and positive anti-histone antibody (HR 1.595, 95% CI 1.017–2.587, p = 0.059). The model’s performance was indicated by C-index values for risk prediction at one, two, and three years, which were 0.741 (0.660–0.823), 0.730 (0.655–0.805), and 0.710 (0.643–0.777), respectively; and Brier scores of 0.018 (0.012–0.024), 0.025 (0.017–0.032), and 0.037 (0.027–0.046), respectively. Calibration curves were drawn and situated near the diagonal line. This study developed the first risk prediction model for TP onset in lupus patients. Patients with baseline organ damage, hemolytic anemia, low complement, positive anti-histone antibody, positive anti-β2GPI antibody, or positive Coombs test were identified as being at high risk for thrombocytopenia and require further clinical attention.
血小板减少症（TP）是系统性红斑狼疮（SLE）的血液学表现，与不良预后相关。本研究旨在建立SLE患者新发TP的风险预测模型。基于多中心前瞻性中国SLE治疗与研究小组（CSTAR）注册表，入组新诊断的SLE患者，注册时无TP。采用最小绝对收缩和选择算子（LASSO）方法进行变量选择。最后的模型是使用多变量Cox回归建立的，并显示为nomogram。内部验证是通过增强的Bootstrap重采样实现的。随访期间，2270例狼疮患者中有80例（3.52%）出现血小板减少症。最终的风险预测模型包含6个预测因子：基线SDI评分≥1 （HR 2.207, 95% CI 1.350 ~ 3.609, p = 0.002）、溶血性贫血（HR 1.953, 95% CI 1.017 ~ 3.750, p = 0.044）、低补体水平（HR 2.351, 95% CI 1.004 ~ 5.505, p = 0.049）、抗β 2gpi抗体阳性（HR 1.805, 95% CI 1.084 ~ 3.004, p = 0.024）、Coombs试验阳性（HR 1.878, 95% CI 1.123 ~ 3.141, p = 0.017）、抗组蛋白抗体阳性（HR 1.595, 95% CI 1.017 ~ 2.587, p = 0.059）。1年、2年和3年的风险预测c指数值分别为0.741（0.66 - 0.823）、0.730（0.655-0.805）和0.710(0.643-0.777)，表明模型的性能；Brier评分分别为0.018（0.012-0.024）、0.025（0.017-0.032）和0.037（0.027-0.046）。绘制校准曲线并置于对角线附近。本研究建立了首个狼疮患者TP发病风险预测模型。基线器官损害、溶血性贫血、低补体、抗组蛋白抗体阳性、抗β 2gpi抗体阳性或Coombs试验阳性的患者被认为是血小板减少的高危人群，需要进一步的临床关注。
{"title":"Risk prediction of new-onset thrombocytopenia in patients with systemic lupus erythematosus: a multicenter prospective cohort study based on Chinese SLE treatment and research group (CSTAR) registry","authors":"Yupei Zhang, Nan Jiang, Xinwang Duan, Jian Xu, Lijun Wu, Wei Wei, Weiguo Xiao, Li Luo, Zhenyu Jiang, Yanhong Wang, Jiuliang Zhao, Qian Wang, Xinping Tian, Mengtao Li, Xiaofeng Zeng","doi":"10.1186/s13075-024-03460-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03460-0","url":null,"abstract":"Thrombocytopenia (TP) is a hematological manifestation of systemic lupus erythematosus (SLE) and is associated with unfavorable prognostic outcomes. This study aimed to develop a risk prediction model for new-onset TP in SLE patients. Based on the multicenter prospective Chinese SLE Treatment and Research Group (CSTAR) registry, newly diagnosed SLE patients without TP at registration were enrolled. The least absolute shrinkage and selection operator (LASSO) method was used for variable selection. The final model was developed using multivariate Cox regression and displayed as a nomogram. Internal validation was achieved using enhanced Bootstrap resampling. During follow-up, thrombocytopenia developed in 80 (3.52%) of 2270 lupus patients. The final risk prediction model incorporated six predictors: baseline SDI score ≥ 1 (HR 2.207, 95% CI 1.350–3.609, p = 0.002), hemolytic anemia (HR 1.953, 95% CI 1.017–3.750, p = 0.044), low complement level (HR 2.351, 95% CI 1.004–5.505, p = 0.049), positive anti-β2GPI antibody (HR 1.805, 95% CI 1.084–3.004, p = 0.024), positive Coombs test (HR 1.878, 95% CI 1.123–3.141, p = 0.017), and positive anti-histone antibody (HR 1.595, 95% CI 1.017–2.587, p = 0.059). The model’s performance was indicated by C-index values for risk prediction at one, two, and three years, which were 0.741 (0.660–0.823), 0.730 (0.655–0.805), and 0.710 (0.643–0.777), respectively; and Brier scores of 0.018 (0.012–0.024), 0.025 (0.017–0.032), and 0.037 (0.027–0.046), respectively. Calibration curves were drawn and situated near the diagonal line. This study developed the first risk prediction model for TP onset in lupus patients. Patients with baseline organ damage, hemolytic anemia, low complement, positive anti-histone antibody, positive anti-β2GPI antibody, or positive Coombs test were identified as being at high risk for thrombocytopenia and require further clinical attention.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887606","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 : 2024-12-23DOI: 10.1186/s13075-024-03463-x
M. Aronsson, S. Bergman, E. Lindqvist, M. L. E. Andersson
High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in blood and CWP in patients with RA. In this cross-sectional study 334 patients with RA filled in a questionnaire including a pain mannequin and questions on weight, length and waist circumference. Data from the pain mannequin was used to calculate CWP. The subjects also submitted blood samples to a biobank that were used for this study to determine leptin levels using an ELISA-method. Patients fulfilling the 2019 criteria for CWP in this study had significantly higher leptin levels, waist circumferences and BMI. There was a significant association between leptin levels and CWP, odds ratio (OR) 1.014 (95% confidence interval (CI) 1.007–1.020), p < 0.001. The association remained after adjusting for BMI, gender and age OR 1.008 (95% CI 1.000-1.017), p 0.046. When leptin was divided into quartile groups a trend could be observed where higher leptin values gave higher OR for CWP. This study showed an increased occurrence of CWP in RA-patients with high leptin levels. The association between leptin and CWP remained after adjusting for gender, age and BMI or waist circumference. This suggests that not just production of leptin in the adipose tissue, but also other factors such as leptin resistance may play a role. The association between leptin and CWP was strongest in the patients with the highest leptin levels. This study is a cross-sectional study without intervention and the cohort used was initiated prior to the implementation of mandatory registration requirements, therefore it is not registered.
高身体质量指数（BMI）已被证明与慢性广泛性疼痛（CWP）有关，无论是在类风湿关节炎（RA）还是其他疼痛状况，如纤维肌痛。对脂肪组织及其脂肪因子的研究正在兴起，比如描述得很好的瘦素。本研究的目的是确定RA患者血液中瘦素水平与CWP之间是否存在关联。在这项横断面研究中，334名RA患者填写了一份调查问卷，包括一个疼痛模型和关于体重、身高和腰围的问题。疼痛模型数据用于计算CWP。受试者还将血液样本提交给生物库，用于本研究使用elisa法测定瘦素水平。在本研究中，符合2019年CWP标准的患者瘦素水平、腰围和BMI均明显较高。瘦素水平与CWP之间存在显著相关性，比值比（OR）为1.014(95%可信区间（CI）为1.007 ~ 1.020),p < 0.001。在调整BMI、性别和年龄后，相关性仍为1.008 (95% CI 1.000-1.017), p 0.046。当瘦素被分成四分位数组时，可以观察到一个趋势，即瘦素值越高，CWP的OR越高。该研究显示，高瘦素水平的ra患者CWP发生率增加。在调整性别、年龄、BMI或腰围后，瘦素和CWP之间的关系仍然存在。这表明，不仅仅是脂肪组织中瘦素的产生，瘦素抵抗等其他因素也可能起作用。在瘦素水平最高的患者中，瘦素与CWP之间的相关性最强。本研究是一项无干预的横断面研究，所使用的队列是在实施强制性注册要求之前启动的，因此未进行注册。
{"title":"High leptin levels in blood are associated with chronic widespread pain in rheumatoid arthritis","authors":"M. Aronsson, S. Bergman, E. Lindqvist, M. L. E. Andersson","doi":"10.1186/s13075-024-03463-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03463-x","url":null,"abstract":"High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in blood and CWP in patients with RA. In this cross-sectional study 334 patients with RA filled in a questionnaire including a pain mannequin and questions on weight, length and waist circumference. Data from the pain mannequin was used to calculate CWP. The subjects also submitted blood samples to a biobank that were used for this study to determine leptin levels using an ELISA-method. Patients fulfilling the 2019 criteria for CWP in this study had significantly higher leptin levels, waist circumferences and BMI. There was a significant association between leptin levels and CWP, odds ratio (OR) 1.014 (95% confidence interval (CI) 1.007–1.020), p < 0.001. The association remained after adjusting for BMI, gender and age OR 1.008 (95% CI 1.000-1.017), p 0.046. When leptin was divided into quartile groups a trend could be observed where higher leptin values gave higher OR for CWP. This study showed an increased occurrence of CWP in RA-patients with high leptin levels. The association between leptin and CWP remained after adjusting for gender, age and BMI or waist circumference. This suggests that not just production of leptin in the adipose tissue, but also other factors such as leptin resistance may play a role. The association between leptin and CWP was strongest in the patients with the highest leptin levels. This study is a cross-sectional study without intervention and the cohort used was initiated prior to the implementation of mandatory registration requirements, therefore it is not registered.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873905","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}
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Diet is recognized as a modifiable factor that may influence inflammation and potentially accelerate RA progression. Nevertheless, the effects of diverse dietary patterns and their combined impact on RA progression and long-term mortality remain inadequately understood. This study examined the association between dietary patterns and mortality in patients with RA, focusing on the Healthy Eating Index (HEI-2015) and Dietary Inflammatory Index (DII) and evaluating their combined effects. The analysis included 2,069 patients with RA from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2018. Weighted multi-variable Cox regression models estimated the relationship between the DII, HEI-2015, combined dietary patterns, and all-cause mortality in patients with RA. Linear associations between the DII, HEI-2015, and all-cause mortality were analyzed using restricted cubic splines (RCS). Dietary factors associated with mortality were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) method, and subgroup and sensitivity analyses were conducted to strengthen the findings. Participants had a median age of 59 years (IQR: 48–69), with 42.1% male. Adjusting for potential confounders, the hazard ratio (HR) for individuals adhering to healthy and anti-inflammatory dietary patterns, as opposed to unhealthy and pro-inflammatory patterns, was 0.70 (95% CI: 0.53–0.92; adjusted P = 0.01; trend P = 0.02). In weighted Cox analyses of the DII and HEI-2015, higher quartiles showed no significant mortality risk difference from the lowest quartiles. The LASSO-Cox model identified 12 dietary components predictive of all-cause mortality in patients with RA, with an AUC of 0.749 (0.682–0.815) at 1 year, 0.763 (0.724–0.802) at 3 years, 0.783 (0.749–0.802) at 5 years, and 0.868 (0.712–0.938) for all death events. Kaplan-Meier analysis revealed that the low-risk dietary group exhibited significantly lower mortality compared to the high-risk group (P < 0.001). These findings suggest that combining a higher HEI-2015 with a lower DII score correlates with reduced all-cause mortality risk among patients with RA, supporting dietary modification as a potential strategy to prevent premature death in this population.
{"title":"The comprehensive relationship between combined anti-inflammatory and healthy diets and all-cause mortality in rheumatoid arthritis: results from NHANES 2003–2018","authors":"Penghe Wang, Dongni Wang, Jiayu Sui, Shuang Liu, Yingjing Kong, Hongwei Lei, Maomao Zhang","doi":"10.1186/s13075-024-03462-y","DOIUrl":"https://doi.org/10.1186/s13075-024-03462-y","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Diet is recognized as a modifiable factor that may influence inflammation and potentially accelerate RA progression. Nevertheless, the effects of diverse dietary patterns and their combined impact on RA progression and long-term mortality remain inadequately understood. This study examined the association between dietary patterns and mortality in patients with RA, focusing on the Healthy Eating Index (HEI-2015) and Dietary Inflammatory Index (DII) and evaluating their combined effects. The analysis included 2,069 patients with RA from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2018. Weighted multi-variable Cox regression models estimated the relationship between the DII, HEI-2015, combined dietary patterns, and all-cause mortality in patients with RA. Linear associations between the DII, HEI-2015, and all-cause mortality were analyzed using restricted cubic splines (RCS). Dietary factors associated with mortality were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) method, and subgroup and sensitivity analyses were conducted to strengthen the findings. Participants had a median age of 59 years (IQR: 48–69), with 42.1% male. Adjusting for potential confounders, the hazard ratio (HR) for individuals adhering to healthy and anti-inflammatory dietary patterns, as opposed to unhealthy and pro-inflammatory patterns, was 0.70 (95% CI: 0.53–0.92; adjusted P = 0.01; trend P = 0.02). In weighted Cox analyses of the DII and HEI-2015, higher quartiles showed no significant mortality risk difference from the lowest quartiles. The LASSO-Cox model identified 12 dietary components predictive of all-cause mortality in patients with RA, with an AUC of 0.749 (0.682–0.815) at 1 year, 0.763 (0.724–0.802) at 3 years, 0.783 (0.749–0.802) at 5 years, and 0.868 (0.712–0.938) for all death events. Kaplan-Meier analysis revealed that the low-risk dietary group exhibited significantly lower mortality compared to the high-risk group (P < 0.001). These findings suggest that combining a higher HEI-2015 with a lower DII score correlates with reduced all-cause mortality risk among patients with RA, supporting dietary modification as a potential strategy to prevent premature death in this population. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873827","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 : 2024-12-23DOI: 10.1186/s13075-024-03429-z
Prachi Agnihotri, Mohd Saquib, Lovely Joshi, Swati Malik, Debolina Chakraborty, Ashish Sarkar, Uma Kumar, Sagarika Biswas
Rheumatoid arthritis (RA) is a chronic inflammatory condition that, despite available approaches to manage the disease, lacks an efficient treatment and timely diagnosis. Using the most advanced omics technique, metabolomics and proteomics approach, we explored varied metabolites and proteins to identify unique metabolite-protein signatures involved in the disease pathogenesis of RA. Untargeted metabolomics (n = 20) and proteomics (n = 60) of RA patients’ plasma were carried out by HPLC/LC-MS/MS and SWATH, respectively and analyzed by Metaboanalyst. The targets of metabolite retrieved by PharmMapper were matched with SWATH data, and joint pathway analysis was carried out. An in-vitro study of metabolites in TNF-α induced SW982 cells was conducted by Western, RT-PCR, scratch, and ROS scavenging assay. The effect of GUDCA was also evaluated in the CIA rat model. A Total of 82 metabolites and 231 differential proteins were revealed. Porphyrin and chlorophyll pathway and its metabolite Glycoursodeoxycholic acid (GUDCA) was found to be significantly altered. In vitro analysis has shown that GUDCA reduces inflammation thus offering protection against ROS production and cell proliferation. PharmMapper analysis revealed that GUDCA was significantly linked with identified SWATH proteins insulin like growth factor-1(IGF1), and Transthyretin (TTR) and it upregulates the expression of IGF1 and downregulates the expression of TTR in both in vitro and in vivo models. GUDCA was found to possess antioxidative, antiproliferative properties and an effective anti-inflammatory property at a low dosage. It may be considered as a potential therapeutic option for reducing the inflammatory parameters associated with RA.
类风湿性关节炎（RA）是一种慢性炎症，尽管有治疗方法，但缺乏有效的治疗和及时的诊断。利用最先进的组学技术，代谢组学和蛋白质组学方法，我们探索了各种代谢物和蛋白质，以确定参与RA疾病发病机制的独特代谢物-蛋白质特征。采用HPLC/LC-MS/MS和SWATH分别对RA患者血浆进行非靶向代谢组学（n = 20）和蛋白质组学（n = 60），并采用Metaboanalyst进行分析。将PharmMapper检索到的代谢物靶点与SWATH数据进行匹配，并进行联合通路分析。采用Western、RT-PCR、scratch和ROS清除实验对TNF-α诱导的SW982细胞代谢产物进行体外研究。在CIA大鼠模型中评价GUDCA的作用。共发现82种代谢物和231种差异蛋白。卟啉和叶绿素途径及其代谢物甘氨酸脱氧胆酸（GUDCA）发生了显著改变。体外分析表明，GUDCA可以减少炎症，从而提供抗ROS产生和细胞增殖的保护。PharmMapper分析显示，GUDCA与SWATH蛋白胰岛素样生长因子-1（insulin like growth factor-1, IGF1）和转甲状腺素（Transthyretin， TTR）显著相关，在体外和体内模型中上调IGF1的表达，下调TTR的表达。发现GUDCA在低剂量下具有抗氧化、抗增殖和有效的抗炎特性。它可能被认为是一种潜在的治疗选择，以减少与RA相关的炎症参数。
{"title":"Integrative metabolomic-proteomic analysis uncovers a new therapeutic approach in targeting rheumatoid arthritis","authors":"Prachi Agnihotri, Mohd Saquib, Lovely Joshi, Swati Malik, Debolina Chakraborty, Ashish Sarkar, Uma Kumar, Sagarika Biswas","doi":"10.1186/s13075-024-03429-z","DOIUrl":"https://doi.org/10.1186/s13075-024-03429-z","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic inflammatory condition that, despite available approaches to manage the disease, lacks an efficient treatment and timely diagnosis. Using the most advanced omics technique, metabolomics and proteomics approach, we explored varied metabolites and proteins to identify unique metabolite-protein signatures involved in the disease pathogenesis of RA. Untargeted metabolomics (n = 20) and proteomics (n = 60) of RA patients’ plasma were carried out by HPLC/LC-MS/MS and SWATH, respectively and analyzed by Metaboanalyst. The targets of metabolite retrieved by PharmMapper were matched with SWATH data, and joint pathway analysis was carried out. An in-vitro study of metabolites in TNF-α induced SW982 cells was conducted by Western, RT-PCR, scratch, and ROS scavenging assay. The effect of GUDCA was also evaluated in the CIA rat model. A Total of 82 metabolites and 231 differential proteins were revealed. Porphyrin and chlorophyll pathway and its metabolite Glycoursodeoxycholic acid (GUDCA) was found to be significantly altered. In vitro analysis has shown that GUDCA reduces inflammation thus offering protection against ROS production and cell proliferation. PharmMapper analysis revealed that GUDCA was significantly linked with identified SWATH proteins insulin like growth factor-1(IGF1), and Transthyretin (TTR) and it upregulates the expression of IGF1 and downregulates the expression of TTR in both in vitro and in vivo models. GUDCA was found to possess antioxidative, antiproliferative properties and an effective anti-inflammatory property at a low dosage. It may be considered as a potential therapeutic option for reducing the inflammatory parameters associated with RA. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"64 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874054","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}
To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL_RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP. This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL_RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks. The mean age of subjects was 59.8 years (range: 24, 86) and the mean BMI was 27.76 kg/m2 (range: 17.5, 52.0). Incidence of ADA after dosing was low in both groups: 1.4% in DRL_RI group on Day 15, Week 8, and Week 12; and 2.9% in RP/RMP group at Week 12. Only 1 patient in DRL_RI group was positive for NAbs at Week 8. ADA titre values did not significantly differ between the two groups. The time-matched rituximab concentration was comparable between groups, indicating no interference for immunogenicity assessment. Treatment-emergent adverse events (TEAEs) were reported by 34.3% and 38.6% patients, respectively, in DRL_RI and RP/RMP groups. Incidences of TEAEs that were drug-related, leading to treatment discontinuation, grade ≥ 3, or serious, were also comparable. Immunogenicity was low and comparable in RA patients transitioning to DRL_RI or continuing on RP/RMP. The overall safety profile in patients transitioning to DRL_RI did not appear to differ in frequency, severity, or quality from patients continuing on RP/RMP and was in line with the known safety profile of rituximab. ClinicalTrials.gov identifier NCT0426877 EudraCT:2019-002810-37 US IND 112766. • Immunogenicity and safety in patients with active RA transitioning from reference rituximab to DRL_RI (biosimilar rituximab) were comparable to those continuing with reference rituximab. • Incidence of ADA after dosing was low and similar between patients transitioning to DRL_RI vs. continuing with reference rituximab. • Adverse events in patients who transitioned to DRL_RI or continuing treatment with the reference rituximab were comparable, and overall, in line with the known safety profile of rituximab.
评估活动性类风湿关节炎（RA）患者从美罗华过渡的免疫原性和安全性[美罗华：参考产品（RP）；欧盟批准的利妥昔单抗：参考药物（RMP）]到DRL_RI（拟议的利妥昔单抗生物仿制药），与继续使用RP/RMP的药物进行比较。这项双盲、随机、3期研究纳入了140名RA患者，他们之前曾暴露于RP/RMP；过渡到DRL_RI （n = 70）或继续RP/RMP (n = 70)，在第1天和第15天两次1000 mg输注。评估包括12周时间匹配利妥昔单抗浓度（TMRC）、抗药物抗体（ADAs）、中和抗体（nab）和ADA滴度，以及安全随访至26周。受试者平均年龄为59.8岁（范围：24、86），平均BMI为27.76 kg/m2（范围：17.5、52.0）。两组给药后ADA的发生率均较低：DRL_RI组在第15天、第8周和第12周的发生率为1.4%；第12周，RP/RMP组为2.9%。DRL_RI组只有1例患者在第8周nab阳性。两组间ADA滴度值无显著差异。时间匹配的利妥昔单抗浓度在两组之间具有可比性，表明对免疫原性评估没有干扰。DRL_RI组和RP/RMP组出现治疗不良事件（teae）的比例分别为34.3%和38.6%。与药物相关、导致停药、≥3级或严重teae的发生率也具有可比性。在过渡到DRL_RI或继续RP/RMP的RA患者中，免疫原性较低且相当。过渡到DRL_RI的患者的总体安全性与继续使用RP/RMP的患者在频率、严重程度或质量上没有差异，并且与利妥昔单抗的已知安全性一致。ClinicalTrials.gov编号NCT0426877稿号：2019-002810-37 US IND 112766。•活动性RA患者从参考利妥昔单抗过渡到DRL_RI（生物仿制药利妥昔单抗）的免疫原性和安全性与继续使用参考利妥昔单抗的患者相当。•在过渡到DRL_RI和继续使用利妥昔单抗的患者中，给药后ADA的发生率较低且相似。•过渡到DRL_RI或继续使用参考利妥昔单抗治疗的患者的不良事件具有可比性，总体而言，符合利妥昔单抗已知的安全性。
{"title":"Comparing immunogenicity and safety following transition from reference rituximab to biosimilar rituximab (DRL_RI) in patients with rheumatoid arthritis: a randomized, double-blind, phase 3 study","authors":"Narendra Maharaj, Dharma Rao Uppada, Naveen Reddy, Pramod Reddy, Anastas Batalov, Delina lvanova, Nedyalka Staykova, Asta Baranauskaite, Laila Amirali Hassan","doi":"10.1186/s13075-024-03456-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03456-w","url":null,"abstract":"To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL_RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP. This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL_RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks. The mean age of subjects was 59.8 years (range: 24, 86) and the mean BMI was 27.76 kg/m2 (range: 17.5, 52.0). Incidence of ADA after dosing was low in both groups: 1.4% in DRL_RI group on Day 15, Week 8, and Week 12; and 2.9% in RP/RMP group at Week 12. Only 1 patient in DRL_RI group was positive for NAbs at Week 8. ADA titre values did not significantly differ between the two groups. The time-matched rituximab concentration was comparable between groups, indicating no interference for immunogenicity assessment. Treatment-emergent adverse events (TEAEs) were reported by 34.3% and 38.6% patients, respectively, in DRL_RI and RP/RMP groups. Incidences of TEAEs that were drug-related, leading to treatment discontinuation, grade ≥ 3, or serious, were also comparable. Immunogenicity was low and comparable in RA patients transitioning to DRL_RI or continuing on RP/RMP. The overall safety profile in patients transitioning to DRL_RI did not appear to differ in frequency, severity, or quality from patients continuing on RP/RMP and was in line with the known safety profile of rituximab. ClinicalTrials.gov identifier NCT0426877 EudraCT:2019-002810-37 US IND 112766. • Immunogenicity and safety in patients with active RA transitioning from reference rituximab to DRL_RI (biosimilar rituximab) were comparable to those continuing with reference rituximab. • Incidence of ADA after dosing was low and similar between patients transitioning to DRL_RI vs. continuing with reference rituximab. • Adverse events in patients who transitioned to DRL_RI or continuing treatment with the reference rituximab were comparable, and overall, in line with the known safety profile of rituximab.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"113 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867035","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 : 2024-12-20DOI: 10.1186/s13075-024-03457-9
Terese Geraghty, Shingo Ishihara, Alia M. Obeidat, Natalie S. Adamczyk, Rahel S. Hunter, Jun Li, Lai Wang, Hoomin Lee, Frank C. Ko, Anne-Marie Malfait, Rachel E. Miller
Osteoarthritis (OA) is a painful degenerative joint disease and a leading source of years lived with disability globally due to inadequate treatment options. Neuroimmune interactions reportedly contribute to OA pain pathogenesis. Notably, in rodents, macrophages in the DRG are associated with onset of persistent OA pain. Our objective was to determine the effects of acute systemic macrophage depletion on pain-related behaviors and joint damage using surgical mouse models in both sexes. We depleted CSF1R + macrophages by treating male macrophage Fas-induced apoptosis (MaFIA) transgenic mice 8- or 16-weeks post destabilization of the medial meniscus (DMM) with AP20187 or vehicle control (10 mg/kg i.p., 1x/day for 5 days), or treating female MaFIA mice 12 weeks post partial meniscectomy (PMX) with AP20187 or vehicle control. We measured pain-related behaviors 1–3 days before and after depletion, and, 3–4 days after the last injection we examined joint histopathology and performed flow cytometry of the dorsal root ganglia (DRGs). In a separate cohort of male 8-week DMM mice or age-matched naïve vehicle controls, we conducted DRG bulk RNA-sequencing analyses after the 5-day vehicle or AP20187 treatment. Eight- and 16-weeks post DMM in male mice, AP20187-induced macrophage depletion resulted in attenuated mechanical allodynia and knee hyperalgesia. Female mice showed alleviation of mechanical allodynia, knee hyperalgesia, and weight bearing deficits after macrophage depletion at 12 weeks post PMX. Macrophage depletion did not affect the degree of cartilage degeneration, osteophyte width, or synovitis in either sex. Flow cytometry of the DRG revealed that macrophages and neutrophils were reduced after AP20187 treatment. In addition, in the DRG, only MHCII + M1-like macrophages were significantly decreased, while CD163 + MHCII- M2-like macrophages were not affected in both sexes. DRG bulk RNA-seq revealed that Cxcl10 and Il1b were upregulated with DMM surgery compared to naïve mice, and downregulated in DMM after acute macrophage depletion. Acute systemic macrophage depletion reduced the levels of pro-inflammatory macrophages in the DRG and alleviated pain-related behaviors in established surgically induced OA in mice of both sexes, without affecting joint damage. Overall, these studies provide insight into immune cell regulation in the DRG during OA.
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