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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

Frontiers in Pharmacology. 2016;7 DOI 10.3389/fphar.2016.00380


Journal Homepage

Journal Title: Frontiers in Pharmacology

ISSN: 1663-9812 (Online)

Publisher: Frontiers Media S.A.

LCC Subject Category: Medicine: Therapeutics. Pharmacology

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML



Antonio Vitale (University of Siena)

Antonella Insalaco (Bambino Gesù Children's Hospital)

Paolo Sfriso (University of Padua)

Giuseppe Lopalco (University of Bari)

Giacomo Emmi (University of Florence)

Marco Cattalini (University of Brescia)

Raffaele Manna (Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli)

Rolando Cimaz (AOU Meyer)

Roberta Priori (Sapienza University of Rome)

Rosaria Talarico (University of Pisa)

Stefano Gentileschi (University of Siena)

Ginevra de Marchi (University of Udine)

Micol Frassi (University of Brescia)

Romina Gallizzi (University of Messina)

Alessandra Soriano (Azienda Ospedaliera ASMN)

Maria Alessio (University Federico II)

Daniele Cammelli (University of Florence)

Maria Cristina Maggio (University of Palermo)

Renzo Marcolongo (University of Padua)

Francesco La Torre (A. Perrino Hospital)

Claudia Fabiani (Humanitas Research Hospital)

Serena Colafrancesco (Sapienza University of Rome)

Francesca Ricci (University of Brescia)

Paola Galozzi (University of Padua)

Ombretta Viapiana (University of Verona)

Elena Verrecchia (Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli)

Manuela Pardeo (Bambino Gesù Children's Hospital)

Lucia Cerrito (Università Cattolica Sacro Cuore)

Elena Cavallaro (University of Udine)

Alma Nunzia Olivieri (Seconda Università degli Studi of Naples)

Giuseppe Paolazzi (Santa Chiara Hospital)

Gianfranco Vitiello (University of Florence)

Armin Maier (Ospedale di Bolzano)

Elena Silvestri (University of Florence)

Chiara Stagnaro (University of Pisa)

Guido Valesini (Sapienza University of Rome)

Marta Mosca (University of Pisa)

Salvatore de Vita (University of Udine)

Angela Tincani (University of Brescia)

Giovanni Lapadula (University of Bari)

Bruno Frediani (University of Siena)

Fabrizio De Benedetti (Bambino Gesù Children's Hospital)

Florenzo Iannone (University of Bari)

Leonardo Punzi (University of Padua)

Carlo Salvarani (Azienda Ospedaliera ASMN)

Mauro Galeazzi (University of Siena)

Donato Rigante (Università Cattolica Sacro Cuore)

Luca Cantarini (University of Siena)


Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 14 weeks


Abstract | Full Text

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: 526 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 were 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 antirheumatic drugs 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 to 4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150 mg every 8 weeks, 150 mg every 4 weeks and 150 mg 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.