{"title":"Klippel-Feil Syndrome in a Patient Referred for Axial Spondyloarthritis.","authors":"Zeyu Tang,Brian Buonocore,Abhijeet Danve","doi":"10.1002/art.70023","DOIUrl":"https://doi.org/10.1002/art.70023","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"230 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752721","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}
Qi Zheng,Yejun Tan,Zhaoling Wang,Yanjie Qian,Qian Ma,Danping Shen,Meiping Lu
OBJECTIVEThis study aimed to investigate the mechanisms of immune dysregulation in a pediatric patient with monogenic lupus driven by IKZF1-haploinsufficiency.METHODSPeripheral immune cells from patient with IKZF1-haploinsufficiency, lupus cases with no currently known genetic mutations, and healthy controls were analyzed using single-cell RNA sequencing. Bioinformatic analyses, including pseudotime trajectory and network reconstruction were performed. Activation of type I interferon (IFN) pathway was evaluated by measuring serum cytokine levels, IFN signatures, and the phosphorylation status of Janus kinase (JAK) and signal transducer and activator of transcription (STAT).RESULTSThe patient with IKZF1-haploinsufficiency exhibited notable B cell and T cell dysregulation, with nearly total absence of regulatory B cells (Bregs) and increased percentage of naive CD4+ T cells. Pseudotime analysis in this patient suggested simplified B cell differentiation trajectories with arrested maturation and naïve-like cell resurgence. WGCNA identified a lupus-linked gene module (IKZF1, DUSP1, JUN, FOS), with inferred networks suggesting compensatory stress circuits (DUSP1, DDX17). Over-activation of IFN-JAK-STAT signaling pathway was observed in the patient with IKZF1-haploinsufficiency. Given persistent thrombocytopenia, baricitinib combined with mycophenolate mofetil was administered based on these findings. Her platelet count returned to normal in a month after combination therapy with baricitinib.CONCLUSIONIKZF1 haploinsufficiency disrupted lymphocyte homeostasis, especially Bregs and naive CD4+ T cells, highlighting these as key IKZF1-functional targets. A phenotype- and single-cell-based approach may offer a pathway toward more precise diagnosis and personalized treatment strategies for monogenic lupus.
{"title":"Single-cell RNA sequencing informs precision targeting of monogenic lupus associated with IKZF1 haploinsufficiency.","authors":"Qi Zheng,Yejun Tan,Zhaoling Wang,Yanjie Qian,Qian Ma,Danping Shen,Meiping Lu","doi":"10.1002/art.70017","DOIUrl":"https://doi.org/10.1002/art.70017","url":null,"abstract":"OBJECTIVEThis study aimed to investigate the mechanisms of immune dysregulation in a pediatric patient with monogenic lupus driven by IKZF1-haploinsufficiency.METHODSPeripheral immune cells from patient with IKZF1-haploinsufficiency, lupus cases with no currently known genetic mutations, and healthy controls were analyzed using single-cell RNA sequencing. Bioinformatic analyses, including pseudotime trajectory and network reconstruction were performed. Activation of type I interferon (IFN) pathway was evaluated by measuring serum cytokine levels, IFN signatures, and the phosphorylation status of Janus kinase (JAK) and signal transducer and activator of transcription (STAT).RESULTSThe patient with IKZF1-haploinsufficiency exhibited notable B cell and T cell dysregulation, with nearly total absence of regulatory B cells (Bregs) and increased percentage of naive CD4+ T cells. Pseudotime analysis in this patient suggested simplified B cell differentiation trajectories with arrested maturation and naïve-like cell resurgence. WGCNA identified a lupus-linked gene module (IKZF1, DUSP1, JUN, FOS), with inferred networks suggesting compensatory stress circuits (DUSP1, DDX17). Over-activation of IFN-JAK-STAT signaling pathway was observed in the patient with IKZF1-haploinsufficiency. Given persistent thrombocytopenia, baricitinib combined with mycophenolate mofetil was administered based on these findings. Her platelet count returned to normal in a month after combination therapy with baricitinib.CONCLUSIONIKZF1 haploinsufficiency disrupted lymphocyte homeostasis, especially Bregs and naive CD4+ T cells, highlighting these as key IKZF1-functional targets. A phenotype- and single-cell-based approach may offer a pathway toward more precise diagnosis and personalized treatment strategies for monogenic lupus.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752722","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":"Refining the Interpretation of Drug Survival and Safety in VEXAS Syndrome: The Importance of Competing Risks and Exposure Time","authors":"Yi Pei, Runze Jiang, Shenglong Li","doi":"10.1002/art.70012","DOIUrl":"https://doi.org/10.1002/art.70012","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"26 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704241","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}
Dafne Capelusnik, Tali Eviatar, Corrado Campochiaro, Iftach Sagy, Arsene Mekinian
{"title":"Response to “Refining the Interpretation of Drug Survival and Safety in VEXAS Syndrome: The Importance of Competing Risks and Exposure Time” by Pei Y. et al. and “Reinterpreting the Efficacy of IL ‐1 Inhibitors in VEXAS Syndrome: A Matter of Superiority or Sequencing?” by Ding Z. et al","authors":"Dafne Capelusnik, Tali Eviatar, Corrado Campochiaro, Iftach Sagy, Arsene Mekinian","doi":"10.1002/art.70011","DOIUrl":"https://doi.org/10.1002/art.70011","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"3 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704240","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}
Amber De Visscher,Jarne Beliën,Bert Malengier-Devlies,Eline Bernaerts,Leana De Vuyst,Jessica Filtjens,Kourosh Ahmadzadeh,Tania Mitera,Nele Berghmans,Katerina Laskari,Yvan Jamilloux,Paul Regnier,David Saadoun,Charlotte Girard-Guyonvarc'h,Cem Gabay,Mieke Gouwy,Paul Proost,Stephanie Humblet-Baron,Yvonne M Mueller,Stefan J Erkland,Harmen J G van de Werken,Dwin G B Grashof,Peter D Katsikis,Immunome Project Consortium, ,Carine Wouters,Carine Wouters,Patrick Matthys
OBJECTIVEStill's disease (SD) is a rare systemic inflammatory disorder of unknown origin, characterized by episodes of uncontrolled inflammation. While natural killer (NK) cells have been implicated in SD pathogenesis, their precise role remains elusive.METHODSWithin the framework of the ImmunAID consortium, we performed a comprehensive NK cell phenotyping in an international cohort comprising 121 patients with distinct systemic autoinflammatory diseases (53 SD, 23 chronic recurrent multifocal osteomyelitis, 23 Familial Mediterranean fever, and 22 inflammation of unknown origin) and 32 healthy controls.RESULTSOur analysis revealed a unique NK cell signature in SD, characterized by a reduction in NK cell frequency and elevated Fas expression, rendering them more susceptible to in vitro Fas ligand-induced apoptosis. Fas ligand was expressed by SD monocytes and CD38+HLA-DR+ cycling lymphocytes. SD NK cells displayed a hyperactivated but exhausted phenotype, including cytokine unresponsiveness, all features not observed in the other groups. This NK cell dysfunctional profile normalized during clinical remission. Exposure of healthy NK cells to IL-12, IL-15 and IL-18 recapitulates the SD-associated phenotype, suggesting an inflammation-driven mechanism. Transcriptomic profiling identified microRNA miR-146a as a potential regulator of this NK cell dysfunction.CONCLUSIONOur findings establish NK cell apoptosis, exhaustion, and cytokine unresponsiveness as defining immunological features of SD, distinguishing it from other inflammatory diseases in this cohort. This dysfunctional NK cell state may underlie the heightened risk of macrophage activation syndrome in SD and highlights inflammatory cytokines and miR-146a as promising therapeutic targets to mitigate disease severity and prevent life-threatening complications.
{"title":"Distinct natural killer cell signature in still's disease: Insights from a multinational immunome project consortium for autoinflammatory disorders.","authors":"Amber De Visscher,Jarne Beliën,Bert Malengier-Devlies,Eline Bernaerts,Leana De Vuyst,Jessica Filtjens,Kourosh Ahmadzadeh,Tania Mitera,Nele Berghmans,Katerina Laskari,Yvan Jamilloux,Paul Regnier,David Saadoun,Charlotte Girard-Guyonvarc'h,Cem Gabay,Mieke Gouwy,Paul Proost,Stephanie Humblet-Baron,Yvonne M Mueller,Stefan J Erkland,Harmen J G van de Werken,Dwin G B Grashof,Peter D Katsikis,Immunome Project Consortium, ,Carine Wouters,Carine Wouters,Patrick Matthys","doi":"10.1002/art.70008","DOIUrl":"https://doi.org/10.1002/art.70008","url":null,"abstract":"OBJECTIVEStill's disease (SD) is a rare systemic inflammatory disorder of unknown origin, characterized by episodes of uncontrolled inflammation. While natural killer (NK) cells have been implicated in SD pathogenesis, their precise role remains elusive.METHODSWithin the framework of the ImmunAID consortium, we performed a comprehensive NK cell phenotyping in an international cohort comprising 121 patients with distinct systemic autoinflammatory diseases (53 SD, 23 chronic recurrent multifocal osteomyelitis, 23 Familial Mediterranean fever, and 22 inflammation of unknown origin) and 32 healthy controls.RESULTSOur analysis revealed a unique NK cell signature in SD, characterized by a reduction in NK cell frequency and elevated Fas expression, rendering them more susceptible to in vitro Fas ligand-induced apoptosis. Fas ligand was expressed by SD monocytes and CD38+HLA-DR+ cycling lymphocytes. SD NK cells displayed a hyperactivated but exhausted phenotype, including cytokine unresponsiveness, all features not observed in the other groups. This NK cell dysfunctional profile normalized during clinical remission. Exposure of healthy NK cells to IL-12, IL-15 and IL-18 recapitulates the SD-associated phenotype, suggesting an inflammation-driven mechanism. Transcriptomic profiling identified microRNA miR-146a as a potential regulator of this NK cell dysfunction.CONCLUSIONOur findings establish NK cell apoptosis, exhaustion, and cytokine unresponsiveness as defining immunological features of SD, distinguishing it from other inflammatory diseases in this cohort. This dysfunctional NK cell state may underlie the heightened risk of macrophage activation syndrome in SD and highlights inflammatory cytokines and miR-146a as promising therapeutic targets to mitigate disease severity and prevent life-threatening complications.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704423","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}
Shivani Garg,Benoît Blanchet,Yann Nguyen,Fauzia Hollnagel,Ada Clarke,Michelle Petri,Murray B Urowitz,John G Hanly,Caroline Gordon,Sang-Cheol Bae,Juanita Romero-Diaz,Jorge Sanchez-Guerrero,Ann E Clarke,Sasha Bernatsky,Daniel J Wallace,David A Isenberg,Anisur Rahman,Joan T Merrill,Paul R Fortin,Dafna D Gladman,Ian N Bruce,Ellen M Ginzler,Mary Anne Dooley,Rosalind Ramsey-Goldman,Susan Manzi,Andreas Jönsen,Graciela S Alarcón,Ronald F Van Vollenhoven,Cynthia Aranow,Véronique Le Guern,Meggan Mackay,Guillermo Ruiz-Irastorza,S Sam Lim,Murat Inanc,Kenneth C Kalunian,Søren Jacobsen,Christine A Peschken,Diane L Kamen,Anca Askanase,Jill Buyon,Julie Chezel,Alicja Puszkiel,Nathalie Costedoat-Chalumeau
BACKGROUNDUsing hydroxychloroquine (HCQ) dose of 5 mg/kg/day in systemic lupus erythematosus (SLE) is associated with a higher risk of flares; HCQ blood level monitoring could be a better way to adjust HCQ dose. We studied the upper threshold for a reference range of HCQ levels to inform routine monitoring.METHODSThis observational study included patients (n=2010) across the Systemic Lupus International Collaborating Clinics (SLICC), Wisconsin, International, and French studies, who underwent HCQ blood level measurements. Using adjusted spline and logistic regression analyses on the cross-sectional data, we first identified a HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for SLE Disease Activity Index 2000 (SLEDAI-2K ≥6). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels.RESULTSAmong 1842 patients (excluding 168 patients with very low HCQ blood levels), 4.9% had HCQ related toxicity. Odds of toxicity were 2.1-fold higher with blood levels ≥1150 ng/mL, and 1.7-fold higher with cumulative HCQ dose per 1000g increase. Blood levels ≥1150 ng/mL were associated with a saturation in therapeutic effect, indicating supratherapeutic levels. Patients with CKD stage ≥3 had 2.3-fold higher odds of having supratherapeutic levels (≥1150 ng/mL).CONCLUSIONThe therapeutic reference range for HCQ blood level monitoring is 750-<1150 ng/ml. HCQ level monitoring could optimize HCQ use, particularly in patients with CKD stage ≥3. Future longitudinal studies are needed to validate the use of HCQ blood level monitoring in optimizing dosing.
{"title":"Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring.","authors":"Shivani Garg,Benoît Blanchet,Yann Nguyen,Fauzia Hollnagel,Ada Clarke,Michelle Petri,Murray B Urowitz,John G Hanly,Caroline Gordon,Sang-Cheol Bae,Juanita Romero-Diaz,Jorge Sanchez-Guerrero,Ann E Clarke,Sasha Bernatsky,Daniel J Wallace,David A Isenberg,Anisur Rahman,Joan T Merrill,Paul R Fortin,Dafna D Gladman,Ian N Bruce,Ellen M Ginzler,Mary Anne Dooley,Rosalind Ramsey-Goldman,Susan Manzi,Andreas Jönsen,Graciela S Alarcón,Ronald F Van Vollenhoven,Cynthia Aranow,Véronique Le Guern,Meggan Mackay,Guillermo Ruiz-Irastorza,S Sam Lim,Murat Inanc,Kenneth C Kalunian,Søren Jacobsen,Christine A Peschken,Diane L Kamen,Anca Askanase,Jill Buyon,Julie Chezel,Alicja Puszkiel,Nathalie Costedoat-Chalumeau","doi":"10.1002/art.70010","DOIUrl":"https://doi.org/10.1002/art.70010","url":null,"abstract":"BACKGROUNDUsing hydroxychloroquine (HCQ) dose of 5 mg/kg/day in systemic lupus erythematosus (SLE) is associated with a higher risk of flares; HCQ blood level monitoring could be a better way to adjust HCQ dose. We studied the upper threshold for a reference range of HCQ levels to inform routine monitoring.METHODSThis observational study included patients (n=2010) across the Systemic Lupus International Collaborating Clinics (SLICC), Wisconsin, International, and French studies, who underwent HCQ blood level measurements. Using adjusted spline and logistic regression analyses on the cross-sectional data, we first identified a HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for SLE Disease Activity Index 2000 (SLEDAI-2K ≥6). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels.RESULTSAmong 1842 patients (excluding 168 patients with very low HCQ blood levels), 4.9% had HCQ related toxicity. Odds of toxicity were 2.1-fold higher with blood levels ≥1150 ng/mL, and 1.7-fold higher with cumulative HCQ dose per 1000g increase. Blood levels ≥1150 ng/mL were associated with a saturation in therapeutic effect, indicating supratherapeutic levels. Patients with CKD stage ≥3 had 2.3-fold higher odds of having supratherapeutic levels (≥1150 ng/mL).CONCLUSIONThe therapeutic reference range for HCQ blood level monitoring is 750-<1150 ng/ml. HCQ level monitoring could optimize HCQ use, particularly in patients with CKD stage ≥3. Future longitudinal studies are needed to validate the use of HCQ blood level monitoring in optimizing dosing.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"13 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710927","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}
For a searchable version of these abstracts, please visit www.acrabstracts.org.
有关这些摘要的可搜索版本，请访问www.acrabstracts.org。
{"title":"Abstract Supplement ACR Convergence 2025","authors":"","doi":"10.1002/art.43421","DOIUrl":"https://doi.org/10.1002/art.43421","url":null,"abstract":"<p>For a searchable version of these abstracts, please visit www.acrabstracts.org.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 S9","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acrjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/art.43421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For a searchable version of these abstracts, please visit www.acrabstracts.org.
有关这些摘要的可搜索版本，请访问www.acrabstracts.org。
{"title":"Abstract Supplement ACR Convergence 2025","authors":"","doi":"10.1002/art.43421","DOIUrl":"https://doi.org/10.1002/art.43421","url":null,"abstract":"<p>For a searchable version of these abstracts, please visit www.acrabstracts.org.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 S9","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acrjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/art.43421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-15DOI: 10.1002/art.43272
Carol A Langford, Nader Khalidi, Jason Springer, Marcia Friedman, Bernhard Hellmich, Christian Pagnoux, Natasha Dehghan, Ora Gewurz-Singer, Curry L Koening, Yih Chang Lin, Paul A Monach, Larry W Moreland, Aurore Fifi-Mah, Oliver Flossmann, Lindsy J Forbess, Peter Lanyon, Eamonn Molloy, Ulrich Specks, Robert Spiera, Elaine Yacyshyn, Carol A McAlear, Cristina Burroughs, Rachel B Jones, Rennie L Rhee, Rula Hajj-Ali, Kenneth J Warrington, David Cuthbertson, Jeffrey P Krischer, David Jayne, Peter A Merkel
Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA).
Methods: In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open-label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months.
Results: Sixty-five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo (P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality-of-life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection.
Conclusion: In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.
{"title":"A Randomized, Double-Blind, Placebo-Controlled Trial of Abatacept for the Treatment of Relapsing, Nonsevere Granulomatosis With Polyangiitis.","authors":"Carol A Langford, Nader Khalidi, Jason Springer, Marcia Friedman, Bernhard Hellmich, Christian Pagnoux, Natasha Dehghan, Ora Gewurz-Singer, Curry L Koening, Yih Chang Lin, Paul A Monach, Larry W Moreland, Aurore Fifi-Mah, Oliver Flossmann, Lindsy J Forbess, Peter Lanyon, Eamonn Molloy, Ulrich Specks, Robert Spiera, Elaine Yacyshyn, Carol A McAlear, Cristina Burroughs, Rachel B Jones, Rennie L Rhee, Rula Hajj-Ali, Kenneth J Warrington, David Cuthbertson, Jeffrey P Krischer, David Jayne, Peter A Merkel","doi":"10.1002/art.43272","DOIUrl":"10.1002/art.43272","url":null,"abstract":"<p><strong>Objective: </strong>To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA).</p><p><strong>Methods: </strong>In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open-label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months.</p><p><strong>Results: </strong>Sixty-five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo (P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality-of-life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection.</p><p><strong>Conclusion: </strong>In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"1739-1748"},"PeriodicalIF":10.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruna de Moraes Mazetto Fonseca, Somanathapura K. NaveenKumar, Srilakshmi Yalavarthi, Kavya Sugur, Thalia G. Newman, Claire K. Hoy, Cyrus Sarosh, Jordan K. Schaefer, Ajay Tambralli, Jacqueline A. Madison, Yu Zuo, Fernanda Orsi, Michael Holinstat, Jason S. Knight
ATP is released from platelets through both degranulation and pannexin-1 (PANX1) channels. ATP then activates P2X receptors to amplify platelet activation via calcium-dependent signaling.
{"title":"Prothrombotic Activation of Platelet Pannexin 1 Channels in Antiphospholipid Syndrome","authors":"Bruna de Moraes Mazetto Fonseca, Somanathapura K. NaveenKumar, Srilakshmi Yalavarthi, Kavya Sugur, Thalia G. Newman, Claire K. Hoy, Cyrus Sarosh, Jordan K. Schaefer, Ajay Tambralli, Jacqueline A. Madison, Yu Zuo, Fernanda Orsi, Michael Holinstat, Jason S. Knight","doi":"10.1002/art.70001","DOIUrl":"https://doi.org/10.1002/art.70001","url":null,"abstract":"ATP is released from platelets through both degranulation and pannexin-1 (PANX1) channels. ATP then activates P2X receptors to amplify platelet activation via calcium-dependent signaling.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"39 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651593","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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