Yiwei Shen, Jingyi Peng, Dai Dai, Min Dai, Ting Li, Sheng Chen, Shuang Ye, Nan Shen, Huihua Ding
Objective To investigate the clinical characteristics, renal pathology treatment responses, and renal outcomes of lupus nephritis (LN) patients with different levels of baseline proteinuria. Methods A total of 239 biopsy‐proven LN patients were stratified by baseline proteinuria (UPro) levels (<1g/24h vs. ≥1g/24h) and disease onset status (incident vs. relapsing). Renal treatment responses were measured by overall response (OR), complete response, and primary efficacy renal response at weeks 26 and 52. Cox proportional hazards regression and Kaplan‐Meier analyses were used to assess predictors of time to first 30% and 40% eGFR decline by 156 weeks. Results Among the 239 LN patients, 42 (17.6%) had UPro <1g/24h, and 197 (82.4%) had UPro ≥1g/24h; 122 (51.0%) had incident LN and 117 (49.0%) had relapsing LN. The UPro <1 group had a lower incidence of urinary sediments, a higher frequency of Class V, and a lower renal pathology activity index, but similar chronicity index compared to the UPro ≥1 group. Both groups exhibited similar OR rates at weeks 26 and 52. Patients with low‐grade proteinuria had equivalent risk probabilities for experiencing a 30% or 40% decline in eGFR over 156 weeks compared to those with high‐grade proteinuria. Glomerulosclerosis independently predict long‐term renal deterioration in relapsing, but not incident LN. Conclusion Low‐grade proteinuria (UPro <1g/24h) doesn't confer better renal outcomes or treatment response in LN. Glomerulosclerosis predicts renal function decline in relapsing LN. These results underscore the importance of early biopsy, personalized therapy, and close monitoring, supported by non‐invasive biomarkers for risk assessment.
{"title":"Low‐Grade Proteinuria Does Not Predict Favorable Outcomes in Lupus Nephritis: A Longitudinal Cohort Study","authors":"Yiwei Shen, Jingyi Peng, Dai Dai, Min Dai, Ting Li, Sheng Chen, Shuang Ye, Nan Shen, Huihua Ding","doi":"10.1002/art.70009","DOIUrl":"https://doi.org/10.1002/art.70009","url":null,"abstract":"Objective To investigate the clinical characteristics, renal pathology treatment responses, and renal outcomes of lupus nephritis (LN) patients with different levels of baseline proteinuria. Methods A total of 239 biopsy‐proven LN patients were stratified by baseline proteinuria (UPro) levels (<1g/24h vs. ≥1g/24h) and disease onset status (incident vs. relapsing). Renal treatment responses were measured by overall response (OR), complete response, and primary efficacy renal response at weeks 26 and 52. Cox proportional hazards regression and Kaplan‐Meier analyses were used to assess predictors of time to first 30% and 40% eGFR decline by 156 weeks. Results Among the 239 LN patients, 42 (17.6%) had UPro <1g/24h, and 197 (82.4%) had UPro ≥1g/24h; 122 (51.0%) had incident LN and 117 (49.0%) had relapsing LN. The UPro <1 group had a lower incidence of urinary sediments, a higher frequency of Class V, and a lower renal pathology activity index, but similar chronicity index compared to the UPro ≥1 group. Both groups exhibited similar OR rates at weeks 26 and 52. Patients with low‐grade proteinuria had equivalent risk probabilities for experiencing a 30% or 40% decline in eGFR over 156 weeks compared to those with high‐grade proteinuria. Glomerulosclerosis independently predict long‐term renal deterioration in relapsing, but not incident LN. Conclusion Low‐grade proteinuria (UPro <1g/24h) doesn't confer better renal outcomes or treatment response in LN. Glomerulosclerosis predicts renal function decline in relapsing LN. These results underscore the importance of early biopsy, personalized therapy, and close monitoring, supported by non‐invasive biomarkers for risk assessment.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"172 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reinterpreting the Efficacy of IL ‐1 Inhibitors in VEXAS Syndrome: A Matter of Superiority or Sequencing?","authors":"Zhenguo Ding, Tiantian Zhang, Susu Zhang","doi":"10.1002/art.70006","DOIUrl":"https://doi.org/10.1002/art.70006","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"149 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deanna Jannat‐Khah, Jeffrey R. Curtis, Fenglong Xie, Ashish Saxena, Anne R. Bass
Objective Glucocorticoids are commonly used for rheumatoid arthritis (RA) treatment and to palliate some malignancies, but it is unclear whether glucocorticoids attenuate the benefits of immune checkpoint inhibitor (ICI) cancer therapy. We examined the association between glucocorticoid use and survival among ICI‐treated RA patients with metastatic non‐small cell lung cancer (mNSCLC). Methods A cohort of RA patients enrolled in Medicare were identified based on: age ≥66 years, RA diagnosed prior to mNSCLC, initiated nivolumab, pembrolizumab or atezolizumab (2015‐2019, when approved only for mNSCLC). Landmark Kaplan Meier (KM) curves and time‐varying adjusted Cox models were used to examine the association between early glucocorticoid use (within 91 days after ICI initiation) and survival. Dexamethasone users were excluded from the primary analysis and included in a sensitivity analysis. Results We identified 663 ICI‐treated RA patients with mNSCLC, mean age 75, 86.9% White, 64.7% female, 363 (46%) received glucocorticoids. Among users, median [IQR] average prednisone‐equivalents was 6.59 mg/d [IQR: 3.30, 12.31]. In a time‐varying Cox model, glucocorticoid use was not associated with survival. Additionally, in a 91 day landmark model, glucocorticoid dose was not associated with survival [HR 1.01 95%CI [0.93, 1.10]. Conclusion Glucocorticoids, at the dosages used to treat ICI‐treated RA patients with mNSCLC, had a negligible effect on survival in the 91 days after ICI initiation.
{"title":"Are Glucocorticoids Associated with Worse Survival among Rheumatoid Arthritis Patients with Lung Cancer Treated with Immune Checkpoint Inhibitors?","authors":"Deanna Jannat‐Khah, Jeffrey R. Curtis, Fenglong Xie, Ashish Saxena, Anne R. Bass","doi":"10.1002/art.43445","DOIUrl":"https://doi.org/10.1002/art.43445","url":null,"abstract":"Objective Glucocorticoids are commonly used for rheumatoid arthritis (RA) treatment and to palliate some malignancies, but it is unclear whether glucocorticoids attenuate the benefits of immune checkpoint inhibitor (ICI) cancer therapy. We examined the association between glucocorticoid use and survival among ICI‐treated RA patients with metastatic non‐small cell lung cancer (mNSCLC). Methods A cohort of RA patients enrolled in Medicare were identified based on: age ≥66 years, RA diagnosed prior to mNSCLC, initiated nivolumab, pembrolizumab or atezolizumab (2015‐2019, when approved only for mNSCLC). Landmark Kaplan Meier (KM) curves and time‐varying adjusted Cox models were used to examine the association between early glucocorticoid use (within 91 days after ICI initiation) and survival. Dexamethasone users were excluded from the primary analysis and included in a sensitivity analysis. Results We identified 663 ICI‐treated RA patients with mNSCLC, mean age 75, 86.9% White, 64.7% female, 363 (46%) received glucocorticoids. Among users, median [IQR] average prednisone‐equivalents was 6.59 mg/d [IQR: 3.30, 12.31]. In a time‐varying Cox model, glucocorticoid use was not associated with survival. Additionally, in a 91 day landmark model, glucocorticoid dose was not associated with survival [HR 1.01 95%CI [0.93, 1.10]. Conclusion Glucocorticoids, at the dosages used to treat ICI‐treated RA patients with mNSCLC, had a negligible effect on survival in the 91 days after ICI initiation.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"109 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jumei Yang, Wenjun Li, Jiarui Zhu, Xi Cui, Hui Chai, Qiyan Su, Jin Guo, Yingyue Feng, Zhuanhui Huang, Yun Lv, Sigong Zhang
Objectives Interstitial lung disease (ILD) is the most common and prognostically severe complication of idiopathic inflammatory myopathy (IIM), for which targeted treatments remain limited. Based on previous findings that neutrophil extracellular traps (NETs) are key mediators in IIM‐ILD pathogenesis and given the established role of IL‐33 in promoting NETosis, we hypothesized. Methods We integrated analyses of human IIM‐ILD samples with a myositis‐ associated ILD (MAILD) mouse model employing IL‐33–knockout (KO) and reconstitution strategies. The ERK pathway was inhibited in vivo with U0126. In vitro, IL‐33–knockdown (KD) alveolar epithelial cells were challenged with NETs. Assessments included ELISA, IHC/IF, WB, and RNA sequencing.. Results Serum IL‐33 levels were significantly elevated in IIM–ILD patients compared with healthy controls, with concurrent upregulation of IL‐33 in lung tissues. MAILD mice similarly showed increased IL‐33 expression, whereas IL‐33 KO mice exhibited attenuated lung inflammation, improved alveolar architecture, and decreased collagen deposition. Administration of exogenous IL‐33 restored ILD severity in IL‐33 KO mice to wild‐type levels. The levels of p‐ERK and EMT markers (E‐Ca, α‐SMA) correlated with IL‐33 expression. U0126 reduced p‐ERK levels, suppressed EMT, and ameliorated both pulmonary inflammation and fibrosis. In vitro, NETs induced EMT and ERK activation in A549 cells, effects that were abolished upon IL‐33 silencing. Conclusions IL‐33 promotes IIM–ILD progression by activating ERK‐dependent EMT, identifying the IL‐33/ERK signaling axis as a potential therapeutic target. These results provide mechanistic insight into IIM–ILD pathogenesis and support translational strategies for precision intervention.
{"title":"Interleukin‐33 Promotes Interstitial Lung Disease in Idiopathic Inflammatory Myopathy via ERK‐Mediated Epithelial‐Mesenchymal Transition: ERK as a potential therapeutic target","authors":"Jumei Yang, Wenjun Li, Jiarui Zhu, Xi Cui, Hui Chai, Qiyan Su, Jin Guo, Yingyue Feng, Zhuanhui Huang, Yun Lv, Sigong Zhang","doi":"10.1002/art.43453","DOIUrl":"https://doi.org/10.1002/art.43453","url":null,"abstract":"Objectives Interstitial lung disease (ILD) is the most common and prognostically severe complication of idiopathic inflammatory myopathy (IIM), for which targeted treatments remain limited. Based on previous findings that neutrophil extracellular traps (NETs) are key mediators in IIM‐ILD pathogenesis and given the established role of IL‐33 in promoting NETosis, we hypothesized. Methods We integrated analyses of human IIM‐ILD samples with a myositis‐ associated ILD (MAILD) mouse model employing IL‐33–knockout (KO) and reconstitution strategies. The ERK pathway was inhibited in vivo with U0126. In vitro, IL‐33–knockdown (KD) alveolar epithelial cells were challenged with NETs. Assessments included ELISA, IHC/IF, WB, and RNA sequencing.. Results Serum IL‐33 levels were significantly elevated in IIM–ILD patients compared with healthy controls, with concurrent upregulation of IL‐33 in lung tissues. MAILD mice similarly showed increased IL‐33 expression, whereas IL‐33 KO mice exhibited attenuated lung inflammation, improved alveolar architecture, and decreased collagen deposition. Administration of exogenous IL‐33 restored ILD severity in IL‐33 KO mice to wild‐type levels. The levels of p‐ERK and EMT markers (E‐Ca, α‐SMA) correlated with IL‐33 expression. U0126 reduced p‐ERK levels, suppressed EMT, and ameliorated both pulmonary inflammation and fibrosis. In vitro, NETs induced EMT and ERK activation in A549 cells, effects that were abolished upon IL‐33 silencing. Conclusions IL‐33 promotes IIM–ILD progression by activating ERK‐dependent EMT, identifying the IL‐33/ERK signaling axis as a potential therapeutic target. These results provide mechanistic insight into IIM–ILD pathogenesis and support translational strategies for precision intervention.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"121 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to Editor: The limitations on Urate's Role in Knee Osteoarthritis Studies","authors":"Qing Wang, Shuxing Xing","doi":"10.1002/art.43448","DOIUrl":"https://doi.org/10.1002/art.43448","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"90 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharon Dowell, Emily E. Holladay, Jeffrey R. Curtis, Gail S. Kerr
{"title":"Reply to Redlining, Structural Racism, and Psoriatic Arthritis Outcomes","authors":"Sharon Dowell, Emily E. Holladay, Jeffrey R. Curtis, Gail S. Kerr","doi":"10.1002/art.43454","DOIUrl":"https://doi.org/10.1002/art.43454","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alex Hlavaty, Loubna Dari, Jean‐Luc Cracowski, Matthieu Roustit, Charles Khouri
Objectives The aim of this study is to generate hypotheses about unknown drugs associated with the onset or worsening of Raynaud's Phenomenon (RP) and to explore their potential pathophysiological mechanisms through a mixed disproportionality/clustering analysis from the WHO pharmacovigilance database. Methods Using the WHO Pharmacovigilance database, we identified cases using the Preferred Term “Raynaud's phenomenon” and we excluded all Individual Case Safety Reports (ICSRs) associated with at least one drug used in RP treatment. To estimate signals of disproportionate reporting (SDR) we calculated Information Component (IC) values (IC LB >0 deemed significant). We performed several sensitivity analyses to assess the robustness of the results. We evaluated and prioritized the plausibility of signals according to expert review of cases characteristics, robustness of results, and pharmacological hypotheses. Lastly, to explore pathophysiological mechanisms, we used drug target extraction from DrugBank and a clustering method to identify similar patterns of adverse events reporting. Results We included 4,430 ICSRs of Raynaud's phenomenon in our analysis. We found 124 significant SDRs in the primary analysis, of which 52 SDRs were consistent across all sensitivity analyses, and 16 were considered probable after signal evaluation and prioritization; including amphetamine‐like, antimigraine drugs, antineoplastics drugs and dopaminergic agonists. Most of the targets involved were 5‐HT1A‐R, sodium‐dependent noradrenaline transporter, and beta‐1 and beta‐2 adrenergic receptors. Cluster analyses yielded inconsistent results according to the method used. Conclusion This study allowed us to identify robust safety signals (such as solriamfetol, tyrosine kinase inhibitors and CGRP inhibitors) for drugs associated with RP and potential implicated pathophysiological mechanisms. image
{"title":"Drugs induced Raynaud's phenomenon and underlying mechanism: a disproportionality analysis from the WHO pharmacovigilance database","authors":"Alex Hlavaty, Loubna Dari, Jean‐Luc Cracowski, Matthieu Roustit, Charles Khouri","doi":"10.1002/art.43442","DOIUrl":"https://doi.org/10.1002/art.43442","url":null,"abstract":"Objectives The aim of this study is to generate hypotheses about unknown drugs associated with the onset or worsening of Raynaud's Phenomenon (RP) and to explore their potential pathophysiological mechanisms through a mixed disproportionality/clustering analysis from the WHO pharmacovigilance database. Methods Using the WHO Pharmacovigilance database, we identified cases using the Preferred Term “Raynaud's phenomenon” and we excluded all Individual Case Safety Reports (ICSRs) associated with at least one drug used in RP treatment. To estimate signals of disproportionate reporting (SDR) we calculated Information Component (IC) values (IC <jats:sub>LB</jats:sub> >0 deemed significant). We performed several sensitivity analyses to assess the robustness of the results. We evaluated and prioritized the plausibility of signals according to expert review of cases characteristics, robustness of results, and pharmacological hypotheses. Lastly, to explore pathophysiological mechanisms, we used drug target extraction from DrugBank and a clustering method to identify similar patterns of adverse events reporting. Results We included 4,430 ICSRs of Raynaud's phenomenon in our analysis. We found 124 significant SDRs in the primary analysis, of which 52 SDRs were consistent across all sensitivity analyses, and 16 were considered probable after signal evaluation and prioritization; including amphetamine‐like, antimigraine drugs, antineoplastics drugs and dopaminergic agonists. Most of the targets involved were 5‐HT1A‐R, sodium‐dependent noradrenaline transporter, and beta‐1 and beta‐2 adrenergic receptors. Cluster analyses yielded inconsistent results according to the method used. Conclusion This study allowed us to identify robust safety signals (such as solriamfetol, tyrosine kinase inhibitors and CGRP inhibitors) for drugs associated with RP and potential implicated pathophysiological mechanisms. <jats:boxed-text content-type=\"graphic\" position=\"anchor\"> <jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/art43442-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"177 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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