Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX

被引：31

作者：

Hadjadj, Jerome ^{[1
]}

Yann Nguyen ^{[2
]}

Mouloudj, Dalila ^{[1
]}

Bourguiba, Rim ^{[3
,4
]}

Heiblig, Mael ^{[5
]}

Aloui, Hassina ^{[3
]}

McAvoy, Chloe ^{[1
]}

Lacombe, Valentin ^{[6
]}

Ardois, Samuel ^{[7
]}

Campochiaro, Corrado ^{[8
]}

Maria, Alexandre ^{[9
]}

Coustal, Cyrille ^{[9
]}

Comont, Thibault ^{[10
]}

Lazaro, Estibaliz ^{[11
]}

Lifermann, Francois ^{[12
]}

Le Guenno, Guillaume ^{[13
]}

Lobbes, Herve ^{[13
]}

Grobost, Vincent ^{[13
]}

Outh, Roderau ^{[14
]}

Campagne, Julien ^{[15
]}

Dor-Etienne, Anais ^{[15
]}

Garnier, Alice ^{[16
]}

Jamilloux, Yvan ^{[17
]}

Dossier, Antoine ^{[18
]}

Samson, Maxime ^{[19
,20
]}

Audia, Sylvain ^{[19
,20
]}

Nicolas, Barbara ^{[19
,20
]}

Mathian, Alexis ^{[21
]}

de Maleprade, Baptiste ^{[22
]}

De Sainte-Marie, Benjamin ^{[23
]}

Faucher, Benoit ^{[23
]}

Bouaziz, Jean-David ^{[24
]}

Broner, Jonathan ^{[25
]}

Dumain, Cyril ^{[25
]}

Antoine, Carole ^{[26
]}

Carpentier, Benjamin ^{[27
]}

Castel, Brice ^{[28
]}

Lartigau-Roussin, Celine ^{[29
]}

Crickx, Etienne ^{[30
]}

Volle, Geoffroy ^{[30
]}

Fayard, Damien ^{[31
]}

Decker, Paul ^{[32
]}

Moulinet, Thomas ^{[32
]}

Dumont, Anael ^{[33
]}

Nguyen, Alexandre ^{[33
]}

Aouba, Achille ^{[33
]}

Martellosio, Jean-Philippe ^{[34
]}

Levavasseur, Matthieu ^{[35
]}

Puigrenier, Sebastien ^{[36
]}

Antoine, Pascale ^{[36
]}

机构：

[1] Sorbonne Univ, Hop St Antoine, AP HP, Serv Med Interne, Paris, France

[2] Univ Paris Cite, Serv Med Interne, Hop Beaujon, AP HP Nord, Clichy, France

[3] Sorbonne Univ, Hosp Tenon, CEREMAIA, Med Interne, Paris, France

[4] Univ Tunis El Manar, Fac Med Tunis, Tunis, Tunisia

[5] Hop Lyon Sud HCL, Hematol, Pierre Benite, France

[6] Univ Hosp Ctr Angers, Dept Internal Med, Angers, Pays De La Loir, France

[7] CHU Rennes, Med Interne, Rennes, France

[8] Vita Salute Vita Salute San Raffaele Univ, IRCCS San Raffaele Hosp, Unit Immunol Rheumatol Allergy Ad Rre Dis, Milan, Italy

[9] Univ Montpellier, Montpellier Univ Hosp, Dept Internal Med Multiorgan Dis, St Eloi Hosp, Montpellier, France

[10] Univ Paul Sabatier, Serv Med Interne IUCT Oncopole, CHU Toulouse, Toulouse, France

[11] CHU Bordeaux, Internal Med, Bordeaux, Nouvelle Aquita, France

[12] Ctr Hosp Dax, Serv Med Interne, Dax, Nouvelle Aquita, France

[13] CHU Estaing, Med Interne, Clermont Ferrand, Auvergne Rhone, France

[14] Perpignan Univ, Serv Med Interne & Gen, Perpignan, France

[15] Hop Robert Schuman, Med Interne, Metz, France

[16] Nantes Univ Hosp, Hematol Dept, Nantes, France

[17] Univ Claude Bernard Lyon 1, Hop Univ Croix Rousse, Hosp Civils Lyon, Dept Internal Med, Lyon, France

[18] Hop Bichat Claude Bernard, AP HP, Serv Med Interne, Paris, France

[19] CHU Dijon Bourgogne, Serv Med Interne & Immunol Clin, Ctr Reference Constitutif Malad Autoimmunes & Aut, Dijon, France

[20] Univ Bourgogne Franche Comte, RIGHT Interact Greffon Hote Tumeur Ingn Cellulair, UMR1098, EFS BFC,INSERM, Dijon, France

[21] Hop Univ Pitie Salpetriere, French Natl Referral Ctr Syst Lupus Erythematosus, Serv Med Interne 2, Inst E3M,Inserm UMRS,Ctr Immunol & Malad Infect C, Paris, Ile De France, France

[22] CHU Rouen, Rhumatol, Rouen, Normandie, France

[23] Ctr Hosp Univ La Timone, Dept Internal Med, Marseille, France

[24] Hop St Louis, Dermatol, Paris, Ile De France, France

[25] Univ Hosp Ctr Nimes, Internal Med Dept, Nimes, France

[26] St Anne Mil Teaching Hosp, Internal Med, Toulon, Provence Alpes, France

[27] Univ Catholique Lille, Hop St Vincent de Paul, Hematol Clin, Lille, Hauts De France, France

[28] Ctr Hosp Lourdes, Serv Med Interne & Immunol Clin, Lourdes, France

[29] CH Ouest Reunion, Internal Med, St Paul, France

[30] Univ Paris Est Creteil, Federat Hosp Univ TRUE InnovaT theRapy ImmUne dis, Hop Henri Mondor, Assistance Publ Hop Paris AP HP,Ctr Natl Referenc, Creteil, France

[31] Univ Hosp Ctr Gabriel Montpied, Clermont Ferrand, Auvergne Rhone, France

[32] Univ Lorraine, CNRS, IMoPA, CHU Nancy,UMR 7365,Med Interne & Immunol Clin, Nancy, France

[33] Univ Hosp Ctr Caen, Dept Internal Med, Caen, Basse Normandie, France

[34] Ctr Hosp Univ Poitiers, Dept Internal Med, Poitiers, France

[35] Ctr Hosp Genevois, Dermatol, Annecy, France

[36] Ctr Hosp Boulogne Sur Mer, Dept Internal Med, Boulogne Sur Mer, France

[37] Tarbes Hosp, Internal Med Unit, Tarbes, France

[38] Hop Necker Enfants Malad, Hematol, Paris, France

[39] Archet 1 Hosp, Univ Hosp Nice, Internal Med Dept, Nice, France

[40] Amiens Univ Hosp, Dept Internal Med, Amiens, France

[41] Sorbonne Univ, Fac Med, Serv Dermatol & Allergol, AP HP, Paris, France

[42] Hop Univ Strasbourg, Natl Reference Ctr Rare Dis RESO, Dept Rheumatol, Strasbourg, France

[43] INSERM UMR S 1109, Strasbourg, France

[44] Reims Champagne Ardenne Univ, Serv Med Interne Malad Infect Immunol Clin, Reims, France

[45] Univ Hosp Martinique, Serv Med Interne, Fort De France, Martinique, France

[46] Fdn Adolphe de Rothschild Hosp, Internal Med, Paris, France

[47] CHD Vendee, Serv Med Interne, La Roche Sur Yon, France

[48] Pierre Oudot Hosp Bourgoin Jallieu, Serv Med Interne, Bourgoin Jallieu, France

[49] Hop Univ Strasbourg, Serv Immunol Clin & Med Interne, Strasbourg, France

[50] Hosp Civils Lyon, Serv Hematol Biol, Hop Lyon Sud, Pierre Benite, France

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2024年 / 83卷 / 10期

关键词：

Biological Therapy; Inflammation; Tumor Necrosis Factor Inhibitors; DISEASE;

D O I：

10.1136/ard-2024-225640

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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) <= 10mg/L and a <= 10mg/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 (TNF alpha) blockers and 12 (6%) other targeted therapies. At 3months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNF alpha blockers or other targeted therapies. At 6months, 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.

引用

页码：1358 / 1367

页数：10

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