AUTHOR=Vitale Antonio , Insalaco Antonella , Sfriso Paolo , Lopalco Giuseppe , Emmi Giacomo , Cattalini Marco , Manna Raffaele , Cimaz Rolando , Priori Roberta , Talarico Rosaria , Gentileschi Stefano , de Marchi Ginevra , Frassi Micol , Gallizzi Romina , Soriano Alessandra , Alessio Maria , Cammelli Daniele , Maggio Maria C. , Marcolongo Renzo , La Torre Francesco , Fabiani Claudia , Colafrancesco Serena , Ricci Francesca , Galozzi Paola , Viapiana Ombretta , Verrecchia Elena , Pardeo Manuela , Cerrito Lucia , Cavallaro Elena , Olivieri Alma N. , Paolazzi Giuseppe , Vitiello Gianfranco , Maier Armin , Silvestri Elena , Stagnaro Chiara , Valesini Guido , Mosca Marta , de Vita Salvatore , Tincani Angela , Lapadula Giovanni , Frediani Bruno , De Benedetti Fabrizio , Iannone Florenzo , Punzi Leonardo , Salvarani Carlo , Galeazzi Mauro , Rigante Donato , Cantarini Luca 

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00380

DOI=10.3389/fphar.2016.00380

ISSN=1663-9812

ABSTRACT=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.