Brent A Luedders,Daniel Kass,Joshua F Baker,Michael J Duryee,Yangyuna Yang,Punyasha Roul,Halie Frideres,Katherine D Wysham,Paul A Monach,Andreas Reimold,Gail S Kerr,Gary Kunkel,Grant W Cannon,Scott M Matson,Jill A Poole,Geoffrey M Thiele,Ted R Mikuls,Bryant R England,Dana P Ascherman
OBJECTIVETo assess whether a panel of peripheral blood biomarkers associated with idiopathic pulmonary fibrosis (IPF) is also associated with interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) utilizing three independent cohorts.METHODSWe first assessed the association of a panel of IPF-associated biomarkers with prevalent ILD among two separate RA cohorts (n=93 and n=71). Concentrations of eight IPF-related biomarkers (eotaxin, Flt-3L, IL-8, MDC, MCP-1, and MMP-2/7/9) were measured, standardized, and summed to generate a multibiomarker score. We subsequently validated the association of this score (minus MMP-2) with prevalent and incident ILD in an independent multicenter, prospective cohort of US Veterans with RA (n=2,507). Multivariable regression models were adjusted for relevant covariates in the validation cohort.RESULTSIn both development cohorts, participants with RA-ILD had significantly higher IPF multibiomarker scores than those with RA alone. In the independent validation cohort, participants with the highest quartile multibiomarker scores had a significantly higher likelihood of prevalent ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) than those in the lowest quartile. The cumulative hazard of incident ILD approached 20% by 15 years for those in the highest quartile compared to <10% for all other quartiles.CONCLUSIONA multibiomarker panel derived from IPF-associated biomarkers was associated with RA-ILD in separate development and validation cohorts. This overlap supports the concept of shared etiopathogenesis of IPF and RA-ILD and illustrates the potential for peripheral blood biomarker panels to stratify ILD risk among RA patients.
目的：利用三个独立的队列，评估与特发性肺纤维化（IPF）相关的一组外周血生物标志物是否也与类风湿关节炎（RA）患者间质性肺疾病（ILD）相关。方法：我们首先评估了两组独立RA队列（n=93和n=71）中ipf相关生物标志物与ILD的相关性。测量8种ipf相关生物标志物（eotaxin, Flt-3L, IL-8， MDC， MCP-1和MMP-2/7/9）的浓度，标准化并汇总以产生多生物标志物评分。随后，我们在一个独立的多中心前瞻性美国退伍军人RA队列（n= 2507）中验证了该评分（- MMP-2）与常见和偶发ILD的关联。在验证队列中对多变量回归模型进行相关协变量调整。结果在两个研究队列中，RA- ild患者的IPF多生物标志物评分均显著高于单纯RA患者。在独立验证队列中，四分位数多生物标志物评分最高的参与者与最低四分位数的参与者相比，患病率ILD（校正优势比2.14 [95% CI 1.18-3.87]）和发生率ILD（校正风险比2.45 [95% CI 1.55-3.88]）的可能性显著更高。在最高的四分位数中，发生ILD的累积风险在15年内接近20%，而其他四分位数的累积风险小于10%。结论：在单独的研究和验证队列中，由ipf相关生物标志物衍生的多生物标志物组与RA-ILD相关。这种重叠支持IPF和RA-ILD共同发病机制的概念，并说明外周血生物标志物面板对RA患者ILD风险分层的潜力。
{"title":"Performance of an Idiopathic Pulmonary Fibrosis Derived Multibiomarker Panel for Rheumatoid Arthritis-Associated Interstitial Lung Disease.","authors":"Brent A Luedders,Daniel Kass,Joshua F Baker,Michael J Duryee,Yangyuna Yang,Punyasha Roul,Halie Frideres,Katherine D Wysham,Paul A Monach,Andreas Reimold,Gail S Kerr,Gary Kunkel,Grant W Cannon,Scott M Matson,Jill A Poole,Geoffrey M Thiele,Ted R Mikuls,Bryant R England,Dana P Ascherman","doi":"10.1002/art.43383","DOIUrl":"https://doi.org/10.1002/art.43383","url":null,"abstract":"OBJECTIVETo assess whether a panel of peripheral blood biomarkers associated with idiopathic pulmonary fibrosis (IPF) is also associated with interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) utilizing three independent cohorts.METHODSWe first assessed the association of a panel of IPF-associated biomarkers with prevalent ILD among two separate RA cohorts (n=93 and n=71). Concentrations of eight IPF-related biomarkers (eotaxin, Flt-3L, IL-8, MDC, MCP-1, and MMP-2/7/9) were measured, standardized, and summed to generate a multibiomarker score. We subsequently validated the association of this score (minus MMP-2) with prevalent and incident ILD in an independent multicenter, prospective cohort of US Veterans with RA (n=2,507). Multivariable regression models were adjusted for relevant covariates in the validation cohort.RESULTSIn both development cohorts, participants with RA-ILD had significantly higher IPF multibiomarker scores than those with RA alone. In the independent validation cohort, participants with the highest quartile multibiomarker scores had a significantly higher likelihood of prevalent ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) than those in the lowest quartile. The cumulative hazard of incident ILD approached 20% by 15 years for those in the highest quartile compared to <10% for all other quartiles.CONCLUSIONA multibiomarker panel derived from IPF-associated biomarkers was associated with RA-ILD in separate development and validation cohorts. This overlap supports the concept of shared etiopathogenesis of IPF and RA-ILD and illustrates the potential for peripheral blood biomarker panels to stratify ILD risk among RA patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"19 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068248","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}
BACKGROUNDCaspase-4/5/11 mediated noncanonical pyroptosis emerges as a contributing factor in immune responses under pathological conditions. However, its precise role in the development of lupus nephritis (LN) remains largely unknown. Although mesenchymal stromal cells (MSCs) have demonstrated promising therapeutic effects on LN, whether MSCs influence pyroptosis in macrophages remains unknown. This study aimed to elucidate the role of caspase-4/5/11-mediated noncanonical pyroptosis in macrophages during the pathogenesis of LN and explore the impact of MSCs on macrophages.METHODSThe expression level of noncanonical pyroptosis in macrophages was assessed in patients and mice with LN. Blood samples from 19 refractory SLE patients receiving MSCs transplantation (MSCT) were collected. Caspase-11 inhibitor wedelolactone and MSCs were administered to MRL/lpr mice to examine the therapeutic efficacy. MSCs were co-cultured with macrophages from MRL/lpr mice to explore effects and related mechanisms.RESULTSNoncanonical pyroptosis signaling was activated in macrophages and kidney tissues from humans and mice with LN. The expression level of caspase-4 was increased and positively correlated with the active index and chronic index in the kidneys of LN patients. The end products of pyroptosis directly induced cell death and reduced functional markers expression in murine podocytes. The caspase-11 inhibitor effectively alleviated renal damage in lupus mice. MSCT significantly deactivated pyroptosis signaling both in patients and lupus-prone mice. Mechanically, galectin-3 and interleukin-10 (IL-10) are essential for MSCs to inhibit noncanonical pyroptosis of LN macrophages.CONCLUSIONSOur findings showed that MSCT ameliorates LN by inhibiting the caspase-4/5/11-mediated pyroptosis in macrophages, possibly via secreting galectin-3 and IL-10.
{"title":"Mesenchymal Stromal Cell Therapy Alleviates Lupus Nephritis Through Inhibiting Caspase-4/5/11-mediated Noncanonical Pyroptosis in Macrophages.","authors":"Sha Liu,Zhikang Wang,Yue Zhang,Panpan Zhou,Huimin Zhu,Yang Hang,Xue Xu,Xiaojun Tang,Genhong Yao,Dandan Wang,Linyu Geng,Weiwei Chen,Lingyun Sun","doi":"10.1002/art.43380","DOIUrl":"https://doi.org/10.1002/art.43380","url":null,"abstract":"BACKGROUNDCaspase-4/5/11 mediated noncanonical pyroptosis emerges as a contributing factor in immune responses under pathological conditions. However, its precise role in the development of lupus nephritis (LN) remains largely unknown. Although mesenchymal stromal cells (MSCs) have demonstrated promising therapeutic effects on LN, whether MSCs influence pyroptosis in macrophages remains unknown. This study aimed to elucidate the role of caspase-4/5/11-mediated noncanonical pyroptosis in macrophages during the pathogenesis of LN and explore the impact of MSCs on macrophages.METHODSThe expression level of noncanonical pyroptosis in macrophages was assessed in patients and mice with LN. Blood samples from 19 refractory SLE patients receiving MSCs transplantation (MSCT) were collected. Caspase-11 inhibitor wedelolactone and MSCs were administered to MRL/lpr mice to examine the therapeutic efficacy. MSCs were co-cultured with macrophages from MRL/lpr mice to explore effects and related mechanisms.RESULTSNoncanonical pyroptosis signaling was activated in macrophages and kidney tissues from humans and mice with LN. The expression level of caspase-4 was increased and positively correlated with the active index and chronic index in the kidneys of LN patients. The end products of pyroptosis directly induced cell death and reduced functional markers expression in murine podocytes. The caspase-11 inhibitor effectively alleviated renal damage in lupus mice. MSCT significantly deactivated pyroptosis signaling both in patients and lupus-prone mice. Mechanically, galectin-3 and interleukin-10 (IL-10) are essential for MSCs to inhibit noncanonical pyroptosis of LN macrophages.CONCLUSIONSOur findings showed that MSCT ameliorates LN by inhibiting the caspase-4/5/11-mediated pyroptosis in macrophages, possibly via secreting galectin-3 and IL-10.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"35 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068244","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}
Nancy J Olsen,Duanping Liao,Judith A James,Joel M Guthridge,Cristina Arriens,Diane Kamen,Mariko Ishimori,Daniel J Wallace,Christopher Striebich,Sonali Narain,Benjamin F Chong,Fan He,Eric W Schaefer,Vernon M Chinchilli,David R Karp
OBJECTIVESPatients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity and incidence of SLE.METHODSHydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether rate of accumulation of SLE features defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with 1-2 additional criteria. Patients 15-49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit.RESULTSParticipants (n=187) were randomized at 7 sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 on HCQ and 88 on placebo. The mean age was 33 years, 91.1% were female and 74.4% were white. SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P=0.72 and P=0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness or pleurisy (P<0.04).CONCLUSIONWhile SMILE did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population. With development of biomarkers, designing targeted prevention strategies should be feasible.
{"title":"A randomized, placebo-controlled trial of hydroxychloroquine in incomplete lupus.","authors":"Nancy J Olsen,Duanping Liao,Judith A James,Joel M Guthridge,Cristina Arriens,Diane Kamen,Mariko Ishimori,Daniel J Wallace,Christopher Striebich,Sonali Narain,Benjamin F Chong,Fan He,Eric W Schaefer,Vernon M Chinchilli,David R Karp","doi":"10.1002/art.43391","DOIUrl":"https://doi.org/10.1002/art.43391","url":null,"abstract":"OBJECTIVESPatients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity and incidence of SLE.METHODSHydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether rate of accumulation of SLE features defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with 1-2 additional criteria. Patients 15-49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit.RESULTSParticipants (n=187) were randomized at 7 sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 on HCQ and 88 on placebo. The mean age was 33 years, 91.1% were female and 74.4% were white. SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P=0.72 and P=0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness or pleurisy (P<0.04).CONCLUSIONWhile SMILE did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population. With development of biomarkers, designing targeted prevention strategies should be feasible.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"83 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068243","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}
Rong Fu,Afroditi Boulougoura,Shuilian Yu,Hao Li,Wenliang Pan,Yushiro Endo,Rhea Bhargava,Abhiyan Satyam,Vivek Kasinath,Jarrat Jordan,Nandan Padmanabha,Maria G Tsokos,Reza Abdi,George C Tsokos
OBJECTIVEUpregulation of Interleukin 23 (IL-23) in the serum and kidneys of patients with lupus nephritis (LN) has been demonstrated, but its effect on podocytes remains unknown. We hypothesized that IL-23 contributes to podocyte injury and that targeted deletion of IL-23R in podocytes of lupus-prone mice can prevent the development of glomerulonephritis.METHODSKidney biopsies were immunostained for IL-23R. In vitro experiments were conducted using a human podocyte cell line and primary murine podocytes. Human podocytes stimulated with IL-23 underwent bulk-RNA sequencing. The expression of IL-23R, structure and motility of podocytes were assessed. Podocytes isolated from B6 wild type mice injected with a minicircle (MC) encoding IL-23 were studied. To assess the role of IL-23R in the development of nephritis, we generated podocyte-specific Il23r deficient MRL/lpr lupus-prone mice.RESULTSIL-23R was highly expressed in the glomeruli of patients with LN. IL-23R expression was also upregulated in human podocytes and primary podocytes isolated from B6 mice after IL-23 stimulation. Human podocytes stimulated with IL-23 showed decreased expression of synaptopodin and remodeling of the actin cytoskeleton. IL-23 MC-administered mice exhibited a significant increase in the expression of IL-23R and phosphorylated STAT3 (pSTAT3) in podocytes. Finally, MRL/lpr.Podo-Cre+ Il23rfl/fl mice showed decreased clinical and histologic features of LN.CONCLUSIONIL-23R expression is increased in podocytes from mice and humans with systemic lupus erythematosus. IL-23 signaling disrupts the cytoskeleton in podocytes and increases their mobility leading to the development of glomerulonephritis. Podocyte-specific deletion of Il23r in lupus-prone mice abrogates the development of LN.
{"title":"Interleukin-23 receptor deficiency in podocytes averts the development of lupus nephritis.","authors":"Rong Fu,Afroditi Boulougoura,Shuilian Yu,Hao Li,Wenliang Pan,Yushiro Endo,Rhea Bhargava,Abhiyan Satyam,Vivek Kasinath,Jarrat Jordan,Nandan Padmanabha,Maria G Tsokos,Reza Abdi,George C Tsokos","doi":"10.1002/art.43395","DOIUrl":"https://doi.org/10.1002/art.43395","url":null,"abstract":"OBJECTIVEUpregulation of Interleukin 23 (IL-23) in the serum and kidneys of patients with lupus nephritis (LN) has been demonstrated, but its effect on podocytes remains unknown. We hypothesized that IL-23 contributes to podocyte injury and that targeted deletion of IL-23R in podocytes of lupus-prone mice can prevent the development of glomerulonephritis.METHODSKidney biopsies were immunostained for IL-23R. In vitro experiments were conducted using a human podocyte cell line and primary murine podocytes. Human podocytes stimulated with IL-23 underwent bulk-RNA sequencing. The expression of IL-23R, structure and motility of podocytes were assessed. Podocytes isolated from B6 wild type mice injected with a minicircle (MC) encoding IL-23 were studied. To assess the role of IL-23R in the development of nephritis, we generated podocyte-specific Il23r deficient MRL/lpr lupus-prone mice.RESULTSIL-23R was highly expressed in the glomeruli of patients with LN. IL-23R expression was also upregulated in human podocytes and primary podocytes isolated from B6 mice after IL-23 stimulation. Human podocytes stimulated with IL-23 showed decreased expression of synaptopodin and remodeling of the actin cytoskeleton. IL-23 MC-administered mice exhibited a significant increase in the expression of IL-23R and phosphorylated STAT3 (pSTAT3) in podocytes. Finally, MRL/lpr.Podo-Cre+ Il23rfl/fl mice showed decreased clinical and histologic features of LN.CONCLUSIONIL-23R expression is increased in podocytes from mice and humans with systemic lupus erythematosus. IL-23 signaling disrupts the cytoskeleton in podocytes and increases their mobility leading to the development of glomerulonephritis. Podocyte-specific deletion of Il23r in lupus-prone mice abrogates the development of LN.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"76 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058888","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}
OBJECTIVEMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.METHODSWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.RESULTSZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.CONCLUSIONZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.
{"title":"ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis.","authors":"Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang","doi":"10.1002/art.43393","DOIUrl":"https://doi.org/10.1002/art.43393","url":null,"abstract":"OBJECTIVEMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.METHODSWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.RESULTSZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.CONCLUSIONZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058887","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}
Zhenyu Zhong,Jiayi Wang,Lan Xia,Shixiang Jing,Yujie Lai,Tao Cai,Peizeng Yang
PURPOSETo evaluate comparative effectiveness of cyclosporine, interferon alfa-2a, and adalimumab for the prevention of uveitis relapse in Behçet's disease in real-world settings.METHODSWe emulated a target trial involving adult patients with Behçet's disease uveitis who initiated cyclosporine, interferon alfa-2a, or adalimumab between April 10, 2008, and August 1, 2024, and were followed up until September 10, 2024. We applied overlap weighting to balance patient characteristics across treatment groups and emulate randomization at baseline. The primary outcome was the annualized relapse rate of uveitis during treatment with study therapy.RESULTSThe cohort comprised 716 cyclosporine users, 193 interferon alfa-2a users, and 103 adalimumab users. The estimated mean annualized relapse rate of uveitis was 0.95 (95%, 0.82 to 1.10) with cyclosporine, 0.52 (95%, 0.40 to 0.69) with interferon alfa-2a, and 0.28 (95%, 0.19 to 0.43) with adalimumab. Patients treated with cyclosporine experienced more relapses than those treated with adalimumab (incidence rate ratio [IRR], 3.36 [95% CI, 2.23 to 5.05]; mean difference, 0.66 [95% CI, 0.48 to 0.85]; P<0.001) or interferon alfa-2a (IRR, 1.81 [95% CI, 1.37 to 2.40]; mean difference, 0.42 [95% CI, 0.22 to 0.62]; P<0.001). The relapse rate was higher with interferon alfa-2a than with adalimumab (IRR, 1.86 [95% CI, 1.16 to 2.97]; mean difference, 0.24 [95% CI, 0.05 to 0.43]; P=0.011).CONCLUSIONIn Behçet's disease, interferon alfa-2a was associated with a reduction in uveitis relapse compared with cyclosporine, while adalimumab demonstrated a stronger association with reduced relapse than interferon alfa-2a.
{"title":"Comparative Real-World Effectiveness of Immunomodulatory Therapies for Prevention of Uveitis Relapse in Behçet's Disease.","authors":"Zhenyu Zhong,Jiayi Wang,Lan Xia,Shixiang Jing,Yujie Lai,Tao Cai,Peizeng Yang","doi":"10.1002/art.43382","DOIUrl":"https://doi.org/10.1002/art.43382","url":null,"abstract":"PURPOSETo evaluate comparative effectiveness of cyclosporine, interferon alfa-2a, and adalimumab for the prevention of uveitis relapse in Behçet's disease in real-world settings.METHODSWe emulated a target trial involving adult patients with Behçet's disease uveitis who initiated cyclosporine, interferon alfa-2a, or adalimumab between April 10, 2008, and August 1, 2024, and were followed up until September 10, 2024. We applied overlap weighting to balance patient characteristics across treatment groups and emulate randomization at baseline. The primary outcome was the annualized relapse rate of uveitis during treatment with study therapy.RESULTSThe cohort comprised 716 cyclosporine users, 193 interferon alfa-2a users, and 103 adalimumab users. The estimated mean annualized relapse rate of uveitis was 0.95 (95%, 0.82 to 1.10) with cyclosporine, 0.52 (95%, 0.40 to 0.69) with interferon alfa-2a, and 0.28 (95%, 0.19 to 0.43) with adalimumab. Patients treated with cyclosporine experienced more relapses than those treated with adalimumab (incidence rate ratio [IRR], 3.36 [95% CI, 2.23 to 5.05]; mean difference, 0.66 [95% CI, 0.48 to 0.85]; P<0.001) or interferon alfa-2a (IRR, 1.81 [95% CI, 1.37 to 2.40]; mean difference, 0.42 [95% CI, 0.22 to 0.62]; P<0.001). The relapse rate was higher with interferon alfa-2a than with adalimumab (IRR, 1.86 [95% CI, 1.16 to 2.97]; mean difference, 0.24 [95% CI, 0.05 to 0.43]; P=0.011).CONCLUSIONIn Behçet's disease, interferon alfa-2a was associated with a reduction in uveitis relapse compared with cyclosporine, while adalimumab demonstrated a stronger association with reduced relapse than interferon alfa-2a.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"36 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058953","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":"Less Is More: Hematologic Safety and Sustained Efficacy of a Modified Low-dose Etoposide Regimen in MAS.","authors":"Zijun Ma,Xiaoquan Rao,Yingying Wei,Wei Tu,Jixin Zhong","doi":"10.1002/art.43390","DOIUrl":"https://doi.org/10.1002/art.43390","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"72 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059230","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":"\"Negative\" finding supports two-hit model: comment on the article by Kroese et al.","authors":"Ronald van Vollenhoven","doi":"10.1002/art.43385","DOIUrl":"10.1002/art.43385","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062938","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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