Frontiers in Pharmacology (Oct 2016)

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

  • Antonio Vitale,
  • Antonella Insalaco,
  • Paolo Sfriso,
  • Giuseppe Lopalco,
  • Giacomo Emmi,
  • Marco Cattalini,
  • Raffaele Manna,
  • Rolando Cimaz,
  • Roberta Priori,
  • Rosaria Talarico,
  • Stefano Gentileschi,
  • Ginevra de Marchi,
  • Micol Frassi,
  • Romina Gallizzi,
  • Alessandra Soriano,
  • Maria Alessio,
  • Daniele Cammelli,
  • Maria Cristina Maggio,
  • 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,
  • Donato Rigante,
  • Luca Cantarini

DOI
https://doi.org/10.3389/fphar.2016.00380
Journal volume & issue
Vol. 7

Abstract

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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.

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