Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX. (2024)

Afiliação

• Hadjadj J; Sorbonne Université, service de médecine interne, Hôpital Saint-Antoine, AP-HP, Paris, France jerome.hadjadj@aphp.fr sophie.georgin-lavialle@aphp.fr.
• Nguyen Y; Service de médecine interne, Hôpital Beaujon, AP-HP.Nord, Université Paris Cité, Clichy, France.
• Mouloudj D; Sorbonne Université, service de médecine interne, Hôpital Saint-Antoine, AP-HP, Paris, France.
• Bourguiba R; Médecine Interne, CEREMAIA, Sorbonne Université, Hospital Tenon, Paris, France.
• Heiblig M; Université Tunis el Manar, Faculté de médecine de Tunis, Tunis, Tunisia.
• Aloui H; Hématologie, Hôpital Lyon Sud - HCL, Pierre-Bénite, France.
• McAvoy C; Médecine Interne, CEREMAIA, Sorbonne Université, Hospital Tenon, Paris, France.
• Lacombe V; Sorbonne Université, service de médecine interne, Hôpital Saint-Antoine, AP-HP, Paris, France.
• Ardois S; Department of Internal Medicine, University Hospital Centre Angers, Angers, Pays de la Loire, France.
• Campochiaro C; Médecine interne, CHU Rennes, Rennes, France.
• Maria A; Unit of Immunology, Rheumatology, Allergy ad Rre Disesaes. IRCCS San Raffaele Hospital. Vita-Salute Vita-Salute San Raffaele University, Milan, Italy.
• Coustal C; Department of Internal Medicine - Multi-organ Diseases, St Eloi Hospital, Montpellier University Hospital, Univ Montpellier, Montpellier, France.
• Comont T; Department of Internal Medicine - Multi-organ Diseases, St Eloi Hospital, Montpellier University Hospital, Univ Montpellier, Montpellier, France.
• Lazaro E; Service de médecine interne IUCT-Oncopole, CHU Toulouse, Université Paul Sabatier, Toulouse, France.
• Lifermann F; Internal Medicine, CHU de Bordeaux, Bordeaux, Nouvelle-Aquitaine, France.
• Le Guenno G; Service de médecine interne, Centre Hospitalier Dax, Dax, Nouvelle-Aquitaine, France.
• Lobbes H; Médecine Interne, CHU Estaing, Clermont-Ferrand, Auvergne-Rhône-Alpes, France.
• Grobost V; Médecine Interne, CHU Estaing, Clermont-Ferrand, Auvergne-Rhône-Alpes, France.
• Outh R; Médecine Interne, CHU Estaing, Clermont-Ferrand, Auvergne-Rhône-Alpes, France.
• Campagne J; Service de médecine interne et générale, Perpignan University, Perpignan, France.
• Dor-Etienne A; Médecine Interne, Hôpital Robert Schuman, Metz, France.
• Garnier A; Médecine Interne, Hôpital Robert Schuman, Metz, France.
• Jamilloux Y; Hematology Department, Nantes University Hospital, Nantes, France.
• Dossier A; Department of Internal Medicine, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, University Claude Bernard Lyon 1, Lyon, France.
• Samson M; Service de Médecine Interne, Hôpital Bichat-Claude-Bernard, APHP, Paris, France.
• Audia S; Service de Médecine Interne et Immunologie Clinique, Centre de Référence Constitutif des Maladies Auto-immunes et Auto-inflammatoires Rares de l'adulte, CHU Dijon-Bourgogne, Dijon,France; Université de Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénier
• Nicolas B; Service de Médecine Interne et Immunologie Clinique, Centre de Référence Constitutif des Maladies Auto-immunes et Auto-inflammatoires Rares de l'adulte, CHU Dijon-Bourgogne, Dijon,France; Université de Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénier
• Mathian A; Service de Médecine Interne et Immunologie Clinique, Centre de Référence Constitutif des Maladies Auto-immunes et Auto-inflammatoires Rares de l'adulte, CHU Dijon-Bourgogne, Dijon,France; Université de Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénier
• de Maleprade B; French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Universitaire Pitié Salpêtrière, Pari
• De Sainte-Marie B; Rhumatologie, CHU de Rouen, Rouen, Normandie, France.
• Faucher B; Department of Internal Medicine, Centre Hospitalier Universitaire de La Timone, Marseille, France.
• Bouaziz JD; Department of Internal Medicine, Centre Hospitalier Universitaire de La Timone, Marseille, France.
• Broner J; Dermatology, Hopital Saint-Louis, Paris, Île-de-France, France.
• Dumain C; Internal Medicine Department, University Hospital Centre Nimes, Nimes, France.
• Antoine C; Internal Medicine Department, University Hospital Centre Nimes, Nimes, France.
• Carpentier B; Internal Medicine, Sainte-Anne Military Teaching Hospital, Toulon, Provence-Alpes-Côte d'Azu, France.
• Castel B; Hématologie clinique, Universite Catholique de Lille Hopital Saint-Vincent de Paul, Lille, Hauts-de-France, France.
• Lartigau-Roussin C; Service de Médecine Interne et d'Immunologie clinique, Centre Hospitalier de Lourdes, Lourdes, France.
• Crickx E; Internal Medicine, CH Ouest Reunion, Saint Paul, France.
• Volle G; Centre national de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France.
• Fayard D; Centre national de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique Hôpitaux de Paris (AP-HP), Université Paris Est Créteil, Créteil, France.
• Decker P; University Hospital Centre Gabriel Montpied, Clermont-Ferrand, Auvergne-Rhône-Alpes, France.
• Moulinet T; Médecine interne et immunologie clinique, CHU de Nancy, UMR 7365, IMoPA, Université de Lorraine, CNRS, Nancy, France.
• Dumont A; Médecine interne et immunologie clinique, CHU de Nancy, UMR 7365, IMoPA, Université de Lorraine, CNRS, Nancy, France.
• Nguyen A; Department of Internal Medicine, University Hospital Centre Caen, Caen, Basse-Normandie, France.
• Aouba A; Department of Internal Medicine, University Hospital Centre Caen, Caen, Basse-Normandie, France.
• Martellosio JP; Department of Internal Medicine, University Hospital Centre Caen, Caen, Basse-Normandie, France.
• Levavasseur M; Department of Internal Medicine, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
• Puigrenier S; Dermatologie, Centre Hospitalier Genevois, Annecy, France.
• Antoine P; Department of Internal Medicine, Centre hospitalier de Boulogne-sur-Mer, Boulogne-sur-Mer, France.

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.