Jerome Hadjadj, Yann Nguyen, Dalila Mouloudj, Rim Bourguiba, Mael Heiblig, Hassina Aloui, Chloe McAvoy, Valentin Lacombe, Samuel Ardois, Corrado Campochiaro, Alexandre Maria, Cyrille Coustal, Thibault Comont, Estibaliz Lazaro, Francois Lifermann, Guillaume Le Guenno, Hervé Lobbes, Vincent Grobost, Roderau Outh, Julien Campagne, Anais Dor-Etienne, Alice Garnier, Yvan Jamilloux, Antoine Dossier, Maxime Samson, Sylvain Audia, Barbara Nicolas, Alexis Mathian, Baptiste de Maleprade, Benjamin De Sainte-Marie, Benoit Faucher, Jean-David Bouaziz, Jonathan Broner, Cyril Dumain, Carole Antoine, Benjamin Carpentier, Brice Castel, Celine Lartigau-Roussin, Etienne Crickx, Geoffroy Volle, Damien Fayard, Paul Decker, Thomas Moulinet, Anael Dumont, Alexandre Nguyen, Achille Aouba, Jean-Philippe Martellosio, Matthieu Levavasseur, Sebastien Puigrenier, Pascale Antoine, Jean-Thomas Giraud, Olivier Hermine, Carole Lacout, Nihal Martis, Jean-Denis Karam, Francois Chasset, Laurent Arnaud, Paola Marianetti, Christophe Deligny, Thibaud Chazal, Pascal Woaye-Hune, Murielle Roux-Sauvat, Aurore Meyer, Pierre Sujobert, Pierre Hirsch, Noemie Abisror, Pierre Fenaux, Olivier Kosmider, Vincent Jachiet, Olivier Fain, Benjamin Terrier, Arsène Mekinian, Sophie Georgin-Lavialle
{"title":"Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.","authors":"Jerome Hadjadj, Yann Nguyen, Dalila Mouloudj, Rim Bourguiba, Mael Heiblig, Hassina Aloui, Chloe McAvoy, Valentin Lacombe, Samuel Ardois, Corrado Campochiaro, Alexandre Maria, Cyrille Coustal, Thibault Comont, Estibaliz Lazaro, Francois Lifermann, Guillaume Le Guenno, Hervé Lobbes, Vincent Grobost, Roderau Outh, Julien Campagne, Anais Dor-Etienne, Alice Garnier, Yvan Jamilloux, Antoine Dossier, Maxime Samson, Sylvain Audia, Barbara Nicolas, Alexis Mathian, Baptiste de Maleprade, Benjamin De Sainte-Marie, Benoit Faucher, Jean-David Bouaziz, Jonathan Broner, Cyril Dumain, Carole Antoine, Benjamin Carpentier, Brice Castel, Celine Lartigau-Roussin, Etienne Crickx, Geoffroy Volle, Damien Fayard, Paul Decker, Thomas Moulinet, Anael Dumont, Alexandre Nguyen, Achille Aouba, Jean-Philippe Martellosio, Matthieu Levavasseur, Sebastien Puigrenier, Pascale Antoine, Jean-Thomas Giraud, Olivier Hermine, Carole Lacout, Nihal Martis, Jean-Denis Karam, Francois Chasset, Laurent Arnaud, Paola Marianetti, Christophe Deligny, Thibaud Chazal, Pascal Woaye-Hune, Murielle Roux-Sauvat, Aurore Meyer, Pierre Sujobert, Pierre Hirsch, Noemie Abisror, Pierre Fenaux, Olivier Kosmider, Vincent Jachiet, Olivier Fain, Benjamin Terrier, Arsène Mekinian, Sophie Georgin-Lavialle","doi":"10.1136/ard-2024-225640","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.</p><p><strong>Methods: </strong>Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose.</p><p><strong>Results: </strong>110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors.</p><p><strong>Conclusions: </strong>This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/ard-2024-225640","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.
Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose.
Results: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors.
Conclusions: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.
期刊介绍:
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.