RMD Open (Apr 2023)
Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study
- Patrice Cacoub,
- Arsène Mekinian,
- David Saadoun,
- Pavel I Novikov,
- Savino Sciascia,
- Corrado Campochiaro,
- Olivier Fain,
- Ilya Smitienko,
- Nicolas Schleinitz,
- Patrick Jégo,
- Francesco Muratore,
- Carlo Salvarani,
- Elena Galli,
- Sabine Berthier,
- Marc Lambert,
- François Maurier,
- Isabelle Kone-Paut,
- Sergey Moiseev,
- Masataka Kuwana,
- Alexandre Belot,
- Martin Michaud,
- Francis Gaches,
- Achille Aouba,
- Xavier Puechal,
- Karim Sacre,
- Tiphaine Goulenok,
- Alessandro Tomelleri,
- Thomas Sené,
- Elena Marina Baldissera,
- Luigi Boiardi,
- Abid Awisat,
- Ygal Benhamou,
- Vahan Mukuchyan,
- Mathieu Vautier,
- Azeddine Dellal,
- Lucie Biard,
- Julie Seguier,
- José Hernández-Rodríguez,
- Olivier Espitia,
- Sebastien Humbert,
- Guillaume Denis,
- Nolan Hassold,
- Dagna Lorenzo,
- Helene Munoz Pons,
- Jean Baptiste Gaultier,
- Le Mouel Edwige,
- Antoinette Perlat,
- Bertrand Lioger,
- Jonathan Broner,
- Virginie Dufrost,
- Faten Frikha,
- Alexandra Audemard-Verger,
- Pascal Woaye-Hune,
- Pierre Zeminsky,
- Moya Alvarado,
- Matheus Vieira,
- Alberto Lo Gullo
Affiliations
- Patrice Cacoub
- AP-HP, Hôpital Pitié Salpetrière, Department of Internal Medicine and Clinical Immunology France, Centre national de référence maladies Autoimmunes Systémiques rares, Centre national de référence maladies Autoinflammatoires et Amylose, and Inflammation-Immunopathology-Biotherapy Department (DMU i3), Sorbonne Universités, Paris, France
- Arsène Mekinian
- Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service de médecine interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), F-75012, Paris, France, French Armenian research center, Erevan, Armenia
- David Saadoun
- AP-HP, Hôpital Pitié Salpetrière, Department of Internal Medicine and Clinical Immunology France, Centre national de référence maladies Autoimmunes Systémiques rares, Centre national de référence maladies Autoinflammatoires et Amylose, and Inflammation-Immunopathology-Biotherapy Department (DMU i3), Sorbonne Universités, Paris, France
- Pavel I Novikov
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russian Federation
- Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Aosta Valley Network for Rare Diseases, Nephrology and Dialysis, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy
- Olivier Fain
- Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service de médecine interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), F-75012, Paris, France, French Armenian research center, Erevan, Armenia
- Ilya Smitienko
- Rheumatology Department, Medical Center K-31, Moscow, Russian Federation
- Nicolas Schleinitz
- Département de médecine interne, CHU de La Timone, Marseille, France
- Patrick Jégo
- Internal Medicine and Clinical Immunology Department, CHU Rennes, Universitaire de Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France
- Francesco Muratore
- Unit of Rheumatology, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
- Carlo Salvarani
- Azienda USL-IRCCS; Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Italy
- Elena Galli
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- Sabine Berthier
- Service de médecine interne et immunologie clinique, Université Dijon, Hôpital Dijon, Dijon, France
- Marc Lambert
- Univ. Lille, CHU Lille, Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), INSERM, UMR 1167, RID-AGE, Lille, France
- François Maurier
- Service de Médecine Interne et Immunologie Clinique Groupe Hospitalier UNEOS, Vantoux, France
- Isabelle Kone-Paut
- 17 Department of Paediatric Rheumatology and CEREMAIA, Hôpital Bicêtre, AP HP, Université Paris Saclay, Paris, France
- Sergey Moiseev
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russian Federation
- Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
- Alexandre Belot
- International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, Lyon, France
- Martin Michaud
- Médecine Interne, Hôpital Joseph Ducuing, Toulouse, France
- Francis Gaches
- Médecine Interne, Hôpital Joseph Ducuing, Toulouse, France
- Achille Aouba
- Département de médecine interne, CHU Caen, Caen, France
- Xavier Puechal
- Université Paris Descartes, Paris, France ; AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Service de médecine interne, 27 rue du Faubourg Saint-Jacques, Paris, France
- Karim Sacre
- Département de Médecine Interne, Hôpital Bichat, Université de Paris, Assistance Publique Hôpitaux de Paris, INSERM U1149, Paris, France
- Tiphaine Goulenok
- Département de Médecine Interne, Hôpital Bichat, Université de Paris, Assistance Publique Hôpitaux de Paris, INSERM U1149, Paris, France
- Alessandro Tomelleri
- 1 Unit of Immunology, Rheumatology, Allergy and Rare diseases, San Raffaele Hospital, Milano, Lombardia, Italy
- Thomas Sené
- Service de médecine interne, Rothschild, Paris, France
- Elena Marina Baldissera
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- Luigi Boiardi
- Azienda USL-IRCCS; Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Italy
- Abid Awisat
- Rheumatology Unit, Bnei Zion Hospital, Haifa, Israel
- Ygal Benhamou
- Service de médecine interne, Université Rouen, CHU de Rouen, Rouen, France
- Vahan Mukuchyan
- Department of Internal Medicine and Rheumatology, Nairi hospital, Erevan, Armenia
- Mathieu Vautier
- Université de Paris, AP-HP, Hôpital Saint Louis, Service de Biostatistique et Information Médicale (DMU PRISME), INSERM U1153 Team ECSTRRA, Paris, France
- Azeddine Dellal
- Service de rhumatologie, Hôpital Montfermeil, GHI Le Raincy Montfermeil, Montfermeil, France
- Lucie Biard
- Université de Paris, AP-HP, Hôpital Saint Louis, Service de Biostatistique et Information Médicale (DMU PRISME), INSERM U1153 Team ECSTRRA, Paris, France
- Julie Seguier
- Département de médecine interne, CHU de La Timone, Marseille, France
- José Hernández-Rodríguez
- Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Olivier Espitia
- Department of internal and vascular medicine, Nantes Université, CHU Nantes, F-44000 Nantes, France
- Sebastien Humbert
- Service de médecine interne et immunologie clinique, Hôpital Besancon, Besancon, France
- Guillaume Denis
- Centre Hospitalier de Rochefort, Rochefort, Nouvelle-Aquitaine, France
- Nolan Hassold
- Service de Rhumatologie pédiatrique et centre de référence des maladies autoinflammatoires et de l`amylose inflammatoire, CEREMAIA, hôpital de Bicêtre, APHP, France, université de Paris Sud-Saclay, Paris, France
- Dagna Lorenzo
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- Helene Munoz Pons
- Département de médecine interne, CHU Saint Etienne, Saint-Etienne, France
- Jean Baptiste Gaultier
- Service de Médecine Interne, Hôpital Nord, Centre Hospitalier universitaire de St Etienne, Saint Etienne, France
- Le Mouel Edwige
- Internal Medicine and Clinical Immunology Department, CHU Rennes, Universitaire de Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France
- Antoinette Perlat
- Internal Medicine and Clinical Immunology Department, CHU Rennes, Universitaire de Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France
- Bertrand Lioger
- Service de médecine interne, CHU de Blois, Blois, France
- Jonathan Broner
- Service de médecine interne, CHU de Nimes, Nimes, France
- Virginie Dufrost
- Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, University of Lorraine, Inserm UMR_S 1116, CHRU de Nancy, Nancy, France
- Faten Frikha
- Service de Médecine interne CHU Hédi Chaker, Route El Ain 3029 Sfax -Faculté de Médecine de Sfax, Sfax, Tunisia
- Alexandra Audemard-Verger
- Department of Internal Medicine and Clinical Immunology, CHRU Tours, University of Tours, Tours, France
- Pascal Woaye-Hune
- Service de médecine interne, Hôpital de la Réunion, Réunion, France
- Pierre Zeminsky
- Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, University of Lorraine, Inserm UMR_S 1116, CHRU de Nancy, Nancy, France
- Moya Alvarado
- Azienda USL-IRCCS; Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Italy
- Matheus Vieira
- AP-HP, Hôpital Pitié Salpetrière, Department of Internal Medicine and Clinical Immunology France, Centre national de référence maladies Autoimmunes Systémiques rares, Centre national de référence maladies Autoinflammatoires et Amylose, and Inflammation-Immunopathology-Biotherapy Department (DMU i3), Sorbonne Universités, Paris, France
- Alberto Lo Gullo
- Unit of Rheumatology, Department of Medicine, ARNAS Garibaldi Hospital, Catania, Italy
- DOI
- https://doi.org/10.1136/rmdopen-2022-002830
- Journal volume & issue
-
Vol. 9,
no. 2
Abstract
Objectives In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients.Methods We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.Results A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab.Conclusion In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months.
