Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study

  • Jurgen Sota
  • Antonio Vitale
  • Antonella Insalaco
  • Paolo Sfriso
  • Giuseppe Lopalco
  • Giacomo Emmi
  • Marco Cattalini
  • Raffaele Manna
  • Rolando Cimaz
  • Roberta Priori
  • Rosaria Talarico
  • Ginevra de Marchi
  • Micol Frassi
  • Romina Gallizzi
  • Alessandra Soriano
  • Maria Alessio
  • Daniele Cammelli
  • Maria Cristina Maggio
  • Stefano Gentileschi
  • Renzo Marcolongo
  • Francesco La Torre
  • Claudia Fabiani
  • Serena Colafrancesco
  • Francesca Ricci
  • Paola Galozzi
  • Ombretta Viapiana
  • Elena Verrecchia
  • Manuela Pardeo
  • Lucia Cerrito
  • Elena Cavallaro
  • Alma Nunzia Olivieri
  • Giuseppe Paolazzi
  • Gianfranco Vitiello
  • Armin Maier
  • Elena Silvestri
  • Chiara Stagnaro
  • Guido Valesini
  • Marta Mosca
  • Salvatore de Vita
  • Angela Tincani
  • Giovanni Lapadula
  • Bruno Frediani
  • Fabrizio De Benedetti
  • Florenzo Iannone
  • Leonardo Punzi
  • Carlo Salvarani
  • Mauro Galeazzi
  • Rossella Angotti
  • Mario Messina
  • Gian Marco Tosi
  • Donato Rigante
  • Luca Cantarini
  • for the “Working Group” of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology)
Original Article
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Abstract

A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (p = 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (p = 0.055), but a significant difference was observed when injection site reactions were excluded from AE (p = 0.01). No differences were identified in relation to gender (p = 0.462), different lines of biologic therapy (p = 0.775), and different dosages (p = 0.70 ANA; p = 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (p value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (p < 0.0001 ANA; p > 0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 [C.I. 0.250–0.638], p = 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.

Keywords

Anakinra Autoinflammatory disorders Canakinumab Interleukin-1 Safety profile 

Notes

Compliance with ethical standards

Conflict of interest

Luca Cantarini received grants/research support and speaker bureau from Novartis Pharma and SOBI. All of the other authors have nothing to disclose.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Jurgen Sota
    • 1
  • Antonio Vitale
    • 1
  • Antonella Insalaco
    • 2
  • Paolo Sfriso
    • 3
  • Giuseppe Lopalco
    • 4
  • Giacomo Emmi
    • 5
  • Marco Cattalini
    • 6
  • Raffaele Manna
    • 7
  • Rolando Cimaz
    • 8
  • Roberta Priori
    • 9
  • Rosaria Talarico
    • 10
  • Ginevra de Marchi
    • 11
  • Micol Frassi
    • 12
  • Romina Gallizzi
    • 13
  • Alessandra Soriano
    • 14
  • Maria Alessio
    • 15
  • Daniele Cammelli
    • 16
  • Maria Cristina Maggio
    • 17
  • Stefano Gentileschi
    • 1
  • Renzo Marcolongo
    • 18
  • Francesco La Torre
    • 19
  • Claudia Fabiani
    • 20
    • 21
  • Serena Colafrancesco
    • 5
  • Francesca Ricci
    • 6
  • Paola Galozzi
    • 3
  • Ombretta Viapiana
    • 22
  • Elena Verrecchia
    • 7
  • Manuela Pardeo
    • 2
  • Lucia Cerrito
    • 7
  • Elena Cavallaro
    • 11
  • Alma Nunzia Olivieri
    • 23
  • Giuseppe Paolazzi
    • 24
  • Gianfranco Vitiello
    • 16
  • Armin Maier
    • 25
  • Elena Silvestri
    • 5
  • Chiara Stagnaro
    • 10
  • Guido Valesini
    • 5
  • Marta Mosca
    • 10
  • Salvatore de Vita
    • 11
  • Angela Tincani
    • 12
  • Giovanni Lapadula
    • 4
  • Bruno Frediani
    • 1
  • Fabrizio De Benedetti
    • 2
  • Florenzo Iannone
    • 4
  • Leonardo Punzi
    • 3
  • Carlo Salvarani
    • 14
  • Mauro Galeazzi
    • 1
  • Rossella Angotti
    • 26
  • Mario Messina
    • 26
  • Gian Marco Tosi
    • 21
  • Donato Rigante
    • 27
  • Luca Cantarini
    • 1
  • for the “Working Group” of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology)
  1. 1.Research Center of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences, Surgery and Neurosciences, Rheumatology UnitUniversity of SienaSienaItaly
  2. 2.Division of Rheumatology, Department of Pediatric Medicine, IRCCSBambino Gesù Children’s HospitalRomeItaly
  3. 3.Rheumatology Unit, Department of MedicineUniversity of PaduaPaduaItaly
  4. 4.Interdisciplinary Department of Medicine, Rheumatology UnitUniversity of BariBariItaly
  5. 5.Department of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
  6. 6.Pediatric ClinicUniversity of Brescia and Spedali Civili di BresciaBresciaItaly
  7. 7.Institute of Internal Medicine, Periodic Fever Research Center, Fondazione Policlinico A. GemelliUniversità Cattolica Sacro CuoreRomeItaly
  8. 8.Pediatric Rheumatology UnitAOU MeyerFlorenceItaly
  9. 9.Department of Internal Medicine and Medical Specialties, Rheumatology UnitSapienza University of RomeRomeItaly
  10. 10.Rheumatology Unit, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  11. 11.Department of Medical and Biological Sciences, Rheumatology ClinicUniversity of UdineUdineItaly
  12. 12.Rheumatology and Clinical Immunology, Spedali Civili, and Department of Clinical and Experimental SciencesUniversity of BresciaBresciaItaly
  13. 13.Department of Pediatrics, Azienda G. MartinoUniversity of MessinaMessinaItaly
  14. 14.Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMNIstituto di Ricovero e Cura a Carattere ScientificoReggio EmiliaItaly
  15. 15.University Federico IINaplesItaly
  16. 16.Experimental and Clinical Medicine DepartmentUniversity of FlorenceFlorenceItaly
  17. 17.Universitary Department “Pro.S.A.M.I.”University of PalermoPalermoItaly
  18. 18.Clinical Immunology, Department of MedicineUniversity of PaduaPaduaItaly
  19. 19.Pediatric Rheumatology Section, Pediatric Oncoematology UnitVito Fazzi HospitalLecceItaly
  20. 20.Department of OphthalmologyHumanitas Research HospitalMilanItaly
  21. 21.Ophthalmology Unit, Department of Medicine, Surgery and NeuroscienceUniversity of SienaSienaItaly
  22. 22.Rheumatology Section, Department of MedicineUniversity of VeronaVeronaItaly
  23. 23.Dipartimento della Donna, del Bambino e di Chirurgia Generale e SpecialisticaSeconda Università degli Studi of NaplesNaplesItaly
  24. 24.Department of RheumatologySanta Chiara HospitalTrentoItaly
  25. 25.Struttura Semplice di ReumatologiaOspedale di BolzanoBolzanoItaly
  26. 26.Division of Pediatric Surgery, Department of Medical, Surgical and Neurological SciencesUniversity of SienaSienaItaly
  27. 27.Institute of Pediatrics, Periodic Fever Research Center, Fondazione Policlinico A. GemelliUniversità Cattolica Sacro CuoreRomeItaly

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