A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study.
Background:Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis.Objectives:To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults.Methods:We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016.Results:Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively).Conclusions:IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena Siena, Italy.
Antonio
A
Vitale
Division of Rheumatology, Department of Pediatric Medicine, IRCCS, Bambino Gesù Children's Hospital Rome, Italy.
Antonella
A
Insalaco
Rheumatology Unit, Department of Medicine, University of Padua Padua, Italy.
Paolo
P
Sfriso
Rheumatology Unit, Interdisciplinary Department of Medicine, University of Bari Bari, Italy.
Giuseppe
G
Lopalco
Department of Experimental and Clinical Medicine, University of Florence Florence, Italy.
Giacomo
G
Emmi
Pediatric Clinic, University of Brescia and Spedali Civili di Brescia Brescia, Italy.
Marco
M
Cattalini
Periodic Fever Research Center, Institute of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli Rome, Italy.
Raffaele
R
Manna
Pediatric Rheumatology Unit, AOU Meyer Florence, Italy.
Rolando
R
Cimaz
Department of Internal Medicine and Medical Specialities, Rheumatology Unit, Sapienza University of Rome Rome, Italy.
Roberta
R
Priori
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa Pisa, Italy.
Rosaria
R
Talarico
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena Siena, Italy.
Stefano
S
Gentileschi
Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine Udine, Italy.
Ginevra
G
de Marchi
Rheumatology and Clinical Immunology, Spedali Civili, and Department of Clinical and Experimental Sciences, University of Brescia Brescia, Italy.
Micol
M
Frassi
Department of Pediatrics, Azienda G. Martino, University of Messina Messina, Italy.
Romina
R
Gallizzi
Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico Reggio Emilia, Italy.
Alessandra
A
Soriano
Department of Pediatrics, University Federico II of Naples Naples, Italy.
Maria
M
Alessio
Rheumatology Section, Immunoallergology Unit, AOU Careggi Florence, Italy.
Daniele
D
Cammelli
Universitary Department "Pro.S.A.M.I.", University of Palermo Palermo, Italy.
Maria C
MC
Maggio
Clinical Immunology, Department of Medicine, University of Padua Padua, Italy.
Renzo
R
Marcolongo
Department of Pediatrics, A. Perrino Hospital Brindisi, Italy.
Francesco
F
La Torre
Department of Ophthalmology, Humanitas Research Hospital Milan, Italy.
Claudia
C
Fabiani
Department of Internal Medicine and Medical Specialities, Rheumatology Unit, Sapienza University of Rome Rome, Italy.
Serena
S
Colafrancesco
Pediatric Clinic, University of Brescia and Spedali Civili di Brescia Brescia, Italy.
Francesca
F
Ricci
Rheumatology Unit, Department of Medicine, University of Padua Padua, Italy.
Paola
P
Galozzi
Rheumatology Section, Department of Medicine, University of Verona Verona, Italy.
Ombretta
O
Viapiana
Periodic Fever Research Center, Institute of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli Rome, Italy.
Elena
E
Verrecchia
Division of Rheumatology, Department of Pediatric Medicine, IRCCS, Bambino Gesù Children's Hospital Rome, Italy.
Manuela
M
Pardeo
Periodic Fever Research Center, Institute of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli Rome, Italy.
Lucia
L
Cerrito
Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine Udine, Italy.
Elena
E
Cavallaro
Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Seconda Università degli Studi of Naples Naples, Italy.
Alma N
AN
Olivieri
Department of Rheumatology, Santa Chiara Hospital Trento, Italy.
Giuseppe
G
Paolazzi
Experimental and Clinical Medicine Department, University of Florence Florence, Italy.
Gianfranco
G
Vitiello
Struttura Semplice di Reumatologia, Ospedale di Bolzano Bolzano, Italy.
Armin
A
Maier
Department of Experimental and Clinical Medicine, University of Florence Florence, Italy.
Elena
E
Silvestri
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa Pisa, Italy.
Chiara
C
Stagnaro
Department of Internal Medicine and Medical Specialities, Rheumatology Unit, Sapienza University of Rome Rome, Italy.
Guido
G
Valesini
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa Pisa, Italy.
Marta
M
Mosca
Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine Udine, Italy.
Salvatore
S
de Vita
Rheumatology and Clinical Immunology, Spedali Civili, and Department of Clinical and Experimental Sciences, University of Brescia Brescia, Italy.
Angela
A
Tincani
Rheumatology Unit, Interdisciplinary Department of Medicine, University of Bari Bari, Italy.
Giovanni
G
Lapadula
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena Siena, Italy.
Bruno
B
Frediani
Division of Rheumatology, Department of Pediatric Medicine, IRCCS, Bambino Gesù Children's Hospital Rome, Italy.
Fabrizio
F
De Benedetti
Rheumatology Unit, Interdisciplinary Department of Medicine, University of Bari Bari, Italy.
Florenzo
F
Iannone
Rheumatology Unit, Department of Medicine, University of Padua Padua, Italy.
Leonardo
L
Punzi
Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico Reggio Emilia, Italy.
Carlo
C
Salvarani
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena Siena, Italy.
Mauro
M
Galeazzi
Periodic Fever Research Center, Institute of Pediatrics, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli Rome, Italy.
Donato
D
Rigante
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena Siena, Italy.
Luca
L
Cantarini
anakinra; autoinflammatory disorders; canakinumab; interleukin (IL)-1; treatment