Pub Date : 2024-09-14DOI: 10.1186/s13075-024-03395-6
Daniel P. Joyce, Jeffrey S. Berger, Allison Guttmann, Ghadeer Hasan, Jill P. Buyon, H. Michael Belmont, Jane Salmon, Anca Askanase, Joan Bathon, Laura Geraldino-Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Kamil E. Barbour, Heather T. Gold, Hilary Parton, Peter M. Izmirly
The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) and the 2013–2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2–2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7–3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1–15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2–4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2–6.5) among patients aged 20–49 years and 2.2 (95%CI:2.1–2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5–12.1), Hispanic/Latino (10.9, 95%CI:10.5–11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20–49 had the highest CVE prevalence ratios. These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.
{"title":"Prevalence of cardiovascular events in a population-based registry of patients with systemic lupus erythematosus","authors":"Daniel P. Joyce, Jeffrey S. Berger, Allison Guttmann, Ghadeer Hasan, Jill P. Buyon, H. Michael Belmont, Jane Salmon, Anca Askanase, Joan Bathon, Laura Geraldino-Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Kamil E. Barbour, Heather T. Gold, Hilary Parton, Peter M. Izmirly","doi":"10.1186/s13075-024-03395-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03395-6","url":null,"abstract":"The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) and the 2013–2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2–2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7–3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1–15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2–4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2–6.5) among patients aged 20–49 years and 2.2 (95%CI:2.1–2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5–12.1), Hispanic/Latino (10.9, 95%CI:10.5–11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20–49 had the highest CVE prevalence ratios. These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231457","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 : 2024-09-11DOI: 10.1186/s13075-024-03387-6
Hongxia Yang, Chao Sun, Lifang Ye, Yuetong Xu, Sang Lin, Qinglin Peng, Guochun Wang, Xin Lu
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician’s Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis. • Anti-HMGCR IgM-positive patients had a younger age of onset and more neck weakness than anti-HMGCR IgM-negative patients. • The levels of anti-HMGCR IgG and IgM are associated with disease activity in anti-HMGCR-positive patients. • Anti-HMGCR IgM is associated with refractory outcome and poor prognosis.
{"title":"Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy","authors":"Hongxia Yang, Chao Sun, Lifang Ye, Yuetong Xu, Sang Lin, Qinglin Peng, Guochun Wang, Xin Lu","doi":"10.1186/s13075-024-03387-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03387-6","url":null,"abstract":"Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician’s Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis. • Anti-HMGCR IgM-positive patients had a younger age of onset and more neck weakness than anti-HMGCR IgM-negative patients. • The levels of anti-HMGCR IgG and IgM are associated with disease activity in anti-HMGCR-positive patients. • Anti-HMGCR IgM is associated with refractory outcome and poor prognosis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166285","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}
Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.
系统性红斑狼疮（SLE）是典型的自身免疫性疾病，其特点是 CD4+ T 细胞活性亢进，继而引发狼疮病理变化。滤泡辅助 T（TFH）细胞在 B 细胞成熟和抗体产生过程中发挥着重要作用。然而，究竟是哪个特定的cTFH细胞亚群驱动了B细胞功能，并促成了抗dsDNA抗体的产生和系统性红斑狼疮的发病机制，目前仍不清楚。研究人员使用非活动性（11 人）和活动性（21 人）系统性红斑狼疮患者的外周血单核细胞来确定和检测循环 TFH 细胞（cTFH）、记忆 cTFH 和 B 细胞亚群的频率和表型。分析了 cTFH 细胞亚群和表型、B 细胞亚群、抗dsDNA 自身抗体和临床参数之间的相关性。在活动性系统性红斑狼疮患者中，cTFH1和cTFH17细胞明显扩增和活化。这些扩增的cTFH细胞表现出记忆表型；cTFH1细胞主要是中心记忆（CM）型，而cTFH17细胞主要是效应记忆（EM）型。这些患者的 B 细胞亚群表型显示，aNAV 和 DN2 B 细胞的频率增加。临床发现，ICOS+ cTFH1、ICOS+ cTFH17 细胞与 SLEDAI-2k 评分相关。对cTFH-B细胞关系的分析表明，ICOS+ cTFH1细胞、aNAV B细胞和抗dsDNA抗体之间存在正相关。ICOS+ cTFH17细胞的激活与aNAV和DN2 B细胞的扩增明显相关。cTFH1和cTFH17亚群中CM细胞的存在与aNAV和DN2 B细胞频率相关。研究发现，系统性红斑狼疮 cTFH 细胞向 cTFH1 和 cTFH17 细胞极化；这些 cTFH 亚群的激活与疾病活动评分、aNAV、DN2 B 细胞扩增和抗dsDNA 抗体水平显著相关。因此，cTFH1、cTFH17 和 B 细胞之间的相互作用可能有助于自身抗体的形成和系统性红斑狼疮的发病机制。
{"title":"Activation of circulating TFH17 cells associated with activated naive and double negative 2 B cell expansion, and disease activity in systemic lupus erythematosus patients","authors":"Tipanan Khunsri, Pongsakorn Thawornpan, Pachara Tianpothong, Thanitta Suangtamai, Pintip Ngamjanyaporn, Chaniya Leepiyasakulchai, Kittikorn Wangriatisak, Prapaporn Pisitkun, Patchanee Chootong","doi":"10.1186/s13075-024-03394-7","DOIUrl":"https://doi.org/10.1186/s13075-024-03394-7","url":null,"abstract":"Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166283","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}
Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48). In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. NCT03830203 and EudraCT 2018-002202-31.
{"title":"A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)","authors":"Xiaomei Leng, Piotr Leszczyński, Slawomir Jeka, Shengyun Liu, Huaxiang Liu, Malgorzata Miakisz, Jieruo Gu, Lali Kilasonia, Mykola Stanislavchuk, Xiaolei Yang, Yinbo Zhou, Qingfeng Dong, Marian Mitroiu, Janet Addison, Mourad F. Rezk, Xiaofeng Zeng","doi":"10.1186/s13075-024-03375-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03375-w","url":null,"abstract":"Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48). In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. NCT03830203 and EudraCT 2018-002202-31.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144343","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}
Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.
{"title":"Factors related to elevated serum immunoglobulin G4 (IgG4) levels in a Japanese general population","authors":"Shunsuke Tsuge, Hiroshi Fujii, Mami Tamai, Hiromasa Tsujiguchi, Misaki Yoshida, Nobuhiro Suzuki, Yoshinori Takahashi, Akari Takeji, Shigeto Horita, Yuhei Fujisawa, Takahiro Matsunaga, Takeshi Zoshima, Ryo Nishioka, Hiromi Nuka, Satoshi Hara, Yukiko Tani, Yasunori Suzuki, Kiyoaki Ito, Kazunori Yamada, Satoshi Nakazaki, Akinori Hara, Atsushi Kawakami, Hiroyuki Nakamura, Ichiro Mizushima, Yasunori Iwata, Mitsuhiro Kawano","doi":"10.1186/s13075-024-03391-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03391-w","url":null,"abstract":"Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142432","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 : 2024-09-04DOI: 10.1186/s13075-024-03386-7
Imke Redeker, Stefan Moustakis, Styliani Tsiami, Xenofon Baraliakos, David Kiefer, Ioana Andreica, Björn Buehring, Jürgen Braun, Uta Kiltz
To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.
{"title":"A Bayesian model to analyse the association of comorbidities with biosimilar treatment retention in a non-medical switch scenario in patients with inflammatory rheumatic musculoskeletal diseases","authors":"Imke Redeker, Stefan Moustakis, Styliani Tsiami, Xenofon Baraliakos, David Kiefer, Ioana Andreica, Björn Buehring, Jürgen Braun, Uta Kiltz","doi":"10.1186/s13075-024-03386-7","DOIUrl":"https://doi.org/10.1186/s13075-024-03386-7","url":null,"abstract":"To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130731","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 : 2024-08-31DOI: 10.1186/s13075-024-03385-8
Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Gabriel Vega Cornejo, Jordi Antón, Ruben Cuttica, Michael Henrickson, Ivan Foeldvari, Daniel J Kingsbury, Margarita Askelson, Jinqi Liu, Sumanta Mukherjee, Robert L Wong, Daniel J Lovell, Alberto Martini, Nicolino Ruperto, Alexei A Grom
<p><b>Correction: Arthritis Res Ther 26</b>,<b> 125 (2024)</b></p><p><b>https://doi.org/10.1186/s13075-024-03347-0</b></p><p>Following publication of the original article [1], the authors reported an error to Supplementary Material 2. Supplementary Material 2 was removed as the file was only for the reviewers’ reference and not meant to be published.</p><p>The original article [1] has been updated.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Brunner HI, Schulert GS, Sproles A, et al. S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis. Arthritis Res Ther. 2024;26:125. https://doi.org/10.1186/s13075-024-03347-0.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Division of Rheumatology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA</p><p>Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Michael Henrickson, Daniel J Lovell & Alexei A Grom</p></li><li><p>Hospital México Americano, Guadalajara, CREA, Mexico</p><p>Gabriel Vega Cornejo</p></li><li><p>Pediatric Rheumatology Department, Hospital Sant Joan de Deu, Universitat de Barcelona, Barcelona, Spain</p><p>Jordi Antón</p></li><li><p>Ruben Cuttica MD, Pediatric Rheumatology, Hospital General de Ninos Pedro de Elizalde, Buenos Aires, Argentina</p><p>Ruben Cuttica</p></li><li><p>Hamburg Centre for Pediatric and Adolescent Rheumatology, Schon Klinik Hamburg Eilbek, Hamburg, Germany</p><p>Ivan Foeldvari</p></li><li><p>Division of Rheumatology, Randall Children’s Hospital at Legacy Emanuel, Portland, OR, USA</p><p>Daniel J Kingsbury</p></li><li><p>Global Biometric Sciences, Bristol Myers Squibb, Princeton, NJ, USA</p><p>Margarita Askelson</p></li><li><p>Translational Medicine, Bristol Myers Squibb, Princeton, NJ, USA</p><p>Jinqi Liu & Sumanta Mukherjee</p></li><li><p>Bristol Myers Squibb, Immunology and Fibrosis, Princeton, NJ, USA</p><p>Robert L Wong</p></li><li><p>Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Universita degli Studi di Genova, Genoa, Italy</p><p>Alberto Martini</p></li><li><p>IRCCS Istituto Giannina Gaslini, Gaslini Trial Centre/Servizio di Sperimentazioni Cliniche Pediatriche, PRINTO, Genoa, Italy</p><p>Nicolino Ruperto</p></li></ol><span>Authors</span><ol><li><span>Hermine I Brunner</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Grant S Schulert</span>View author publications<p>You can also search for this author in <span>PubM
如果文章的知识共享许可协议中没有包含相关材料，而您的使用意图又未得到法律法规的允许或超出了允许的使用范围，您需要直接从版权所有者处获得许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明，否则创作共用公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Brunner, H.I., Schulert, G.S., Sproles, A. et al. Correction：S100蛋白作为多关节幼年特发性关节炎阿巴他赛普反应的潜在预测性生物标志物。Arthritis Res Ther 26, 154 (2024). https://doi.org/10.1186/s13075-024-03385-8Download citationPublished: 31 August 2024DOI: https://doi.org/10.1186/s13075-024-03385-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Correction: S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis","authors":"Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Gabriel Vega Cornejo, Jordi Antón, Ruben Cuttica, Michael Henrickson, Ivan Foeldvari, Daniel J Kingsbury, Margarita Askelson, Jinqi Liu, Sumanta Mukherjee, Robert L Wong, Daniel J Lovell, Alberto Martini, Nicolino Ruperto, Alexei A Grom","doi":"10.1186/s13075-024-03385-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03385-8","url":null,"abstract":"<p><b>Correction: Arthritis Res Ther 26</b>,<b> 125 (2024)</b></p><p><b>https://doi.org/10.1186/s13075-024-03347-0</b></p><p>Following publication of the original article [1], the authors reported an error to Supplementary Material 2. Supplementary Material 2 was removed as the file was only for the reviewers’ reference and not meant to be published.</p><p>The original article [1] has been updated.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Brunner HI, Schulert GS, Sproles A, et al. S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis. Arthritis Res Ther. 2024;26:125. https://doi.org/10.1186/s13075-024-03347-0.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Division of Rheumatology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA</p><p>Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Michael Henrickson, Daniel J Lovell & Alexei A Grom</p></li><li><p>Hospital México Americano, Guadalajara, CREA, Mexico</p><p>Gabriel Vega Cornejo</p></li><li><p>Pediatric Rheumatology Department, Hospital Sant Joan de Deu, Universitat de Barcelona, Barcelona, Spain</p><p>Jordi Antón</p></li><li><p>Ruben Cuttica MD, Pediatric Rheumatology, Hospital General de Ninos Pedro de Elizalde, Buenos Aires, Argentina</p><p>Ruben Cuttica</p></li><li><p>Hamburg Centre for Pediatric and Adolescent Rheumatology, Schon Klinik Hamburg Eilbek, Hamburg, Germany</p><p>Ivan Foeldvari</p></li><li><p>Division of Rheumatology, Randall Children’s Hospital at Legacy Emanuel, Portland, OR, USA</p><p>Daniel J Kingsbury</p></li><li><p>Global Biometric Sciences, Bristol Myers Squibb, Princeton, NJ, USA</p><p>Margarita Askelson</p></li><li><p>Translational Medicine, Bristol Myers Squibb, Princeton, NJ, USA</p><p>Jinqi Liu & Sumanta Mukherjee</p></li><li><p>Bristol Myers Squibb, Immunology and Fibrosis, Princeton, NJ, USA</p><p>Robert L Wong</p></li><li><p>Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Universita degli Studi di Genova, Genoa, Italy</p><p>Alberto Martini</p></li><li><p>IRCCS Istituto Giannina Gaslini, Gaslini Trial Centre/Servizio di Sperimentazioni Cliniche Pediatriche, PRINTO, Genoa, Italy</p><p>Nicolino Ruperto</p></li></ol><span>Authors</span><ol><li><span>Hermine I Brunner</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Grant S Schulert</span>View author publications<p>You can also search for this author in <span>PubM","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100621","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 : 2024-08-27DOI: 10.1186/s13075-024-03376-9
Merete Lund Hetland, Anja Strangfeld, Gianluca Bonfanti, Dimitrios Soudis, J Jasper Deuring, Roger A Edwards
Background: Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program.
Methods: This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model.
Results: A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only.
Conclusions: Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction.
背景：类风湿性关节炎（RA）患者发生严重感染（SIs）的风险比没有RA的患者高；预测该患者群体SIs的工作正在进行中。我们利用托法替尼 RA 临床试验项目的基线数据评估了不同机器学习建模方法预测 SI 的能力：该分析包括来自 19 项临床试验（2 期，n = 10；3 期，n = 6；3b/4 期，n = 3）的数据。接受托法替尼5或10毫克、每日两次（BID）治疗的RA患者被纳入分析；接受托法替尼11毫克、每日一次治疗的患者被视为托法替尼5毫克、每日两次。提取了所有可用的患者水平基线变量。采用统计和机器学习方法（逻辑回归、线性核支持向量机、随机森林、极梯度提升树和提升树）评估基线变量与 SI 的关联（仅逻辑回归），并使用选定的基线变量通过 5 倍交叉验证预测 SI。每个预测模型单独处理缺失值：共有8404名接受托法替尼治疗的RA患者符合纳入条件（总随访时间为15310患者年），其中473名患者报告了SI。在其他基线因素中，年龄、既往感染和皮质类固醇的使用与SI显著相关。在对所有研究数据进行 SI 预测建模时，接收者操作特征曲线下面积 (AUROC) 为 0.656 至 0.739。3期和3b/4期研究数据的AUROC值介于0.599至0.730之间，仅ORAL监测数据的AUROC值介于0.563至0.643之间：结论：托法替尼RA临床试验项目中与SI相关的基线因素与已确定的与RA晚期治疗相关的SI风险因素相似。此外，虽然预测SI的模型性能与其他已发表的模型相似，但并未达到准确预测的阈值（AUROC > 0.85）。因此，预测基线SI的发生仍然具有挑战性，而且随着时间的推移，RA的病程变化可能会使预测变得更加复杂。可能需要纳入其他患者相关因素和医疗服务相关因素，并统一模型中的研究持续时间，以提高预测效果：试验注册：ClinicalTrials.gov：NCT00147498；NCT00413660；NCT00550446；NCT00603512；NCT00687193；NCT01164579；NCT00976599；NCT01059864；NCT01359150；NCT02147587；NCT00960440；NCT00847613；NCT00814307；NCT00856544；NCT00853385；NCT01039688；NCT02187055；NCT02831855；NCT02092467。
{"title":"Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib.","authors":"Merete Lund Hetland, Anja Strangfeld, Gianluca Bonfanti, Dimitrios Soudis, J Jasper Deuring, Roger A Edwards","doi":"10.1186/s13075-024-03376-9","DOIUrl":"10.1186/s13075-024-03376-9","url":null,"abstract":"<p><strong>Background: </strong>Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program.</p><p><strong>Methods: </strong>This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model.</p><p><strong>Results: </strong>A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only.</p><p><strong>Conclusions: </strong>Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079014","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}
To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren’s syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model’s reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients. • Having thyroid disease, experiencing prolonged symptoms, reporting subjective dry mouth, and testing positive for rheumatoid factor (RF) were independent risk factors for pSS-RTA patients. • According to the nomogram, the probability of pSS-RTA patients can be identified. • Multi-centre studies and the inclusion of more quantitative indicators may lead to better predictive models.
{"title":"Analysis of risk factors and development of a nomogram prediction model for renal tubular acidosis in primary Sjogren syndrome patients","authors":"Yanzhen Zeng, Runzhi Liu, Shuyi Li, Jingwen Wei, Fei Luo, Yongkang Chen, Dongmei Zhou","doi":"10.1186/s13075-024-03383-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03383-w","url":null,"abstract":"To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren’s syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model’s reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients. • Having thyroid disease, experiencing prolonged symptoms, reporting subjective dry mouth, and testing positive for rheumatoid factor (RF) were independent risk factors for pSS-RTA patients. • According to the nomogram, the probability of pSS-RTA patients can be identified. • Multi-centre studies and the inclusion of more quantitative indicators may lead to better predictive models.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021842","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 : 2024-08-22DOI: 10.1186/s13075-024-03382-x
Chia-Tse Weng, Tang-Hsiu Huang, Chun-Hsin Wu, Yuan-Ting Sun
Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth’s logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.
{"title":"Association of anti-Ro-52 antibodies with occurrence of interstitial lung disease in patients with idiopathic inflammatory myopathy","authors":"Chia-Tse Weng, Tang-Hsiu Huang, Chun-Hsin Wu, Yuan-Ting Sun","doi":"10.1186/s13075-024-03382-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03382-x","url":null,"abstract":"Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth’s logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142022048","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}
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