Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicentre retrospective study of 209 patients

Author:

Mekinian Arsène1ORCID,Biard Lucie2,Dagna Lorenzo34,Novikov Pavel5,Salvarani Carlo67,Espitia Olivier8,Sciascia Savino9ORCID,Michaud Martin10,Lambert Marc11,Hernández-Rodríguez José12ORCID,Schleinitz Nicolas13,Awisat Abid14,Puéchal Xavier15ORCID,Aouba Achille16,Munoz Pons Helene17,Smitienko Ilya18,Gaultier Jean Baptiste19,Le Mouel Edwige20,Benhamou Ygal21,Perlat Antoinette20,Jego Patrick20,Goulenok Tiphaine22ORCID,Sacre Karim22ORCID,Lioger Bertrand23,Hassold Nolan24,Broner Jonathan25ORCID,Dufrost Virginie26,Sene Thomas27ORCID,Seguier Julie13,Maurier Francois28,Berthier Sabine29,Belot Alexandre30ORCID,Frikha Faten31,Denis Guillaume32,Audemard-Verger Alexandra33ORCID,Kone Pault Isabelle24ORCID,Humbert Sebastien34,Woaye-Hune Pascal35,Tomelleri Alessandro3ORCID,Baldissera Elena3,Kuwana Masataka36ORCID,Lo Gullo Alberto37,Gaches Francis10,Zeminsky Pierre26,Galli Elena7,Alvarado Moya6,Boiardi Luigi6,Muratore Francesco6,Vautier Mathieu2,Campochiaro Corrado34ORCID,Moiseev Sergey5,Cacoub Patrice38,Fain Olivier1,Saadoun David38

Affiliation:

1. Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3)

2. Université de Paris, AP-HP, Hôpital Saint Louis, Service de Biostatistique et Information Médicale (DMU PRISME), INSERM U1153 Team ECSTRRA, Paris, France

3. Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital

4. Vita-Salute San Raffaele University, Milan, Italy

5. Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia

6. Unit of Rheumatology, Azienda USL-IRCCS di Reggio Emilia

7. Unit of Rheumatology, Università di Modena e Reggio Emilia, Italy

8. Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France

9. 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

10. Médecine Interne, Hôpital Joseph Ducuing, Toulouse

11. Service de Médecine Interne, CHU Lille, Université Lille II, Lille, France

12. Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

13. Département de Médecine Interne, CHU de La Timone, Marseille, France

14. Rheumatology Unit, Bnai Zion Medical Center, Haifa, Israel

15. AP-HP, Hôpital Cochin, Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Service de Médecine Interne, Université Paris Descartes, Paris

16. Département de Médecine Interne, CHU Caen, Caen

17. Département de Médecine Interne, CHU Saint Etienne, Saint Etienne, France

18. Rheumatology Department, Medical Center, Moscow, Russia

19. Service de Médecine Interne, Hôpital Nord, Centre Hospitalier Universitaire de St Etienne, Saint Etienne cedex 2

20. Département de Médecine Interne, CHU de Rennes, Rennes

21. Service de Médecine Interne, Université Rouen, CHU de Rouen, Rouen

22. Département de Médecine Interne, Hôpital Bichat, Université de Paris, Assistance Publique Hôpitaux de Paris, INSERM U1149, Paris

23. Service de Médecine Interne, CHU de Blois, Blois

24. Service de Rhumatologie Pédiatrique et Centre de Référence des Maladies Autoinflammatoires et de L'amylose Inflammatoire, CEREMAIA, Hôpital de Bicêtre, APHP, Université de Paris Sud-Saclay

25. Service de Médecine Interne, CHU de Nimes, Nimes

26. University of Lorraine, Inserm UMR_S 1116, CHRU de Nancy, Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Nancy

27. Service de Médecine Interne, Rothschild, Paris

28. Service de Médecine Interne et Immunologie Clinique Groupe Hospitalier UNEOS Metz-Vantoux

29. Service de Médecine Interne et Immunologie Clinique, Université Dijon, Hôpital Dijon, Dijon

30. Service de Pédiatrie et Immunologie Clinique, Université Lyon, Hôpital Lyon, Lyon, France

31. Service de Médecine Interne CHU Hédi Chaker, Faculté de Médecine de Sfax, Route El Ain, Tunisie

32. Service de Médecine et d’Hématologie, Hopital Rochefort, Rochefort

33. Department of Internal Medicine and Clinical Immunology, CHRU Tours, University of Tours, Tours

34. Service de Médecine Interne et Immunologie Clinique, Hôpital Besancon, Besancon

35. Service de Médecine Interne, Hôpital de la Réunion, Réunion, France

36. Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan

37. IRCCS Centro Neurolesi ‘Bonino-Pulejo’, Ospedale Piemonte, Messina, Italy

38. Sorbonne Université, 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), Paris, France

Abstract

Abstract Objective To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). Methods A total of 209 patients with TAK [median age 29 years (interquartile range 7–62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. Results A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. Conclusion This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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